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abstract: Background Alcohol dependence comorbid with major depressive disorder poses a major challenge in the clinical setting . The results in the treatment with selective serotonin re-uptake inhibitors have been conflicting . Thus , we compared in alcohol-dependent patients with co-morbid major depressive disorder the selective serotonin re-uptake inhibitor escitalopram to a compound that acts on different transporter system and may reduce craving , the glutamate receptor antagonist memantine . Methods Eighty alcohol-dependent patients comorbid with major depressive disorder in municipal alcohol clinics were r and omized 1:1 to receive memantine 20 mg or escitalopram 20 mg in a double-blind manner . During the 26-week study period patients continued their routine treatment at the clinics . Abstinence was not required but encouraged . The patients attended visits weekly during the first month , and then at 3 and at 6 months . Outcome measures were Alcohol Use Disorders Identification Test ( AUDIT ) , Obsessive Compulsive Drinking Scale ( OCDS ) and Drinking Diary . Results The completion rate was high in both groups , especially among the patients who had been abstinent at the beginning of the study . However , among those patients who were not abstinent at baseline , 47 % in both groups discontinued the study . Numbers of abstinent days were high in both groups throughout the study . Alcohol consumption measured by the AUDIT QF ( quantity-frequency ) score was significantly reduced in both groups , as was the craving for alcohol measured by the OCDS . Early age at first alcohol intoxication predicted poor treatment outcomes in patients treated with escitalopram , and the same was seen with the early onset of the first depressive episode . The same predictive effects were not found in patients treated with memantine . Conclusion Our results indicate that both memantine and escitalopram are useful adjunct medications for the treatment of alcohol dependence co-morbid with major depression . Memantine was at least as effective with regard to drinking as escitalopram . We believe that a direct comparison of memantine , with the commonly used escitalopram , can provide useful information for clinicians on the treatment of alcohol dependency co-morbid with MDD.Trial registration Clinical Trials.gov Identifier # Abstract The selective serotonin reuptake inhibitor citalopram was compared with clomipramine in a multicenter clinical study . From a total of 150 depressed patients ( age 18–65 years ) , 114 patients with a Hamilton Depression Scale ( HDS ) total score≧18 at the end of a 1 week placebo period were started on treatment with either citalopram ( 40 mg/day ) or clomipramine ( 150 mg/day ) ( fixed , single daily dose ) . Patients stratified according to diagnostic rating ( Newcastle Inventory , endogenous/non-endogenous ) were r and omly allocated to treatment groups using double blind principles . In total , 102 patients completed more than 2 weeks , treatment and were included in the analyses of therapeutic effect . The two drug groups were comparable in terms of sex , age , and departmental distribution . Categorical measurements of therapeutic effect based on the HDS total score showed that in the endogenously depressed patients a significantly higher percentage of patients on clomipramine ( n=37 ) than on citalopram ( n=38 ) were classified as complete responders ( HDS total≦7 ) after 3 , 4 and 5 weeks of treatment . In the non-endogenously depressed patients ( clomipramine : n=15 , citalopram : n=12 ) rather similar numerical differences were observed ( P<0.05 at 5th week ) . In the total patient group the percentage of complete response after 5 weeks was about 60 in the clomipramine group ( n=52 ) and about 30 in the citalopram group ( n=50 ) ( P<0.005 ) . The better effect of clomipramine seemed to be related in particular to the sleep items , but other items covering depression , retardation and anxiety/agitation also contributed to the difference in total score that was also seen in patients with low initial scores on the sleep items . Citalopram was devoid of the typical autonomic side effects and orthostatic hypotension seen with clomipramine . Symptoms of nausea/vomiting and headache became somewhat worse in the citalopram- and somewhat better in the clomipramine-treated patients . Participating centers:1Department of Psychiatry , Odense University Hospital , Odense , 2Department of Psychiatry , Rigshospitalet , University of Copenhagen , Copenhagen , 3Departments of Psychiatry , Frederiksborg General Hospital , Hillerød , 4Department A and C , Psychiatric University Hospital , Århus , 5Department of Psychiatry , Bornholm General Hospital , Rønne , 6Department of Clinical Pharmacology , Odense University , Odense Participating clinicians : J. And ersen2 , P. Bech2,3 , S. Benjaminsen1 , M. Bjerre1 , S. Bøjholm5 , P. Christensen1 , A. Gjerris2 , L. Hansted4 , E. Jensen3 , P. Kragh-Sørensen1 , C.B. Kristensen1,3 , P. Kyneb4 , D. Loldrup3 , O.F. Madsen4 , O.L. Pedersen1 , O.J. Rafaelsen2 , S. Rasmussen3 , N. Reisby4 , F. Sevaj3 , P. Simonsen4 , H.Y. Thomsen1 , P. Vestergaard4Coordination and drug assay : L.F. Gram6Statistical consultants : O. Aaskoven , P. Allerup Data - collection and -processing : C. Sánchez Steering Committee : P. Bech , L.F. Gram ( chairman ) , P. Kragh-Sørensen , O.J. Rafaelsen , N. Reisby , P. CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data BACKGROUND Major depression is highly recurrent . Antidepressant maintenance treatment has proven efficacy against recurrent depression . AIMS Comparison of prophylactic efficacy of citalopram versus placebo in unipolar , recurrent depression . METHODS Patients 18 - 65 years of age with recurrent unipolar major depression ( DSM-IV ) , a Montgomery-Asberg Depression Rating Scale score of > or = 22 and two or more previous depressive episodes , one within the past 5 years , were treated openly with citalopram ( 20 - 60 mg ) for 6 - 9 weeks and , if responding , continued for 16 weeks before being r and omised to double-blind maintenance treatment with citalopram or placebo for 48 - 77 weeks . RESULTS A total of 427 patients entered acute treatment and 269 were r and omised to double-blind treatment .  Time to recurrence was longer in patients taking citalopram than in patients taking placebo ( P:<0.001 ) . Prophylactic treatment was well tolerated . CONCLUSIONS Citalopram ( 20 , 40 and 60 mg ) is effective in the prevention of depressive recurrences .  Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase Anecdotal and published case reports suggest that some patients taking selective serotonin reuptake inhibitors ( SSRI )  experience diminution in emotional responsiveness . This study aims to define the individual components of emotion disturbed in these patients . Fifteen patients reporting SSRI-induced sexual dysfunction completed the Laukes Emotional Intensity Scale  ( LEIS ) , a question naire about various emotions . Compared to controls , patients reported significantly ( p<0.05 ) less ability to cry , irritation , care about others ' feelings , sadness , erotic dreaming , creativity , surprise , anger , expression of their feelings , worry over things or situations , sexual pleasure , and interest in sex . Total score on the LEIS did not correlate with total score on the Hamilton Depression Rating Scale . In our sample , 80 % of patients with SSRI-induced sexual dysfunction also describe clinical ly significant blunting of several emotions . Emotional blunting may be an under-appreciated side-effect of SSRIs that may contribute to treatment non-compliance and /or reduced quality of life ABSTRACT — In a double‐blind trial , comprising 96 depressed patients , citalopram was compared with maprotiline . The trial period was 6 weeks with ratings ( MADRS , CGI ) and side effects recordings taking place at Weeks 0 , 1 , 2 , 4 , and 6 . Both drugs were administered as a single evening dose , 40 or 60 mg for citalopram , and 75 or 150 mg for maprotiline .  MADRS total scores and CGI scores showed a highly significant reduction in both groups with no significant difference between them , whether the groups were considered as a whole or whether they were subdivided into endogenously/non‐endogenously depressed or melancholic/non‐melancholic patients . Side effects were not significantly different , but the maprotiline group showed more anticholinergic side effects , whereas the citalopram group showed more nausea , increased sweating and headache . Two patients on maprotiline were withdrawn because of side effects ( hypotension and somnolence in the one case ; tremor and insomnia in the other ) . One patient in each group was withdrawn because of increased transaminases , the citalopram‐treated patient having increased values , however , already at baseline . Apart from this , no cardiovascular side effects and no pathological laboratory values related to treatment were observed . The authors conclude that citalopram is a safe antidepressant drug and as effective as maprotiline Selective serotonin reuptake inhibitors ( SSRIs ) have been reported to be useful in the treatment of  depression in patients with Parkinson 's disease ( PD ) . However , a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs . So far , no prospect i ve trial comparing the effects of different SSRIs in depressed patients with PD has been performed . The aim of the present study was to assess the effects of four SSRIs ( citalopram , fluoxetine , fluvoxamine , and sertraline ) on motor performance and their efficacy on depression in a group of patients with PD . Sixty-two consecutive nondemented , nonfluctuating , depressed patients with PD were included in four treatment groups ( 15 patiens received citalopram , 16 fluoxetine , 16 fluvoxamine , and 15 sertraline ) . The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Beck Depression Inventory , and Hamilton Depression Rating Scale at baseline and after 1 , 3 , and 6 months . Fifty-two patients completed the study .  UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied . A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs ( Beck and Hamilton scores improving;p < 0.05 according to an analysis of variance ) . Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD BACKGROUND Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters . We wished to investigate whether genetic variation could be used to target or personalise treatment , in a comparison of selective serotonin reuptake inhibitors ( SSRIs ) with noradrenaline reuptake inhibitors ( NARIs ) . AIMS To test the hypothesis that patients homozygous for the long ( insertion ) polymorphism of the serotonin transporter ( 5-HTTLPR ) have an increased response to SSRI antidepressants but not to NARI antidepressants . METHOD In an individually r and omised , parallel-group controlled trial , people meeting criteria for a depressive episode who were referred by their general practitioner were r and omised to receive either citalopram ( an SSRI ) or reboxetine ( an NARI ) . R and omisation was by means of a remote automated system accessed by telephone . The main outcome was depressive symptoms , measured by Beck Depression Inventory ( BDI ) total score 6 weeks after r and omisation . The trial was registered with the International St and ard R and omised Controlled Trials Number registry ( IS RCT N31345163 ) . RESULTS Altogether 298 participants were r and omised to receive citalopram and 303 were r and omised to reboxetine . At 6 weeks follow-up , complete data were available for 258 participants taking citalopram and 262 taking reboxetine . We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment . The interaction term for BDI score at 6 weeks was 0.50 ( 95 % CI -2.04 to 3.03 , P = 0.70 ) , which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype . CONCLUSIONS It is unlikely that the 5-HTTLPR polymorphism alone will be clinical ly useful in predicting response to antidepressants in people with depression Objective : The presence of co-morbid depressive symptoms may have a negative impact on the management of diabetes mellitus . Moreover , some antidepressants may adversely affect glycemic control . Selective serotonin reuptake inhibitors ( SSRIs ) may improve glycemic control and may be beneficial for patients with co-morbid depression and diabetes . We examined the safety and efficacy of s-citalopram therapy in patients with co-morbid depression and diabetes , and its ability to improve glycemic control . Research Design and Methods : 17 patients were enrolled into the trial and 14 patients received open-label s-citalopram therapy for up to 16 weeks . Clinical outcome measures included the 17-item Hamilton depression rating ( HAM-D 17 ) and the clinical global impressions severity ( CGI/S ) and change ( CGI/C ) ratings . In addition , fasting glucose , fructosamine , and glycosylated hemoglobin-A1C measures were obtained before and during s-citalopram therapy . Results : We observed a significant reduction in mean HAM-D 17 ( p < 0.001 ) , CGI/S ( p = 0.001 ) and CGI/C ( p = 0.001 ) ratings during s-citalopram therapy . We also observed a modest , non-significant reduction in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during s-citalopram therapy . Limitation : Limitations of this study include a modest patient sample size and a 16-week treatment duration which may have been insufficient to demonstrate the full effect of SSRI therapy on glycemic control . Conclusion : We observed a significant reduction in depressive symptoms and modest , non-significant reductions in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during SSRI therapy of co-morbid depression and diabetes OBJECTIVE The aim of the study was to evaluate possible new treatments for major depressive disorder in patients with comorbid alcohol dependence in a municipal alcohol treatment unit . The efficacy of memantine , a noncompetitive glutamate N-methyl-D-aspartate (NMDA)-receptor blocker used for the treatment of moderate to severe Alzheimer 's disease , was compared with that of escitalopram , a selective serotonin reuptake inhibitor antidepressant . METHOD Eighty alcohol-dependent out patients with major depressive disorder ( DSM-IV criteria ) seeking treatment from municipal alcohol treatment clinics in Helsinki , Finl and , were r and omly assigned 1:1 to receive memantine 20 mg/day or escitalopram 20 mg/day . During the study period , patients continued their routine treatment at the clinics . Abstinence was not required . Concomitant interventions or imposed treatment goals were not offered by the study physician . The patients returned to the treatment clinics at weeks 1 , 2 , 4 , 12 , and 26 for data collection and for medication checking and dispensing . Outcome measures were the Montgomery-Asberg Depression Rating Scale ( MADRS ) and Beck Depression Inventory-II for depression , Hamilton Rating Scale for Anxiety ( HAM-A ) and Beck Anxiety Inventory for anxiety , Consortium to Establish a Registry for Alzheimer 's Disease test battery for cognitive functions , and Social and Occupational Functioning Assessment Scale for social and occupational functions and quality -of-life measures .  Twenty-nine patients in each group completed the study . All primary and secondary outcome statistical analyses were performed by an independent source for intent-to-treat population s , which included all patients r and omly assigned to treatment . The study was conducted from December 2004 to May 2006 . RESULTS Both treatments significantly reduced the baseline level of depression and anxiety according to MADRS and HAM-A , which were the primary measures ( p < .0001 ) . There was no significant difference between the memantine and escitalopram groups . Assessed cognitive functioning scores were primarily within the normative range and were unchanged in both groups . Quality -of-life outcomes equally improved in both treatment groups . CONCLUSIONS These data provide new evidence for the safety and potential efficacy of memantine and escitalopram for major depressive disorder in patients with comorbid alcohol dependence . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00368862 ABSTRACT Objective : The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives . In this study , quetiapine was compared with lithium in the augmentation of treatment-resistant depression . Research design and methods : Open-label , comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose . Patients were r and omised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications . Lithium was initiated at 600 mg/day ; quetiapine was titrated to 400 mg by day 7 . Results : Depression , measured by the Hamilton Depression Rating Scale ( HAM‑D ) , significantly improved from baseline in both quetiapine ( F1,90 = 25.11 , p < 0.0001 ) and lithium ( F1,90 = 34.54 , p < 0.0001 ) . The difference in improvement between the two groups began at day 14 and was seen at all timepoints thereafter ( p < 0.05 ) , with the quetiapine group showing greater improvement than the lithium group . In the Montgomery – Asberg Depression Rating Scale ( MADRS ) analysis , the difference between the quetiapine and lithium group was significant from day 28 onwards ( p < 0.05 ) , with subjects improving more in the quetiapine group than the lithium group . The treatment by week interaction showed a significant difference overall between the two groups ( p < 0.0001 ) . The severity of psychomotor retardation showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine ( p < 0.0001 ) and lithium ( p < 0.0001 ) groups . Conclusions : In this pilot study , quetiapine was an effective augmenting agent in treatment-resistant depression BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy The two diagnostic Newcastle Scales for depression have been evaluated in a drug trial with  antidepressants .  By use of latent structure analysis ( Rasch models ) it was found that two dimensions are necessary for describing the diagnosis of depression , one for endogenous features and one for reactive features . Of the depressed patients 50 % had a pure endogenous depression , 14 % had a pure reactive depression , 32 % had mixed endogenous and reactive depression , and 4 % had uncertain diagnosis . In the pure endogenous depression group 77 % had a monotonically non-decreasing improvement curve during treatment whereas in the other diagnostic categories around 50 % had such an improvement Background Selective serotonin reuptake inhibitors ( SSRIs ) are popular medications for anxiety and depression , but their effectiveness , particularly in patients with prominent symptoms of loss of motivation and pleasure , has been question ed . There are few studies of the effect of SSRIs on neural reward mechanisms in humans . Methods We studied 45 healthy participants who were r and omly allocated to receive the SSRI citalopram , the noradrenaline reuptake inhibitor reboxetine , or placebo for 7 days in a double-blind , parallel group design . We used functional magnetic resonance imaging to measure the neural response to rewarding ( sight and /or flavor of chocolate ) and aversive stimuli ( sight of moldy strawberries and /or an unpleasant strawberry taste ) on the final day of drug treatment . Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex . In contrast , reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward . Citalopram also decreased neural responses to the aversive stimuli conditions in key “ punishment ” areas such as the lateral orbitofrontal cortex . Reboxetine produced a similar , although weaker effect . Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli . The ability of SSRIs to decrease neural responses to reward might underlie the question ed efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment OBJECTIVE The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment . The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs . METHOD High- quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram ( N=394 ) or nortriptyline ( N=312 ) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) project , a partially r and omized open-label pharmacogenetic trial . RESULTS Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association . Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline . Response to escitalopram was best predicted by a marker in the interleukin-11 ( IL11 ) gene . A set of 72 a priori-selected c and i date genes did not show pharmacogenetic associations above a chance level , but an association with response to escitalopram was detected in the interleukin-6 gene , which is a close homologue of IL11 . CONCLUSIONS While limited statistical power means that a number of true associations may have been missed , these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional c and i date s. Genome-wide studies , if properly replicated , may thus be important steps in the elucidation of the genetic basis of pharmacological response OBJECTIVE The authors hypothesized that age would moderate the response of patients with schizophrenia and subsyndromal depression ( SSD ) treated citalopram with depressive symptoms and other outcomes . Also , older patients would exhibit more side effects with citalopram . METHODS Participants of 40 years or older had schizophrenia or schizoaffective disorder with SSD . Patients r and omly received flexible dosing of citalopram or placebo augmentation of their antipsychotic medication . Linear regression determined whether age had any moderating effect on depressive symptoms , global psychopathology , negative symptoms , mental functioning , and quality of life . Age-related side effects were examined . RESULTS There were no significant drug group by age interaction in depressive or psychotic symptoms , mental Short Form-12 , or quality of life scores . Similarly , there were few age-related side effect differences . CONCLUSION Symptoms in younger and older patients with schizophrenia and SSD treated with citalopram seem to respond similarly . Adverse events do not seem to differ with age BACKGROUND Major depressive disorder is a recurrent illness that often requires maintenance antidepressant treatment . Escitalopram is a selective serotonin reuptake inhibitor ( SSRI ) that has shown efficacy in both acute and continuation treatment of major depressive disorder . The current trial examined the efficacy of maintenance escitalopram treatment in preventing depression recurrence in patients who responded to acute SSRI therapy . METHOD Patients with recurrent DSM-IV-defined major depressive disorder ( > or= 2 previous episodes ; baseline Montgomery-Asberg Depression Rating Scale [ MADRS ] score > or= 22 ) who had responded ( MADRS score < or= 12 ) to acute open-label treatment ( 8 weeks ) with 1 of 4 SSRIs ( fluoxetine , sertraline , paroxetine , or citalopram )  received open-label , flexible-dose continuation treatment ( 16 weeks ) with escitalopram ( 10 - 20 mg/day ) . At the end of continuation treatment , patients maintaining response criteria were r and omly assigned to 52 weeks of double-blind , fixed-dose maintenance treatment with escitalopram ( 10 or 20 mg/day ) or placebo .  Recurrence was defined as a MADRS score > or= 22 or insufficient therapeutic response during the double-blind phase . The study was conducted between October 16 , 2000 , and February 4 , 2003 . RESULTS A total of 234 patients who responded to acute open-label treatment with 1 of 4 SSRIs received at least 1 dose of open-label escitalopram continuation treatment . Of 164 patients who completed escitalopram continuation treatment , 139 were r and omly assigned to double-blind maintenance treatment with escitalopram ( N = 73 ) or placebo ( N = 66 ) . Mean baseline MADRS scores at the start of the maintenance phase were < 5 for both the placebo- and escitalopram-treatment groups . Time to recurrence was significantly longer in patients who received maintenance treatment with escitalopram compared with patients switched to placebo ( hazard ratio = 0.26 , 95 % CI = 0.13 to 0.52 , p < .001 ) . Long-term escitalopram treatment was well tolerated . CONCLUSION Maintenance treatment with escitalopram was well tolerated and significantly reduced the risk for recurrence of depression . Patients with few residual symptoms following continuation treatment with escitalopram experienced a high rate of depression recurrence when switched to placebo , demonstrating the need for maintenance therapy of recurrent major depressive disorder beyond 4 to 6 months of initial symptom resolution even if few residual symptoms are present The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram , in effects on sexual function and satisfaction . The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre r and omized controlled trial of acute treatment of patients with DSM-IV major depression . Patients were r and omly assigned to receive reboxetine ( 4 mg b.d . ) or paroxetine ( 20 mg mane ) using a double-dummy technique to preserve the blind . The dosage could be increased at day 28 ( to reboxetine 4 mg mane , 6 mg nocte ; or paroxetine 20 mg b.d . ) . Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and Clinical Global Impression Scale for Severity ( CGI-S ) at all study visits , and the Clinical Global Impression of Improvement ( CGI-I ) at each visit after r and omization . Sexual function and satisfaction was assessed by visual analogue scale ( VAS ) items of the Rush Sexual Inventory completed at baseline and days 28 and 56 . There were no significant differences between groups in demographic or clinical features at baseline . There was a gradual reduction in severity of depressive symptoms  ( reboxetine , 14.3 ; paroxetine , 12.0 : observed case analysis ) , with no significant differences between groups . There were significant differences ( p 0.05 ) , with advantages for reboxetine , at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited , and non-significant trends with advantages for reboxetine , in frequency of sexual thoughts at Week 4 ( p 0.05 ) and Week 8 ( p 0.08 ) ; and in desire to initiate sexual activity at Week 4 ( p 0.09 ) . Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study ( n 10 ) reduced the statistical significance of the findings , although there were still numerical advantages for reboxetine .  Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine , but this improvement is greater and more rapid with reboxetine BACKGROUND : Severe depression is associated with an extensive economic burden on both the patient and society . OBJECTIVE : To estimate the cost-effectiveness in Austria of escitalopram compared with citalopram in the management of severe depression ( Montgomery — Åsberg Depression Rating Scale score ≥30 ) . METHODS : A decision model incorporated treatment paths and associated direct re source use ( psychiatric hospitalization , medications , general practitioner and psychiatrist visits , treatment discontinuation , suicide attempts ) associated with managing severe depression and the indirect cost of work absenteeism over a 6-month period . Main outcomes were clinical success ( remission at 6 mo ) and cost ( 2002 Euros equals ∼1.25 US ) of treatment . The analysis was performed from the Austrian societal and Social Healthcare Insurance System ( SHIS ) perspectives . Clinical input data were derived from a meta- analysis of 8-week r and omized clinical trials . Costs were derived from st and ard Austrian price lists or from the literature . RESULTS : Six months after the start of treatment , the overall clinical success remission rate was higher for escitalopram ( 53.7 % ) than for citalopram ( 48.7 % ) . From the SHIS perspective , the total expected cost per successfully treated severely depressed patient was € 924 ( 32.1 % ) lower for escitalopram ( € 2879 ) compared with citalopram ( € 3803 ) . From the societal perspective , the total expected cost per successfully treated severely depressed patient was € 1369 ( 24.4 % ) lower for escitalopram ( € 5610 ) than for citalopram ( € 6979 ) . Sensitivity analyses demonstrated that the model was robust and that , even if citalopram  had no acquisition  cost , escitalopram remained the dominant strategy for both perspectives . CONCLUSIONS : Treatment with escitalopram was the dominant strategy . These data suggest that escitalopram is a cost-effective antidepressant compared with citalopram in the management of severe depression in Austria Milnacipran is a new antidepressive drug , a combined noradrenaline/serotonin ( NA/5‐HT ) reuptake inhibitor , which has been suggested to be as effective as and better tolerated than tricyclic antidepressants . Since long‐term studies are lacking , we compared the efficacy , safety and tolerability of milnacipran and clomipramine in a double‐blind , r and omized , parallel‐group study setting during 26 weeks of treatment in patients with major depression . A total of 107 patients were treated with either milnacipran  ( n=52 ) or clomipramine ( n=55 ) . Due to active treatment of duration less than 12 days in four patients and protocol deviation in one patient , in total 47 milnacipran‐treated patients were eligible for efficacy analysis . Nine patients in the clomipramine group continued on active treatment for less than 12 days . Thus 46 clomipramine‐treated patients were finally included in the efficacy analysis . After 1 week of dose escalation , there was a fixed dosage regimen of either milnacipran ( 200 mg daily ) or clomipramine ( 150 mg daily ) during weeks 2 to 10 , followed by flexible dosing of milnacipran ( 100,150 or 200 mg daily ) or clomipramine ( 75 , 100 or 150 mg daily ) during weeks 11 to 26 . A total of 53 patients ( 49 % ) completed the 26‐week study period ; 21 % ( 11/52 ) of the patients in the milnacipran group and 38 % ( 21/55 ) of the patients in the clomipramine group discontinued their medication prematurely due to adverse events , whereas 19 % ( 10/52 ) of those on milnacipran and 7 % ( 4/55 ) of those on clomipramine treatment withdrew due to either lack of efficacy or clinical deterioration . The mean change ( ±SD ) in the Hamilton Depression Rating Scale ( HAMD ) score between the baseline and the last rating ranged from 23.7±3.1 to 12.0±9.5 in the milnacipran‐treated patients and from 23.1±3.5 to 8.0±8.5 in the clomipramine‐treated patients , revealing a significant difference in favour of clomipramine . In total 58 % of the milnacipran‐treated patients vs. 72 % of the clomipramine‐treated patients showed a ≥50 % reduction in their baseline HAMD scores and 45 % vs. 63 % had an HAMD score of ≤7 at the last rating , respectively . Moreover , the time to the onset of the antidepressant action ( defined as ≥50 % reduction of the baseline HAMD score ) showed a significant difference in favour of clomipramine . In addition , clomipramine was significantly more efficacious in patients with a baseline HAMD score of ≥24 as evidence d by the analysis of the HAMD score at week 6 and at the last rating . The Montgomery Åsberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression ( CGI ) scale did not show significant differences between the treatment groups . The safety analysis did not reveal any differences of clinical significance in cardiovascular variables between the study drugs . Dry mouth was significantly less frequently reported by the milnacipran‐treated patients during the early and later phases ( weeks 6 to 26 ) of the study , while insomnia was more common in the milnacipran group during weeks 1 to 6 . In conclusion , milnacipran appeared to be less effective  than clomipramine in the long‐term treatment of depression . The side‐effects of the drugs differed to a certain extent , and milnacipran tended to be somewhat better tolerated  than clomipramine BACKGROUND Milnacipran is a dual-action antidepressant which inhibits both serotonin and noradrenaline reuptake with no affinity for any neurotransmitter receptor studied . METHODS A 6-week double-blind multicentre study compared milnacipran ( 100 mg/day ) with paroxetine ( 20 mg/day ) in 300 out patients with major depression . Efficacy was evaluated using HAMD17 , MADRS and CGI for severity of illness and global improvement . Data were analysed on an intention to treat , last observation carried forward , basis . RESULTS Milnacipran and paroxetine were both effective and well tolerated with no significant difference in their effects . After treatment discontinuation , milnacipran was associated with significantly less emergent symptoms . Responders , at endpoint , to milnacipran had significantly greater levels of psychomotor retardation at baseline than non-responders . LIMITATIONS The study did not include a placebo group so that it is impossible to determine absolute levels of efficacy . CONCLUSIONS Both milnacipran and paroxetine were effective and well tolerated by out patients with major depression treated for 6 weeks . After treatment discontinuation milnacipran was associated with less emergent symptoms . Psychomotor retardation at baseline may be a predictive factor of a favourable response to milnacipran Serum sample s were selected r and omly from blood sample s drawn in the morning for other reasons in patients treated with citalopram  , and the serum concentrations of citalopram ( S-citalopram )  and its major metabolite desmethylcitalopram were determined . A total of 44 patients , 13 males and 31 females , with a median age of 38.5 years ( range 18 - 89 ) entered the study . In 17 patients given 20 mg/day of citalopram the S-citalopram was ( median and range ) 153 nmol/l ( 83 - 237 ) . In 24 patients treated with citalopram 40 mg/day the S-citalopram was 240 nmol/l ( range 0 - 360 ) . In one serum sample no S-citalopram could be detected ( non-compliance ) and in another sample S-citalopram was just above the detection limit ( about 3 nmol/l ) . The latter may at least partly be due to treatment with 600 mg/day of carbamazepine , which is known to accelerate the metabolism of other drugs . The serum concentration of the major metabolite desmethylcitalopram averaged 28 % of S-citalopram and is most likely without clinical importance . It is concluded that determination of S-citalopram may be considered if there is doubt about the compliance of the patient , in drug interaction cases or if the clinical effect is poor . If high A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders . In general , unipolar depression is connected with low blood zinc levels that are increased by effective antidepressant therapy . A placebo-controlled , double blind pilot study of zinc supplementation in antidepressant therapy was conducted in patients who fulfilled DSM IV criteria for major ( unipolar ) depression . Patients received zinc supplementation ( 6 patients ; 25 mg of  Zn2 + once daily ) or  placebo  ( 8 patients ) and were treated with st and ard antidepressant therapy ( tricyclic antidepressants , selective serotonin reuptake inhibitors ) . Hamilton Depression Rating Scale ( HDRS ) and Beck Depression Inventory ( BDI ) were used to assess efficacy of antidepressant therapy , and patients ' status was evaluated before the treatment and 2 , 6 and 12 weeks after its commencement . Antidepressant treatment significantly reduced HDRS scores by the 2nd week of treatment in both groups , and lowered BDI scores at the 6th week in zinc-treated group . Zinc supplementation significantly reduced scores in both measures after 6- and 12-week supplementation when compared with placebo treatment . This preliminary study is the first demonstration of the benefit of zinc supplementation in antidepressant therapy . The mechanism(s ) may be related to modulation of glutamatergic or immune systems by zinc ion OBJECTIVE To examine the effects of citalopram augmentation of antipsychotics on suicidal ideation in middle-aged and older people with schizophrenia and subthreshold depressive symptoms . METHOD In this placebo-controlled trial conducted from September 1 , 2001 , to August 31 , 2007 , 198 out patients > or = 40 years old with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and subthreshold depressive symptoms were r and omly assigned to flexible-dose citalopram ( n = 104 ) or placebo ( n = 94 ) augmentation of their antipsychotic for 12 weeks . Depression was measured with the Hamilton Depression Rating Scale ( HDRS ) and Calgary Depression Rating Scale ( CDRS ) . Primary suicidal ideation measures were the Clinical Global Impressions-Severity of Suicide scale ( CGI-SS ) and the InterSePT Scale for Suicidal Thinking ( ISST ) ; secondary outcomes were the Scale for Suicidal Ideation ( SSI ) , Beck Hopelessness Scale ( BHS ) , HDRS item 3 , and CDRS item 8 . RESULTS Compared to placebo , at the final visit , citalopram was associated with lower BHS scores ( 4.21 vs 4.98 ; P < .05 ) and lower likelihood of having suicidal ideation on the ISST ( 17.7 % vs 38.7 % ; P < .005 ) and HDRS item 3 ( 14.4 % vs 22.6 % ; P < .05 ) . Among the 114 participants with no baseline suicidal ideation , there were no significant differences between citalopram and placebo regarding " emergent " ideation on either primary outcome . Among the 55 participants with baseline suicidal ideation , fewer treated with citalopram had endpoint ideation on the ISST ( 28.6 % vs 66.7 % ; P < .05 ) . Significantly more depression responders than nonresponders went from having baseline suicidal ideation to no suicidal ideation on both the ISST ( 75.0 % vs 31.4 % ; P < .05 ) and CGI-SS ( 84.6 % vs 31.3 % ; P < .05 ) . CONCLUSIONS Treatment-emergent suicidal ideation was no more common with citalopram than placebo . In participants with baseline suicidal ideation , citalopram reduced suicidal ideation , especially in those whose depressive symptoms responded to treatment The objective of this study was to determine if combined psychotherapy and pharmacotherapy reduces reported depressive symptoms compared to an assessment only condition for active drug injectors over nine months . Using a r and omized controlled trial at an outpatient academic research office , the research ers applied psychotherapy ( eight sessions of cognitive behavioral therapy ) plus pharmacotherapy ( citalopram ) to active injection drug users with a DSM-IV diagnosis of major depression , dysthymia , substance-induced mood disorder with symptoms persisting for at least three months , or major depression plus dysthymia , and a Modified Hamilton Rating Scale for Depression ( MHRSD ) score greater than 13 . The MHRSD scale scores were then assessed at the completion of three , six , and nine months . Participants ( n = 109 ) were 64 % male and 82 % Caucasian , with a mean baseline MHRSD score of 20.7 . Depression subtypes included major depression only ( 63 % ) , substance-induced depression ( 17 % ) , and double-depression ( 17 % ) .  Study retention at nine months was 89 % . At the completion of three months of acute treatment , 26 % of combined treatment patients ( n = 53 ) , compared to 12 % of control patients ( n = 56 ) , were in remission ( p = .047 ) . At both six and nine months , the between-group differences in remission rates and mean MHRSD scores were insignificant , although the overall mean MHRSD score decreased from baseline ( p < .01 ) . At all follow-up assessment s , depression remission was significantly associated with lower heroin use . Among active drug injectors diagnosed with depression , symptoms decline over time . Combined treatment is superior to an assessment -only condition in depression remission rates at the end-of-treatment , but this difference does not persist The antidepressant efficacy and tolerability of milnacipran , a dual action serotonin-noradrenaline reuptake inhibitor , were compared with those of the selective serotonin reuptake inhibitor , fluvoxamine , in 113 patients with moderate to severe major depression . Treatment with milnacipran , 50 mg b.d . for 6 weeks , produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores than fluvoxamine , 100 mg b.d . ( P = 0.007 ; 65.4 % versus 49.9 % , respectively ) ; significantly greater decreases were also seen on days 7 ( P = 0.04 ) and 28 ( P = 0.03 ) . The response rate ( the proportion of patients showing a decrease in MADRS scores of at least 50 % ) was 78.9 % in patients receiving milnacipran , compared with 60.7 % in fluvoxamine-treated patients ( P = 0.04 ) . Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores ( P = 0.05 ) . On the Clinical Global Impression Improvement scale , 77.2 % of milnacipran-treated patients were rated as considerably or markedly improved , compared with 60.7 % of patients receiving fluvoxamine ( P = 0.06 chi-squared ) . Both treatments were well tolerated ; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine . It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors , such as fluvoxamine , in the treatment of moderate to severe major depression OBJECTIVE The aim of this study was to compare over 1 year the effect of sertraline and citalopram on depressive symptoms and cognitive functions of nondemented elderly patients with minor depressive disorder and subsyndromal depressive symptomatology . METHOD We recruited 138 consecutive non-demented out patients of either sex , aged > or = 65 years , who were classified as meeting research criteria for minor depressive disorder or sub-syndromal depressive symptomatology using the Structured Clinical Interview for DSM-IV . Subjects were assigned to receive citalopram 20 mg/day ( 66 patients ) or sertraline 50 mg/day ( 72 patients ) orally for 1 year . Patients were assessed at baseline and after 1 , 2 , 3 , and 6 months and at 1 year by raters masked with regard to patients ' treatment assignments . The Hamilton Rating Scale for Depression , the Geriatric Depression Scale , and the Global Assessment of Functioning were administered to assess the course of depressive symptoms and social functioning during the study . Cognitive measures included Trail Making Test-Parts A and B , Wechsler Memory Scale , Mini-Mental State Examination , and a verbal fluency test . Data were collected from March 2000 to March 2003 . RESULTS The overall completion rate was 72 % . Both treatments induced a significant , sustained , and comparable improvement in depressive symptoms and in social functioning . Nearly half of the subjects in the 2 groups achieved remitter status at study endpoint . Significant within-group improvements also were observed in all cognitive measures . Both drugs were well tolerated during the whole study period . CONCLUSION Our results suggest that sertraline and citalopram can improve depressive symptoms and cognitive functions of minor depressive disorder and subsyndromal depressive symptomatology in elderly nondemented patients SUMMARY The antidepressant efficacy and safety of milnacipran , a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline , was compared with that of the tricyclic antidepressant , imipramine , in a multi-centre , double-blind , r and omised , parallel group , comparative trial in 5 hospital centres in Spain . One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association ( third revision ) , with a minimum score of 25 on the Montgomery and Åsberg Depression Rating Scale were treated for 6 weeks with milnacipran ( 100 mg/day ) or imipramine ( 150 mg/day ) . Both treatments showed similar efficacy in reducing depressive symptoms . The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group , particularly those related to anticholinergic symptoms . Dysuria and shivering , however , were more common with milnacipran . The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day  ( n = 191 ) or placebo  ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated OBJECTIVE The use of atypical antipsychotics ( AAPs ) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated , and aripiprazole showed positive effects in the treatment of unipolar depression . However , no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet . METHODS In this prospect i ve , double-blind ,  placebo-controlled  , r and omized trial , 23 in patients with bipolar depression according to DSM-IV criteria were included . Before r and omization , patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week . After inclusion , all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks . The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale ( HDRS ) within 6 weeks . RESULTS After 6 weeks of treatment , the HDRS score decreased in both groups . There was no significant difference between both the groups at any point of time with respect to the HDRS . CONCLUSIONS Derived from this small pilot study , adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression . However , this lack of additional benefit seems to stem from the already good effectiveness of the control group , namely the treatment with citalopram In this multicenter study , the clinical efficacy of citalopram was investigated in 98 patients with moderate AD/SDAT or VD using a combined double-blind and open technique with placebo and citalopram . Analyses were made for each diagnosis after four weeks of double-blind treatment . Patients with AD/SDAT treated with citalopram showed a significant improvement in emotional bluntness , confusion , irritability , anxiety , fear/panic , depressed mood and restlessness . Those improvements were not found after treatment with placebo . There were no significant improvements in patients with VD . No improvements were recorded in motor or cognitive impairment .  Citalopram provoked few and comparatively mild side-effects . None of the changes observed during the double-blind withdrawal period were identified as withdrawal symptoms or rebound phenomena From theoretical and clinical perspectives , it is important to know if selected serotonin-reuptake inhibitors ( SSRIs ) , often administered concurrently with electroconvulsive therapy ( ECT ) , modify seizure duration . In a study with a double-blind , cross-over design , the authors evaluated the effect of citalopram , the most selective SSRI available , on the length of electrically induced seizures and on hormone secretion during ECT . Ten depressed women were given either 20 mg citalopram or placebo orally 2 hours before the third and fourth ECT sessions . Seizure duration was assessed by the cuff technique and from electroencephalographic recordings , whereas blood for prolactin , thyrotropin , and cortisol assessment was sample d before ECT and 5 , 10 , 20 , 30 , 40 , and 60 minutes after ECT . No adverse effects after the administration of citalopram were recorded . The length of seizures was not statistically different in the citalopram ( 29.3 ± 8.4 seconds ) and placebo sessions ( 28.2 ± 9.4 seconds ) . Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or placebo administration nor the patterns of ECT-induced hormone secretions differed between the two drug and placebo conditions . The lack of effect of citalopram on hormones in this study may be a result of possible deficiencies of the monoaminergic ( i.e. , serotoninergic ) systems in depression . Although safety and efficacy issues were not fully addressed by coadministering citalopram for the long term and throughout the course of ECT , these findings support the view that challenges the typical clinical practice of discontinuing SSRIs before ECT Current treatments for Obsessive Compulsive Disorder ( OCD ) rely primarily on serotonergic mechanisms . However , approximately 30 % of patients do not respond to serotonin reuptake inhibitors and remain chronically ill . Given the behavioral similarities between some of the compulsive behaviors in OCD and addiction , we hypothesized that the opioid antagonist naltrexone might attenuate compulsions in OCD as well . The effect of naltrexone augmentation to SRI was compared to placebo in 10 OCD out patients who had not responded to an adequate dose of SSRI or clomipramine for at least 2 months . Participants underwent 5 weeks of treatment with naltrexone or placebo ( and 1 week of tapering ) in a r and omized , double-blind , cross-over design . Patients were evaluated weekly using the Y-BOCS , CGI , HAM-A , and MADRS scales . A two-way repeated measures MANOVA revealed no significant effect for Y-BOCS . However , while receiving naltrexone , patients had significantly higher scores on CGI , MADRS and HAM-A as compared to placebo . The lack of significant findings on OC symptoms could be due to either ceiling effect or alternatively , due to a non-specific exacerbation on anxiety and depression but not on OC symptoms BACKGROUND Major depressive disorder ( MDD ) has been associated with alterations in immune function . Suppression of natural killer ( NK ) cell activity ( NKCA ) reliably characterizes immunological alterations observed in MDD . Antidepressant pharmacotherapy has been associated with modulation of NKCA . Previous investigations into antidepressant modulation of NKCA have not employed r and omized double-blind placebo controlled design s. Thus , it is unknown whether treatment-associated changes in immune function are due to drug , placebo , or spontaneous remission effects . The present investigation examined the effect of antidepressant treatment on NKCA utilizing a r and omized double-blind placebo controlled experimental design . METHOD Patients ( N = 16 ) met DSM-IV criteria for MDD and were r and omly assigned to drug ( N = 8 ; citalopram , 20 mg/day ) or placebo ( N = 8) under double-blind conditions . Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale ( HDRS ) . NK cell function was measured using a st and ard chromium-release assay and NK cell number assessed by flow cytometry . HDRS scores , NK cell function , and NK cell numbers were collected at 0 , 1 , 2 and 4 weeks of treatment . RESULTS Clinical response was associated with augmented NKCA independent of treatment condition . Failure to respond to treatment result ed in significantly reduced NKCA over treatment interval . CONCLUSIONS The present results suggest that alterations in the depressive syndrome , regardless of therapeutic modality , may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD The antidepressant selective serotonin transporter inhibitors ( SSRIs ) are clinical ly active after a delay of several weeks . Indeed , the rapid increase of serotonin ( 5-HT ) caused by SSRIs , stimulates the 5-HT(1A ) autoreceptors , which exert a negative feedback on the 5-HT neurotransmission . Only when autoreceptors are desensitized , can SSRIs exert their therapeutic activity . The 5-HT(1A ) receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback . Using the alpha-[(11)C]methyl-L-tryptophan/positron emission tomography ( PET ) , the goal of the present double-blind , r and omized study was to compare the changes in alpha-[(11)C]methyl-L-tryptophan trapping , an index of serotonin synthesis , in patients suffering from unipolar depression treated with the SSRI citalopram ( 20 mg/day ) plus placebo versus patients treated with citalopram plus pindol ( 7.5 mg/day ) .  PET and Hamilton depression rating scale ( HDRS-17 ) were performed at baseline , and after 10 and 24 days of antidepressant treatment . Results show that the combination citalopram plus pindol , compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex ( BA 9 ) . This research is the first human PET study demonstrating that , after 24 days , the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex , an area associated to depressive symptoms CONTEXT Depression occurs in more than half of patients who have experienced a stroke . Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality . Prevention of depression thus represents a potentially important goal . OBJECTIVE To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication . DESIGN , SETTING , AND PARTICIPANTS A multisite r and omized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9 , 2003 , to October 1 , 2007 . The 12-month trial included 3 groups : a double-blind placebo-controlled comparison of escitalopram ( n = 59 ) with placebo ( n = 58 ) , and a nonblinded problem-solving therapy group ( n = 59 ) . MAIN OUTCOME MEASURES The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) ( DSM-IV ) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression ( ie , research criteria ) . RESULTS Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram ( 11 major and 2 minor cases of depression [ 22.4 % ] vs 3 major and 2 minor cases of depression [ 8.5 % ] , adjusted hazard ratio [ HR ] , 4.5 ; 95 % confidence interval [ CI ] , 2.4 - 8.2 ; P < .001 ) and also more likely than individuals who received problem-solving therapy ( 5 major and 2 minor cases of depression [ 11.9 % ] , adjusted HR , 2.2 ; 95 % CI , 1.4 - 3.5 ; P < .001 ) . These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age , sex , treatment site , and severity of impairment in the model . Using an intention-to-treat conservative method of analyzing the data , which assumed that all 27 patients who did not start r and omized treatment would have developed depression , and controlling for prior history of mood disorders , escitalopram was superior to placebo ( 23.1 % vs 34.5 % ; adjusted HR , 2.2 ; 95 % CI , 1.2 - 3.9 ; P = .007 ) , while problem-solving therapy was not significantly better than placebo ( 30.5 % vs 34.5 % ; adjusted HR , 1.1 ; 95 % CI , 0.8 - 1.5 ; P = .51 ) . Adverse events , including all-cause hospitalizations , nausea , and adverse effects associated with escitalopram were not significantly different between the 3 groups . CONCLUSIONS In this study of nondepressed patients with recent stroke , the use of escitalopram or problem-solving therapy result ed in a significantly lower incidence of depression over 12 months of treatment compared with placebo , but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00071643 Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin ( Selective Serotonin Reuptake Inhibitors – SSRIs ) and noradrenaline ( Noradrenaline Reuptake Inhibitors – NaRIs ) into the presynaptic terminal . There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action . Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs , there are patients who respond to one class of compounds and not another . This suggests that treatment response could be predicted by genetic and /or clinical characteristics . Firstly , this study aims to investigate the influence of a polymorphism ( SLC6A4 ) in the 5HT transporter in altering response to SSRI medication . Secondly , the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs . Methods / design The GenPod trial is a multi-centre r and omised controlled trial . GPs referred patients aged between 18–74 years presenting with a new episode of depression , who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse . Patients were interviewed to ascertain their suitability for the study . Eligible participants ( with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory ( BDI ) score > 14 ) were r and omised to receive one of two antidepressant treatments , either the SSRI Citalopram or the NaRI Reboxetine , stratified according to severity . The final number r and omised to the trial was 601 . Follow-up assessment s took place at 2 , 6 and 12 weeks following r and omisation . Primary outcome was measured at 6 weeks by the BDI . Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments . Discussion The results of the trial will provide information about targeting antidepressant treatment for individual patients ; in turn this may increase prescribing efficacy , thereby speeding recovery and reducing the cost to the NHS . It will also help to underst and the different roles that noradrenaline and serotonin might play in the biology of depression . The trial is expected to report in the autumn of 2008.Trial Registration IS RCT N Many patients with major depressive disorder ( MDD ) present with concurrent substance use disorders ( SUDs ) , which has been thought to impair their response to antidepressants . Clinicians often delay antidepressant treatment until sustained sobriety has been established . Unfortunately , these comorbid subjects are typically excluded from depression treatment trials , leaving a gap in underst and ing the treatment outcomes . In the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) study , 2876 adult out patients diagnosed with nonpsychotic MDD were prospect ively treated with the selective serotonin-reuptake inhibitor ( SSRI ) , citalopram , and returned for at least one post-baseline visit .  Participants with SUD ( 29 % ) and without SUD ( 71 % ) were compared in regard to baseline clinical and sociodemographic features and treatment response . The group with MDD and SUD was further subdivided into those with alcohol only , drug only , and both alcohol and drug use . Despite clear sociodemographic and clinical differences , there were no significant differences between groups in the time to achieve response or rates of response to citalopram ;  however , those who endorsed both alcohol and drug use had significantly reduced rates of remission and significantly increased times to reach remission compared to the MDD group without SUD . In addition , subjects with MDD and SUD had higher risk of psychiatric serious adverse events ( 3.3 % vs. 1.5 % ) and hospitalization ( 2.8 % vs. 1.2 % ) . The results indicate that first-line treatment with citalopram in depressed patients with alcohol or drug use respond as well as those without SUD . More intensive treatment is most likely needed for MDD patients with both drug and alcohol use disorders OBJECTIVE Comparing the antidepressant effects of Citalopram with Fluoxetine and their effect on glycemic control in diabetic patients . METHODS Forty patients attending the Diabetes Research Center in Kermanshah University of Medical Sciences , Kermanshah , Iran from September 2006 to October 2007 with type II diabetes and suffering from major depression were r and omly assigned to 2 groups ( n=20 per group ) in a r and omized controlled trial method . They received up to 40 mg/d of Fluoxetine or Citalopram . Twelve weeks after treatment , patients were reassessed in terms of severity of depression and diabetic status . The Beck Depression Inventory ( BDI ) and psychiatric interview  were used to measure the severity of depression and follow up the patients . Glycosylated hemoglobin ( HbA1c ) levels and fasting blood sugar ( FBS ) was obtained to monitor glycemic control . RESULTS After the 12-week treatment , both groups showed significant improvement in severity of depression , FBS , and HbA1c . There were no significant differences between the 2 groups in terms of improvement in depression and diabetic status . CONCLUSION Fluoxetine and Citalopram can effectively reduce the severity of depression in diabetic patients without an adverse effect on glycemic control Major depression ( MD ) is underdiagnosed and undertreated in patients with temporal lobe epilepsy ( TLE ) . Side effects of some antidepressants , like increased risk of seizures and drug-drug interactions with anticonvulsants , contribute to undertreatment of MD in patients with TLE . We analyzed post hoc the data from 2 years of treatment of in patients with MD and TLE . Seventy-five patients received st and ard treatment with citalopram , mirtazapine , or reboxetine , respectively , at recommended dosage . Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20 - 30 weeks . Plasma levels of anticonvulsants were examined at admission and discharge . Seizures were documented . The antidepressive treatment was efficacious in all antidepressant groups . No case of serious adverse event or drug interaction occurred . There was no increase in frequency or severity of seizures . At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram . Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4 The present r and omized , double blind , parallel group , controlled , multi-centric trial was design ed to evaluate the efficacy and tolerability of escitalopram in comparison with citalopram and sertraline in the treatment of major depressive disorder . Out patients ( N=214 ) with an ongoing/newly diagnosed ICD-10 major depressive episode and a Hamilton Rating Scale for Depression ( HAM-D ) score of > 18 were r and omly assigned to citalopram , 20–40 mg/day ( 74 patients ) , escitalopram , 10–20 mg/day ( 69 patients ) and sertraline , 50 - 150 mg/day ( 71 patients ) , for a 4-week double-blind treatment period , with dosage adjustment ( after 2 weeks of treatment ) according to the response to treatment . Clinical response was evaluated by the 17 items HAM-D and the Clinical Global Impression ( CGI ) scales , which were recorded at baseline and at weekly intervals . Tolerability was evaluated by observed/spontaneously reported adverse changes in laboratory parameters ( baseline and after 4 weeks ) . Response rate was defined as a decrease in HAM-D score by 50 % from baseline and remission rate was defined as a HAM-D score of < 8 . Response rate at the end of two week were 58 % for escitalopram ( 10mg/day ) , 49 % for citalopram ( 20mg/day ) and 52 % for sertraline ( 50 - 100mg/day ) . Response rate at the end of four week were 90 % for escitalopram ( 10 - 20mg/day ) , 86 % for citalopram ( 20 - 40mg/day ) and 97 % for sertraline ( 100 - 150mg/day ) . The Remission rates at the end of four weeks were 74 % for escitalopram , 65 % for citalopram and 77 % for sertraline . Adverse experiences were reported by 45 % of patients in escitalopram group , 58 % patients in citalopram and 56 % patients in the sertraline group . Additionally , there were lesser dropouts and lesser requirement for dose escalation in escitalopram than in citalopram and sertraline group . In conclusion Escitalopram , the Senantiomer of the citalopram is a safe and effective antidepressant in the Indian population . It has potentially superior efficacy than citalopram and a comparable efficacy to sertraline with fewer side effects  than both citalopram and sertraline Abstract Objective : To investigate if treatment outcome for severely depressed patients depends on their baseline level of anxiety . Research design and methods : Patients with a primary diagnosis of severe major depressive disorder ( n = 459 ) were r and omised to 24 weeks of double-blind treatment with escitalopram ( 20 mg ) or paroxetine ( 40 mg ) . Post hoc analyses of efficacy in patients with a baseline HAM-A total score ≤20 ( n = 171 ) or > 20 ( n = 280 ) were based on analysis of covariance ( ANCOVA ) ( ITT , LOCF ) . Results : At week 24 , the mean change from baseline in MADRS total scores was −24.2 for escitalopram-treated patients ( n = 141 ) and −21.5 for paroxetine-treated patients ( n = 139 ) ( p < 0.05 ) in high baseline anxiety patients and the mean change from baseline in HAM-A total score was −17.4 ( escitalopram ) and −15.1 ( paroxetine ) ( p < 0.05 ) . When examining the proportion of complete remitters ( CGI-S = 1 ) after 24 weeks of treatment , there was an increasing treatment difference as a function of baseline HAM-A total score in favour of escitalopram ( ITT , LOCF ) . There was no treatment difference in the low baseline anxiety group . Significantly more patients ( p < 0.01 ) withdrew from the paroxetine group ( 31 % ) than from the escitalopram group ( 17 % ) , partly as the result of significantly more withdrawals due to AEs ( p < 0.05 ) . Incidence of AEs and withdrawals were not related to baseline anxiety and there were no significant differences in the incidence of individual AEs  with escitalopram compared to paroxetine . Limitations : The post hoc nature of these analyses , the absence of placebo control group , and the requirement that patients should be suffering from severe depression , limit the generalisability of the results . Conclusion : Patients with severe depression together with comorbid anxiety symptoms responded significantly better to treatment with escitalopram 20 mg compared with paroxetine 40 mg . Contrary to paroxetine , escitalopram maintained its efficacy with increasing baseline anxiety levels CONTEXT Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women . OBJECTIVE To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors ( SRIs ) in women . DESIGN , SETTING , AND PARTICIPANTS An 8-week prospect i ve , parallel-group , r and omized , double-blind , placebo-controlled clinical trial conducted between September 1 , 2003 , and January 1 , 2007 , at 7 US research centers that included 98 previously sexually functioning , premenopausal women ( mean [ SD ] age 37.1 [ 6 ] years ) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction . INTERVENTION Forty-nine patients were r and omly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity . MAIN OUTCOME MEASURES The primary outcome measure was the mean difference in change from baseline to study end ( ie , lower ordinal score ) on the Clinical Global Impression sexual function scale . Secondary measures included the Female Sexual Function Question naire , the Arizona Sexual Experience scale-female version , the University of New Mexico Sexual Function Inventory-female version , a sexual activity event log , and the Hamilton Depression Rating scale . Hormone levels were also assessed . RESULTS In an intention-to-treat analysis , women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 ( 95 % confidence interval [ CI ] , 1.6 - 2.3 ) compared with those taking placebo ( 1.1 ; 95 % CI , 0.8 - 1.5 ) , with a mean end point difference of 0.8 ( 95 % CI , 0.6 - 1.0 ; P = .001 ) . Assigning baseline values carried forward to the 22 % of patients who prematurely discontinued result ed in a mean end point in the sexual function score of 1.5 ( 95 % CI , 1.1 - 1.9 ) among women taking sildenafil compared with 0.9 ( 95 % CI , 0.6 - 1.3 ) among women taking placebo with a mean end point difference of 0.6 ( 95 % CI , 0.3 - 0.8 ; P = .03 ) . Baseline endocrine levels were within normal limits and did not differ between groups . The mean ( SD ) Hamilton scores for depression remained consistent with remission in both groups ( 4.0 [ 3.6 ] ; P = .90 ) . Headache , flushing , and dyspepsia were reported frequently during treatment , but no patients withdrew because of serious adverse effects . CONCLUSION In this study population , sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00375297 The aim of this study was to determine predictors of the response to escitalopram , a selective serotonin re-uptake inhibitor antidepressant and memantine , a non-competitive glutamate NMDA receptor blocker , for the treatment of major depression comorbid with alcohol dependence . Eighty alcohol dependent treatment-seeking adult patients with comorbid major depressive disorder were r and omized to receive either memantine 20 mg or escitalopram 20 mg for 26 weeks . In both treatment groups , depression was reduced significantly . Comparisons were made between patients in remission ( final Montgomery-Asberg Depression Rating Scale (MADRS)<or=12 ) and non-responding patients ( MADRS decrease<50 % ) . The age at onset of the first major depressive episode significantly correlated with the treatment response in the escitalopram group ; the mean age at onset of depression among patients on the non-responders group was 13.7+/-4.0 years and 31.9+/-11.9 years in remission . These results are significantly different from those with memantine . Our study provides evidence that the onset of the first major depressive episode might be a clinical ly relevant predictor of a response to escitalopram treatment in patients with major depression and comorbid alcohol dependence This multicentre , double-blind , r and omised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor ( SNRI ) antidepressant milnacipran ( 50 mg twice daily , n=53 ) with the established tricyclic agent imipramine ( 75 mg twice daily , n=56 ) over a period of 6 weeks , in patients with major depression ( Montgomery-Asberg depression rating score ( MADRS ) > or = 25 ) . Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation , after a 3- to 7-day washout period . Concomitant psychiatric medication was limited to lorazepam , cyamemazine , chloral hydrate and long-term uncomplicated lithium therapy . Assessment for efficacy using the MADRS and Hamilton rating scales of depression , a visual analogue scale and global evaluation revealed both agents to be highly effective ( P=0.0001 ) in this group of patients . Milnacipran was found to be of similar efficacy to imipramine .  Tolerance , assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events , revealed a clear advantage for milnacipran . The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine . Furthermore , the patient drop-out rate with imipramine was double that experienced with milnacipran . Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance . Therefore , milnacipran constitutes an important new treatment option in major depression BACKGROUND The study objective was to evaluate variations in genes implicated in antidepressant mechanism of action for association with response to duloxetine treatment in major depressive disorder ( MDD ) . METHODS We assessed response over 6 weeks in 250 duloxetine-treated Caucasian patients in a r and omized , double-blind study of patients with MDD . Single nucleotide polymorphisms ( SNPs ) were genotyped in 19 c and i date genes selected based on evidence for involvement in antidepressant mechanism of action . Primary analysis examined baseline to end point reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score , using a set-based test for association for each gene . Follow-up analyses examined individual SNPs within any significant gene for association with reduction in HAMD17 and 30-item Inventory of Depressive Symptomatology-Clinician Rated ( IDS-C-30 ) . RESULTS After correction for multiple comparisons , only COMT was associated with change in HAMD17 ( experiment wide p = .018 ) . Peak association was detected with rs165599 ( p = .006 ) , which accounted for approximately 3 % of variance in HAMD17 change and > 4 % of variance in IDS-C-30 change ( p = .001 ) . The least-squared mean change ( SE ) in HAMD17 score by rs165599 genotype was -10.8 ( 1.2 ) , -8.7 ( .6 ) , and -6.5 ( .7 ) for patients with GG , GA , and AA genotypes , respectively . For SNPs in serotonin 2A receptor ( HTR2A ) previously associated with citalopram response , including rs7997012 , no significant evidence of association with duloxetine response was identified . CONCLUSIONS Single nucleotide polymorphisms in COMT were associated with symptom change in duloxetine-treated patients with MDD . If replicated , the magnitude of the COMT genotype effect is of clinical relevance OBJECTIVE Chronic fatigue syndrome ( CFS ) is a debilitating disorder with prominent symptoms of malaise , fatigue , myalgia , arthralgia , and impaired concentration . The symptoms of CFS may often overlap those of Major Depressive Disorder ( MDD ) . Treatment of CFS has generally been disappointing . We hypothesized that s-citalopram therapy may improve the symptoms of both disorders in CFS patients with co-morbid depression . METHODS 16 patients received s-citalopram 10 mg to 20 mg daily for up to 12 weeks . Outcome measures of CFS included the Chalder Fatigue Question naire ( CFQ ) , the multi-dimensional Fatigue Impact Scale ( FIS ) , the CFS symptom rating ( CFS-SR ) 100 mm visual analogue scale , and the clinical global impressions severity ( CGI/S ) and change ( CGI/C ) ratings . Secondary outcomes of MDD included the Hamilton Depression Rating ( HAM-D ) , Beck Depression Inventory ( BDI ) , and the CGI/S and CGI/C ratings of MDD . RESULTS We observed reductions in the mean CFQ score ( p<0.0005 ) , FIS score ( p<0.0005 ) , and CGI/S ( p<0.0005 ) and CGI/C ( p<0.0005 ) ratings over time . There was a significant improvement in 5 of the 8 CFS-SR symptoms : post-exertion malaise ( p=0.001 ) , headaches ( p<0.0005 ) , un-refreshing sleep ( p<0.0005 ) , and impaired memory and concentration ( p<0.0005 ) . There was also a reduction in mean HAM-D ( p<0.0005 ) , BDI ( p<0.0005 ) , CGI/S ( p=0.001 ) and CGI/C ( p<0.0005 ) ratings of MDD . LIMITATIONS The sample size was limited and the study design was not double-blind or placebo controlled . CONCLUSION We observed a significant reduction in both CFS and co-morbid MDD symptom severity ratings , and improvement in 5 of 8 core somatic symptoms of CFS during s-citalopram therapy OBJECTIVE The objective of this double-blind , r and omised , placebo-controlled , multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression . During the 6-week treatment phase , the course of depression was documented by use of HAMD ( items 1 - 17 ) , the von Zerssen 's Adjective Mood Scale ( BfS ) and the CGI scales . The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI ( 900 mg ) to the SSRI citalopram ( 20 mg ) and superiority of hypericum over placebo . METHODS Out patients ( N = 388 ) suffering from moderate depression were enrolled . The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI , the occurrence of adverse events and the investigation of laboratory parameters and vital signs . RESULTS From almost identical baseline values of 21.9 + /- 1.2 points ( hypericum extract ) , 21.8 + /- 1.2 points ( citalopram ) and 22.0 + /- 1.2 points ( placebo ) , the HAMD score was reduced to 10.3 + /- 6.4 ( hypericum extract ) , 10.3 + /- 6.4 ( citalopram ) and 13.0 + /- 6.9 ( placebo ) , respectively . Based on this data , the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram ( p < 0.0001 ) and the superiority of this hypericum extract over placebo ( p < 0.0001 ) was demonstrated . At the end of treatment 54.2 % ( hypericum extract ) , 55.9 % ( citalopram ) and 39.2 % ( placebo ) of the patients were assessed as therapy responders . The secondary efficacy parameters , change in BfS , CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group , and significantly superior to the placebo group . Significantly more adverse events with " certain " , " probable " or " possible " relation to study medication were documented in the citalopram group ( hypericum : 17.2 % , citalopram : 53.2 % , placebo : 30 % ) . In most cases , the investigators assessed the tolerability of hypericum extract , citalopram and placebo as " good " or " very good " . CONCLUSION The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated , as well as a better safety and tolerability of hypericum extract in comparison to citalopram . These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of out patients with moderate depression Drug-induced improvement of depression may be mediated by changes in sleep physiology . The aim of this study was to relate changes in sleep polygraphic variables to clinical state during treatment with citalopram , a highly specific serotonin uptake inhibitor . Sixteen patients took part . The study was single-blind and uncontrolled . A 1-week wash-out period was followed by 1 week of placebo administration , a medication period of 5 weeks , and a 1-week placebo period . For the entire group a significant decrease of rapid eye movement sleep ( REMS ) and a significant lengthening of REMS latency were observed initially as well as at the end of treatment . No changes in sleep continuity were found , but non-REMS stage 2 ( percentage ) was significantly increased . On the basis of clinical change , as expressed by the scores of the Hamilton Rating Scale for Depression , at the end of the citalopram treatment the patient group was split in two halves : eight less and eight more improved patients . The groups did not differ with respect to any sleep polygraphic varible Background Depression is a leading cause of disability worldwide and depressive symptoms are common in later life . Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine ( tHcy ) , but the results of r and omized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6 , B12 and folate benefits depressive symptoms . We design ed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6 , B12 and folate increases the efficacy of st and ard antidepressant treatment . Methods / Design The B-VITAGE trial is a 12-month r and omized , double-blind , placebo-controlled trial of daily citalopram ( 20 to 40 mg ) plus B12(0.4 mg ) , B6 ( 25 mg ) and folic acid ( 2 mg ) or citalopram ( 20 to 40 mg ) plus placebo for the treatment of depression in later life . The trial aims to recruit over 300 older adults with major depression ( DSM-IV ) and has been powered to detect the impact of an intervention associated with moderate effect size . Depressive symptoms will be rated with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The trial has two main outcomes of interest : a reduction of 50 % or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12 , 26 and 52 according to DSM-IV criteria . We hypothesize that subjects r and omly allocated to the vitamin arm of the study will be more likely to show a clinical ly significant improvement and achieve and maintain remission of symptoms at 12 , 26 and 52 weeks . Secondary outcomes of interest include compliance with treatment , reduction in the severity of depressive symptoms , switching to different antidepressants , the use of non-pharmacological antidepressant treatments , response to treatment according to MTHFRC677 T genotype , and changes in cognitive function over 52 weeks . Conclusions The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to st and ard antidepressant treatment . We anticipate that our findings will have implication s for clinical practice and health policy development . Trial Registration The trial is registered with the Australian Clinical Trials Registry , trial number ( ())ACTRN12609000256279 Background In some r and omized trials successful laparoscopic cholecystectomy for cholecystitis is associated with an earlier recovery and shorter hospital stay when compared with open cholecystectomy . Other studies did not confirm these results and showed that the potential advantages of laparoscopic cholecystectomy for cholecystitis can be offset by a high conversion rate to open surgery . Moreover in these studies a similar postoperative programme to optimize recovery comparing laparoscopic and open approaches was not st and ardized . These studies also do not report all eligible patients and are not double blinded . Design The present study project is a prospect i ve , r and omized investigation . The study will be performed in the Department of General , Emergency and Transplant Surgery St Orsola-Malpighi University Hospital ( Bologna , Italy ) , a large teaching institutions , with the participation of all surgeons who accept to be involved in ( and together with other selected centers ) . The patients will be divided in two groups : in the first group the patient will be su bmi tted to laparoscopic cholecystectomy within 72 hours after the diagnosis while in the second group will be su bmi tted to laparotomic cholecystectomy within 72 hours after the diagnosis . Trial Registration TRIAL REGISTRATION NUMBER IS RCT N27929536 – The ACTIVE ( Acute Cholecystitis Trial Invasive Versus Endoscopic ) study . A multicentre r and omised , double-blind , controlled trial of laparoscopic versus open surgery for acute cholecystitis in adults BACKGROUND clinicians have long noticed a correlation between physiological markers of inflammation and depression . The best-known example is the activation of the hypothalamus-pituitary-adrenal axis and cortisol secretion ; however more recent studies have demonstrated increased salivary prostagl and ins and plasma acute phase proteins in depressed patients . To date four r and omised controlled trials have used celecoxib or rofecoxib as adjuncts to serotonin selective reuptake inhibitors in the treatment of depression . These suggested a statistically significant decrease in depressive symptoms in the patients taking NSAIDs and SSRIs , compared to patients taking SSRIs alone . Interpretation of these results is limited by the small sample size and short duration of these preliminary studies . The research only considers depressed patients receiving treatment in secondary care ; no study has examined the effectiveness of NSAIDs as an adjunct in primary care , even though most cases of depression in the UK are managed in the community by general practitioners . PROPOSAL we propose a multi-centre double-blinded r and omised controlled trial with two objectives : to determine whether citalopram plus celecoxib dual therapy achieves a greater reduction in depressive symptoms ( quantified using the Hamilton Depression Rating Scale ( HDRS ) ) within four weeks , compared to citalopram monotherapy ; and to determine whether citalopram plus celecoxib dual therapy is more likely to achieve remission ( HDRS score ? 7 ) of moderate to severe depression within six months , compared with citalopram monotherapy . The endpoints will be the reduction in HDRS score after 4 weeks of treatment , and the HDRS score after 26 weeks of treatment . The study will enrol 452 participants from general practice s who have a moderate or severe , current or recurrent major depressive episode when medication with an SSRI is considered . The study population will be stratified according to age , sex , HDRS score , age of onset of first episode , number of previous depressive episodes and duration of current episode . The population will then be r and omised into two groups . Subjects will be interviewed to determine HDRS score , measure blood pressure , count pills and discuss side-effects . This will occur weekly for the first four weeks , and every four weeks thereafter Introduction Erythropoietin ( Epo ) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression . We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers . Objective The current study aim ed to explore the effects of Epo on the neural processing of emotional information in depressed patients . Material s and methods Seventeen patients with acute major depressive disorder were r and omised to receive Epo ( 40,000 IU ) or saline iv in a double-blind , parallel-group design . On day 3 , we assessed neural responses to positive , negative and neutral pictures during fMRI followed by picture recall after the scan . Mood and blood parameters were assessed at baseline and on day 3 . Results Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus , ventromedial prefrontal and parietal cortex . After the scan , Epo-treated patients showed improved memory compared with those that were given placebo . The effects occurred in the absence of changes in mood or haematological parameters , suggesting that they originated from direct neurobiological actions of Epo . Conclusions These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression . The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism CONTEXT Mindfulness-based cognitive therapy ( MBCT ) is a group-based psychosocial intervention design ed to enhance self-management of prodromal symptoms associated with depressive relapse . OBJECTIVE To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy  , the current st and ard of care . DESIGN Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were r and omized to receive maintenance antidepressant medication , MBCT , or placebo and were followed up for 18 months . SETTING Outpatient clinics at the Centre for Addiction and Mental Health , Toronto , Ontario , Canada , and St Joseph 's Healthcare , Hamilton , Ontario . PARTICIPANTS One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes . Of these , 84 achieved remission ( 52.5 % ) and were assigned to 1 of the 3 study conditions . INTERVENTIONS Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT , continued taking their therapeutic dose of antidepressant medication , or discontinued active medication and were switched to placebo . MAIN OUTCOME MEASURE Relapse was defined as a return , for at least 2 weeks , of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV . RESULTS Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in r and omized patients ( P = .03 ) . Among unstable remitters ( 1 or more Hamilton Rating Scale for Depression score > 7 during remission ) , patients in both MBCT and maintenance treatment showed a 73 % decrease in hazard compared with placebo ( P = .03 ) , whereas for stable remitters ( all Hamilton Rating Scale for Depression scores ≤7 during remission ) there were no group differences in survival . CONCLUSIONS For depressed patients achieving stable or unstable clinical remission , MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy . Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters Patients with major depressive disorder ( MDD ) usually suffer from altered cognitive functions of episodic memory , working memory , mental processing speed and motor response . Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD . The aim of this work is to study the effects of serotonergic reuptake inhibitors ( SSRIs ) and serotonergic-noradrenergic reuptake inhibitors ( SNRIs ) treatments to improve the performance on memory tasks and mental processing speed in MDD . Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery . The subjects were medicated with escitalopram ( n=36 ) or duloxetine ( n=37 ) for 24 weeks . At the end of the trial , the subjects were assessed again with the same neuropsychological battery used prior to the treatment . Both treatments improved importantly the episodic memory and to a lesser extent , working memory , mental processing speed and motor performance . Our results suggest that cognition is partially independent from improvement in clinical symptoms . Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment , but SNRI was superior to SSRI  at improving episodic and working memory . Our work indicates that the superiority of SNRI over the SSRI  at episodic memory improvement is clinical ly relevant Several previous studies , including a meta- analysis , reported no significant differences between various selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder . However , because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups , a head-to-head comparative study between SSRIs in different population s may be enlightening . We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded r and omized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder . Fifty-one patients were r and omly assigned to citalopram or sertraline treatment . The Montgomery-Åsberg Depression Rating Scale ( MADRS ) was used as the primary outcome . Efficacy and adverse effects were analyzed in an intent-to-treat population . Efficacy was analyzed using a last-observation-carried-forward method for early terminators . There were no significant differences in demographic characteristics at baseline . No significant differences were found in MADRS scores between citalopram and sertraline at baseline ( 36.6 ± 5.5 vs 38.2 ± 4.9 ; P = 0.322 ) or at the end of treatment ( week 6 ; 10.8 ± 10.0 vs 16.7 ± 11.3 ; P = 0.082 ) . However , MADRS scores in the citalopram group were significantly lower at week 1 ( 25.2 ± 8.5 vs 30.4 ± 6.1 ; P = 0.029 ) and week 3 ( 15.9 ± 10.0 vs 22.1 ± 8.7 ; P = 0.037 ) . Overall , treatment-emergent adverse effects were reported by 14.3 % and 28.6 % of patients in the citalopram and sertraline groups , respectively . In conclusion ,  citalopram  and sertraline were both efficacious and well tolerated . However , citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment , although the statistic was not significant Pre- clinical studies , active-control clinical trials and meta-analyses indicate that escitalopram ( S-citalopram ) might be more effective than citalopram , the racemic mixture of S- and R-citalopram . The present study aim ed to confirm the superior efficacy of escitalopram over citalopram . A double-blind , r and omized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram ( 20 mg/day ) with citalopram ( 40 mg/day ) over 8 weeks in out patients with major depressive disorder ( MDD ) [ baseline Montgomery – Asberg Depression Rating Scale ( MADRS ) score ≥30 ] . Primary efficacy parameter was change from baseline to last assessment in the MADRS total score . Out of 138 ( aged 44.1±10.9 years ; initial MADRS score 36.3±4.8 ) and 142 ( aged 46.2±11.1 years ; initial MADRS score 35.7±4.4 ) evaluable patients who were r and omized to escitalopram and citalopram  , respectively , six and 15 withdrew prematurely  ( P=0.05 ) . The MADRS score decreased more in the escitalopram than in the citalopram arm ( –22.4±12.9 versus –20.3±12.7 ; P<0.05 ) . There were more treatment responders with escitalopram ( 76.1 % ) than with citalopram ( 61.3 % , P<0.01 ) . Adjusted remitter rates were 56.1 % and 43.6 % , respectively ( P<0.05 ) . Tolerability was similar in both groups . This r and omized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD Orthostatic hypotension , the clinical ly most important side effect in treatment with tricyclic antidepressants , was investigated in a double-blind study with clomipramine and the selective serotonin reuptake inhibitor citalopram given for 5 weeks . All patients were initially given placebo for 1 week . In the clomipramine group ( n=17 ) a significant orthostatic drop in the systolic blood pressure was observed during treatment ; this remained significant over the whole investigational period . A curvilinear correlation was demonstrated between the orthostatic drop in systolic blood pressure and the plasma levels of clomipramine and desmethylclomipramine . The most pronounced orthostatic reaction was thus seen in 1–2 weeks , at plasma levels of 25–75 μg/l ( clomipramine ) . The correlation between the subjective symptoms and the measured orthostatic drop was poor , as was the correlation between the subjective symptoms and the plasma levels of the two active compounds . The change in orthostatic heart rate during clomipramine treatment was insignificant . In the citalopram  group ( n=15 ) no significant changes in orthostatic blood pressure or heart rate were demonstrated during treatment and these patients had no orthostatic complaints OBJECTIVE This study examines whether continuation therapy with citalopram can prevent a relapse following remission of major depression due to traumatic brain injury . METHOD After 65 subjects with DSM-IV-diagnosed major depression following traumatic brain injury were treated with open-label citalopram ( 20 mg to 50 mg/d ) , 25 subjects ( 38.5 % ) met criteria for remission . Of those , 21 ( 84.0 % ) were r and omly assigned to either same-dose citalopram or placebo and followed monthly over 40 weeks . Remission was defined as a Hamilton Depression Rating Scale ( HDRS ) score of ≤ 7 or a Clinical Global Impressions-Improvement rating of " much improved " or better . The main outcome variable was the presence of relapse , as defined by meeting criteria for major depressive episode according to the DSM-IV and an HDRS score ≥ 16 . Data were collected from February 16 , 2005 , to May 5 , 2008 . RESULTS Ten subjects were r and omly assigned to citalopram and 11 to placebo . There were 3 dropouts , including 1 for adverse drug effects ( diarrhea ) . Relapse occurred in 11 subjects ( 52.4 % ) , with a mean ± SD time to relapse of 23.52 ± 16.6 weeks . The groups did not differ in relapse rates ( drug : 50.0 % [ 5/10 ] vs placebo : 54.5 % [ 6/11 ] , Fisher exact test , P = .835 ) or time to relapse ( log rank test χ² = 0.148 , P = .700 ) . CONCLUSIONS The present study suggests important limitations of continuation pharmacotherapy in the prevention of relapse of major depression following traumatic brain injury . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00162916 BACKGROUND It is well established that depressive disorders are more prevalent in women ; however gender differences in the pharmacological response to antidepressants are not a consistent finding in all reports . It is considered that this discrepancy can be explained by the fact that in most clinical trials drug use for comparative purpose s is not completely different . In this study gender differences in antidepressant response with citalopram ( CTP ) , a selective serotonin reuptake inhibitor and reboxetine ( RBX ) , a selective noradrenaline reuptake inhibitor were evaluated in a group of young men and premenopausal women . METHOD Eighty-six depressed patients 18 to 40 years old participated in an 8-week double-blind clinical trial . Subjects were divided in four groups according to sex and treatment assignation : females treated with CTP ( n = 25 ) or RBX ( n = 23 ) , and males treated with CTP ( n = 19 ) or RBX ( n = 19 ) . Response was determined using HDRS and BDI . RESULTS ANOVA analysis considering change in HDRS scores from baseline to last evaluation found a significant interaction between gender and type of treatment . Females treated with CTP showed a significantly greater response than females treated with RBX , while in men no differences were observed for both drugs . LIMITATIONS Replication using larger sample size and longer treatment periods is required . CONCLUSIONS These results support previous findings which show that premenopausal women respond better than men to serotonergic antidepressants . They also support that a plausible interaction between gonadal hormones and serotonin may explain gender differences in antidepressant response OBJECTIVE Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied . The extent and implication s of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated , to the authors ' knowledge . METHOD The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry , the Archives of General Psychiatry , the Journal of Clinical Psychopharmacology , and the Journal of Clinical Psychiatry between 2001 and 2003 . RESULTS Among 397 clinical trials identified , 239 ( 60 % ) reported receiving funding from a pharmaceutical company or other interested party , and 187 studies ( 47 % ) included at least one author with a reported financial conflict of interest . Among the 162 r and omized , double-blind , placebo-controlled studies examined , those that reported conflict of interest were 4.9 times more likely to report positive results ; this association was significant only among the subset of pharmaceutical industry-funded studies . CONCLUSIONS Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo OBJECTIVE The present study aim ed to 1 ) assess facial expression recognition in subjects with a previous history of major depressive disorder relative to subjects with no history of depression and 2 ) characterize the effects of acute citalopram infusion on recognition performance for both groups . METHOD Unmedicated euthymic women with a history of major depression and matched comparison subjects with no history of depression were given a facial expression  recognition task following intravenous infusion of saline or citalopram ( 10 mg ) in a double-blind , between-group design . RESULTS Following saline infusion , subjects with a previous history of depression showed a selectively greater recognition of fear relative to the subjects with no history of depression . The abnormal fear processing observed in the subjects with a previous history of depression was normalized following citalopram infusion , an effect that was opposite to that seen with the subjects with no history of depression . CONCLUSIONS These results suggest that increased recognition of fear is a trait vulnerability marker for depression and that this is normalized following a single dose of citalopram OBJECTIVE Few controlled studies have addressed the issue of which antidepressant medications should be recommended for out patients who have not responded to multiple treatment trials . This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant ( nortriptyline ) following two prospect i ve , consecutive , unsuccessful medication treatments for nonpsychotic major depressive disorder . METHOD Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks ( first step ) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone ( second step ) , adult out patients ( N=235 ) with nonpsychotic major depressive disorder were r and omly assigned to 14 weeks of treatment with mirtazapine ( up to 60 mg/day ) ( N=114 ) or nortriptyline ( up to 200 mg/day ) ( N=121 ) . The primary outcome , symptom remission , was defined a priori as a total exit score of < /=7 on the 17-item Hamilton Rating Scale for Depression . The 16-item Quick Inventory of Depressive Symptomatology-Self-Report ( QIDS-SR(16 ) ) , obtained at treatment visits , provided secondary outcomes of remission ( score < /=5 at exit ) and response ( > /=50 % reduction in score from baseline ) . RESULTS For mirtazapine , remission rates were 12.3 % and 8.0 % per the Hamilton and QIDS-SR(16 ) scores , respectively . For nortriptyline , remission rates were 19.8 % and 12.4 % , respectively . QIDS-SR(16 ) response rates were 13.4 % for mirtazapine and 16.5 % for nortriptyline . Neither response nor remission rates statistically differed by treatment , nor did these two treatments differ in tolerability or adverse events . CONCLUSIONS Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials result ed in low remission rates ( < 20 % ) among patients with major depressive disorder Two dose levels of citalopram , 10–30 mg and 20–60 mg , were compared with imipramine , 50–150 mg , in depressed patients treated in general practice . This was a multicentre study carried out in Denmark , Sweden , Norway , and Finl and . The duration of treatment was 6 weeks with an optional continuation phase of a further 16 weeks . The patients were assessed by means of the Hamilton Rating Scale for Depression ( HAMD ) , Clinical Global Impressions ( CGI ) , and a visual analogue self-rating scale for depression . Observed and spontaneously reported adverse events were recorded . A total of 472 patients were entered into the study and 400 patients completed the 6 week trial period . A total of 297 patients completed the optional 22 week double-blind period . A clear reduction of the HAMD total scores was seen in all three treatment groups with no significant differences between groups . A reduction of the HAMD anxiety factor and sleep factor scores was also seen with no significant differences between treatments . The imipramine-treated patients showed a higher frequency of adverse events , especially the anti-cholinergic type , than citalopram-treated patients . Most patients entered into the continuation phase remained well Sleep disturbance is common in major depressive disorder ( MDD ) , and is often characterized by early-morning waking . Melatonin is a hypnotic and synchronizes circadian rhythms . It may also be an antidepressant . The melatonin agonists , ramelteon and agomelatine , have hypnotic and antidepressant properties , but there is a dearth of trials investigating the use of melatonin in MDD . This r and omized , controlled trial aim ed to determine whether exogenous melatonin is a sleep promoter and antidepressant . Thirty-three participants with a Diagnostic and Statistical Manual of Mental Disorders ( fourth edition ) diagnosis of MDD and early-morning waking were selected for a 4-week , r and omized , double-blind trial of slow-release melatonin ( 6 mg ; vs. placebo ) given at bedtime over 4 weeks . Sleep was measured subjectively using  sleep diaries  and the Leeds Sleep Evaluation Question naire and objective ly using  wrist actigraphy .  Of the 33 participants , 31 completed the trial . General Linear Modelling showed significant improvements in depression and sleep over time , but this was not specific to melatonin . However , there was a trend towards an improvement in mood with melatonin , and no adverse side effects were observed . In conclusion , melatonin may be beneficial for treating MDD , it seems to be safe and well tolerated , but its potential for treating  depression in people who do not wish to take antidepressants requires further evaluation Neuroendocrine challenge tests in depressed patients have revealed a blunted hormonal reaction to serotonergic stimuli . In the present study , citalopram was chosen as the serotonergic agent for neuroendocrine stimulation . Compared to earlier challenge agents , citalopram has the advantage of serotonergic selectivity , its application is well tolerated and the possibility of intravenous application reduces pharmacokinetic interference . Sixteen patients suffering from an acute episode of major depression and 16 healthy controls underwent the stimulation procedure with 20 mg of citalopram and placebo . Whereas significant differences in the secretion of prolactin and cortisol between citalopram and placebo challenge were observed in the control group , no differences were found in the group of depressed patients . Comparison of depressed patients and controls showed a significantly blunted prolactin secretion in patients . Differences in cortisol secretion following serotonergic stimulation with citalopram did not become significant . The stimulation procedure was well tolerated in all subjects , although a higher number of side effects was observed in the control group . The amount of side effects did not correlate with the hormone responses . These results are in line with the hypothesis of serotonergic hypofunction in depressed patients . In conclusion , the 20-mg citalopram challenge test is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness OBJECTIVES The authors previously reported that repetitive transcranial magnetic stimulation ( rTMS ) produced a response rate of 39.4 % among 62 patients with treatment resistant vascular depression . This study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS . DESIGN Patients were r and omly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods . After rTMS , all patients were given 20 mg/day of citalopram for 9 weeks and reevaluated at 3 , 6 , and 9 weeks . SETTING Outpatient continuation treatment trial . PARTICIPANTS Patients with vascular depression ( N = 62 ) , as determined by magnetic resonance imaging hyperintensities and three or more clinical risk factors for vascular disease without other major medical illness , were recruited . They had onset of major depression after age 50 and failed at least one trial of antidepressants . INTERVENTION After rTMS or sham treatment , all treatment responders were given citalopram for 9 weeks . RESULTS Among the 33 patients who were given rTMS , 13 responded ( i.e. , > 50 % decline in Hamilton Depression Scale score ) . Of these 13 , all completed the 9 weeks of continuation treatment . There were nine patients who continued to be responders and four who had a relapse of depression . CONCLUSION More effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders Noninvasive electrophysiological neuroimaging applied to cognitive components of event-related potentials ( ERPs ) may differentiate between structural and energetic processes related to information processing . The structural level , revealed by the location of the local maxima of the current source density distribution , describes the time-dependent network of activated brain areas . The magnitude of the source strength , a measure of the energetic component , describes the allocation of processing re sources . ERPs were recorded in an odd-ball paradigm and low-resolution brain electromagnetic tomography ( LORETA ) was applied for st and ard and target ERP components . In a group of 60 menopausal depressed patients of 45 - 60 years of age , reduced P300 source strength was observed bilaterally , temporally and medially prefrontally reaching to rostal parts of the anterior cingulate , compared with 29 age-matched controls . In a double-blind , placebo-controlled study , 2 mg of the antidepressant citalopram induced a significant increase of P300 source strength in the ( left ) prefrontal cortex and precuneus compared with placebo , reaching to the posterior cingulate . Similar increases were observed after 800 mg S-adenosyl-L-methionine ( SAMe ) administered intravenously in ten young healthy subjects aged 22 - 33 , and they were even more pronounced in ten elderly healthy subjects aged 56 - 71 . Thus , ERP-tomography identified changes in energetic sources in brain areas predominantly involved in depression and in antidepressant action Objective : To examine the efficacy and tolerability of escitalopram ( ESCIT ) compared to estrogen and progestogen therapy ( EPT ) for the treatment of symptomatic peri- and postmenopausal women . Design : Forty women ( aged 40 - 60 years ) with depressive disorders and menopause-related symptoms were r and omly assigned to an 8-week open trial with ESCIT ( flexible dose , 10 - 20 mg/day ; fixed dose , 10 mg/day for the first 4 weeks ) or estrogen plus progestogen therapy ( ethinyl estradiol 5 & mgr;g/day plus norethindrone acetate 1 mg/day ) . Primary outcome measures included Montgomery-Asberg Depression Rating Scale and the Greene Climacteric Scale at week 8 . Secondary outcome measures included the Clinical Global Impressions as well as sleep and quality of life assessment s. Results : Thirty-two women ( 16 on EPT , 16 on ESCIT ) were included in the analyses . Full remission of depression ( score of < 10 on the Montgomery-Asberg Depression Rating Scale ) was observed in 75 % ( 12/16 ) of subjects treated with ESCIT , compared to 25 % ( 4/16 ) treated with EPT ( P = 0.01 , Fisher 's exact tests ) . Remission of menopause-related symptoms ( > 50 % decrease in Greene Climacteric Scale scores ) was noted in 56 % ( 9/16 ) of women treated with ESCIT compared to 31.2 % ( 5/16 ) on EPT ( P = 0.03 , Pearson 's & khgr;2 tests ) . Improvement in sleep , hot flashes , and quality of life was observed with both treatments . Conclusions : ESCIT is more efficacious than EPT for the treatment of depression and has a positive impact on other menopause-related symptoms . ESCIT may constitute a treatment option for symptomatic menopausal women who are unable or unwilling to use hormone therapy This study is a comparison across treatment setting s of two previously published trials , namely the Danish University Antidepressant Group ( DUAG ) study on citalopram vs. clomipramine in hospitalized patients with major depression , and the Nordic citalopram vs. imipramine  study of depressed patients treated by their family doctors . The Hamilton Depression Scale ( HAM‐D ) had the same level of inter‐rater reliability and construct validity in the two setting s. Using a HAM‐D score of 7 or less as the criterion for full remission , clomipramine was superior to imipramine and citalopram . Using a reduction of the baseline HAM‐D score by 50 % or more as a response criterion , there were no differences between the three antidepressants after 5 or 6 weeks of treatment . Citalopram  showed superior tolerability to the tricyclic antidepressants OBJECTIVES This preliminary study examines the efficacy of 12-week home-delivered problem adaptation therapy ( PATH ) versus home-delivered supportive therapy ( ST ) in reducing  depression and disability in 30 depressed , cognitively impaired , disabled older adults . DESIGN A 12-week r and omized clinical trial . Research assistants were unaware of the participants ' r and omization status . Assessment s were conducted at baseline , 6 weeks , and 12 weeks . SETTING Weill-Cornell Advanced Center for Interventions and Services Research . PARTICIPANTS Thirty elders with major depression , cognitive impairment , and disability were recruited through advertisement and the Home-Delivered Meals Program of the Westchester County Department of Senior Programs and Services . INTERVENTION PATH is a home-delivered intervention design ed to reduce depression and disability in depressed , cognitively impaired , disabled elders .  PATH is based on problem-solving therapy and integrates environmental adaptation and caregiver participation . PATH is consistent with Lawton 's ecologic model of adaptive functioning in aging . MEASUREMENTS Depression and disability were measured with Hamilton Depression Rating Scale-24 items and Sheehan Disability Scale , respectively . Client Satisfaction Question naire was used to assess patient satisfaction with treatment . RESULTS Mixed-effects model analyses revealed that PATH was more efficacious than ST in reducing depression and disability at 12 weeks . Participants in both treatment groups were satisfied with treatment . CONCLUSIONS This preliminary study suggests that PATH is well accepted and efficacious in depressed elders with major depression , cognitive impairment , and disability . Because this population may not adequately respond to antidepressant medication treatment , PATH may provide relief to many patients who would otherwise remain depressed and continue to suffer BACKGROUND MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale ( HAMD(17 ) ) and the Clinical Global Impressions Scale ( CGI ) . METHOD HAMD(17 ) , MADRS , and CGI ratings from patients with major depression ( DSM-IV ) were analyzed ( N=85 ) . Receiver operating characteristics ( ROC ) curves were applied . RESULTS Mean age was 51.4+/-14.5 years , 69 % were female .  Mean MADRS scores were 23.4+/-13.2 , HAMD(17 ) , MADRS , and CGI scores were highly correlated ( r>0.85 ; P<0.0001 ) . Best separation between moderate and severe depression according to CGI criteria was achieved with a MADRS score of 31 ( sensitivity 93.5 % , specificity 83.3 % ) . LIMITATIONS Studies to vali date severity gradations including DSM-IV or ICD-10 diagnostic severity categories are recommended . CONCLUSIONS Empirically based MADRS cut-off scores to separate moderate from severe depression on the basis of HAMD(17 ) and CGI severity ratings in patients with major depression were yielded Simultaneous coexistence of anxiety with depressive disorders is probably one of the major current problems in Medicine . The pharmacological approach for Panic Disorder and Major Depression includes " high-powered " benzodiazepines for the rapid , but transitory relief of same symptoms and especially antidepressant compounds . Recently physical-instrumental approaches have been tested for the treatment of these complex diseases , like Cranial Electrotherapy Stimulation ( CES ) , Trans-cranial Magnetic Stimulation ( TMS ) , and Radio Electric Asymmetric Treatment ( REAC ) . The REAC apparatus was design ed to deliver an alternate current of several hundred picoamperes for a time span of 0.5 seconds by means of a small metallic probe directly connected to the properly fabricated electronic circuit in an AC/RF generator with frequency of 2.4 , 5.8 or 10.5 GHz and power of 20 mW. Compared the efficacy of  REAC  and Es-Citalopram in the treatment of simultaneous coexistence of Panic Disorder with Major Depression in 9-weeks open label naturalistic study . After the 1st week , patients treated with  REAC therapy  showed a significant relief of depressive symptoms compared with Es-Citalopram .  For Panic Disorder ,  REAC treatment had more effective results than the drug especially after the 3rd week of observation . The REAC treatment obtained better results during the entire study , and its high safety and tolerability profile has been confirmed OBJECTIVE Depression in older adults is often associated with cognitive abnormalities and may predict later development of a primary cognitive disorder . This double-blind , r and omized , placebo-controlled pilot study was design ed to assess the safety and efficacy of galantamine augmentation of antidepressant treatment for depressive and cognitive symptoms in older adults with major depression . METHODS Thirty-eight , non-demented older adults ( age > 50 ) with major depression were r and omized to receive galantamine or placebo augmentation of st and ard antidepressant pharmacotherapy ( venlafaxine XR or citalopram ) .  Mood and cognitive status were monitored for 24 weeks using the 24-item Hamilton Rating Scale for Depression and the Repeatable Battery for the Assessment of Neuropsychological Status . RESULTS Both groups showed significant improvements in mood and cognition over 24 weeks , but no significant difference was found in change over time between groups . An exploratory post-hoc analysis suggested that patients r and omized to galantamine had lower depression scores compared to patients in the placebo group after 2 weeks of treatment . Dropout was high with more subjects r and omized to antidepressant plus galantamine  withdrawing early from the study . CONCLUSIONS This pilot study failed to demonstrate a benefit for galantamine augmentation of antidepressant medication in the treatment of depression in older adults . Future studies should explore strategies for reducing dropout in such longitudinal trials and more carefully assess time to response with cholinesterase inhibitor augmentation OBJECTIVE To evaluate the efficacy of rEEG( ® )-guided pharmacotherapy for the treatment of depression in those circumstances where rEEG and STAR*D provided different recommendations . MATERIAL S AND METHODS This was a r and omized , single-blind , parallel group , 12 center , US study of rEEG-guided pharmacotherapy vs. the most effective treatment regimens reported in the NIH sponsored STAR*D study . Relatively treatment-resistant subjects ≥18 years who failed one or more antidepressants were required to have a QIDS-16-SR score ≥13 and a MADRS score ≥26 at baseline . All subjects underwent a washout of all current medications ( with some protocol -specified exceptions ) for at least five half-lives before receiving a QEEG and rEEG report . Subjects r and omized to rEEG were assigned a regimen based on the rEEG report . Control subjects who had failed only SSRI 's in their current episode were r and omized to receive venlafaxine XR .  Control subjects who had failed antidepressants from ≥2 classes of antidepressants were r and omized to receive a regimen from Steps 2 - 4 of the STAR*D study . Treatment lasted 12 weeks . The primary outcome measures were change from baseline for self-rated QIDS-SR16 and Q-LES-Q-SF . RESULTS A total of 114 subjects were r and omized and 89 subjects were evaluable . rEEG-guided pharmacotherapy exhibited significantly greater improvement for both primary endpoints , QIDS-SR16 ( -6.8 vs. -4.5 , p<0.0002 ) and Q-LES-Q-SF ( 18.0 vs. 8.9 , p<0.0002 ) compared to control , respectively , as well as statistical superiority in 9 out of 12 secondary endpoints . CONCLUSIONS These results warrant additional studies to determine the role of rEEG-guided psychopharmacology in the treatment of depression . If these results were confirmed , rEEG-guided pharmacotherapy would represent an easy , relatively inexpensive , predictive , objective office procedure that builds upon clinical judgment to guide antidepressant medication choice BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness This placebo-controlled , double-blind , 1-year pilot study aim ed at investigating possible clinical advantages of combining initial light therapy with the selective serotonin reuptake inhibitor ( SSRI ) citalopram as well as the effects of continuous long-term administration of this drug in patients with seasonal affective disorder ( SAD ) . Eight physically healthy women who met the DSM-III-R criteria for SAD were included in the study . Four women were r and omized to the citalopram group receiving 40 mg citalopram daily from the first of 10 light treatment days and throughout the 1-year study . The remaining four women were allocated to the placebo group using the same double-blind repeated measures design . The clinical outcome was measured by using three versions of the Comprehensive Psychopathological Rating Scale ( CPRS ) and Visual Analog Scales ( VAS ) , respectively . Taking the initial rating scores into account in covariance analyses , no statistically significant group difference was found during the light treatment period . However , during the follow-up period the full version of the CPRS and the self-rating version of CPRS and the VAS-scales for global condition and depressed mood were statistically significantly lower in the citalopram group compared with the placebo group . Thus , in this small but carefully observed sample of SAD- patients combining initial light therapy and long-term citalopram treatment was clinical ly more effective over time than the placebo combination . Our findings support the notion that light therapy with concomitant and continued SSRI ( citalopram ) treatment is a useful strategy to achieve beneficial long-term effects in patients with the SAD syndrome Purpose : Panic attacks may represent additional therapeutic problems in the elderly . The utility of citalopram in panic attacks has been widely investigated . Here , we compare the efficacy and safety of citalopram , with its S-enantiomer escitalopram at half dosage as to citalopram , in elderly patients who have panic attacks . Methods : This was an open community-based study . Forty patients who have panic attacks , according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria , were enrolled . Fifty percent of the patients were assigned for 8 weeks ' treatment with escitalopram , and the remaining 50 % were assigned to treatment with citalopram . The primary outcome measure was the weekly rate of panic attacks . The secondary outcome measures were the Hamilton scale for anxiety and depression and the Cooper Disability Scale . Analysis of variance by repeated measures was applied to calculate differences between groups . Results : A similar decrease in weekly rate of panic attacks , in the scores of Hamilton Scale for anxiety and depression and in the Cooper Disability Scale scores , was observed in both groups after 8 weeks , but a significant variation of outcome measures from baseline was observed already after 2 weeks in the escitalopram group ( P < 0.001 ) and only after 4 weeks in the citalopram group ( P < 0.01 ) . Conclusions : Escitalopram could be considered among the drugs of first choice in elderly patients with panic attacks because of its good efficacy and safety and for the advantage of reducing the total dose and of a more rapid onset of action as compared with citalopram , although further studies are needed to confirm these results BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day in elderly patients with major depression according to DSM-IV criteria . METHODS A r and omised , double-blind , parallel group 6-month study . Efficacy was assessed by MADRS , CGI Global Improvement , CGI Severity of Illness and GDS-20 scores and safety by physical examinations , vital signs , adverse events and UKU side effect rating . Plasma levels of venlafaxine , its major metabolite O-desmethylvenlafaxine and citalopram were followed . RESULTS One hundred and fifty-one male and female patients ( 64 - 89 years ) were enrolled and 118 patients completed the study . Comparable improvements in MADRS , CGI Severity of Illness , CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment . The MADRS remission rate was 19 % for venlafaxine and 23 % for citalopram .  Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment . There were no clinical ly significant changes in blood pressure or body weight . CONCLUSION The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects . Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram BACKGROUND Escitalopram is the single isomer responsible for the serotonin reuptake inhibition produced by the racemic antidepressant citalopram . The present r and omized , double-blind , placebo-controlled , fixed-dose multicenter trial was design ed to evaluate the efficacy and tolerability of escitalopram in the treatment of major depressive disorder . METHOD Out patients with an ongoing DSM-IV major depressive episode ( N = 491 ) were r and omly assigned to placebo , escitalopram , 10 mg/day , escitalopram , 20 mg/day , or citalopram , 40 mg/day , and entered an 8-week double-blind treatment period following a 1-week single-blind placebo lead-in . Clinical response was evaluated by the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the 24-item Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) scales , the Hamilton Rating Scale for Anxiety ( HAM-A ) , and patient-rated quality -of-life scales . RESULTS Escitalopram , at both doses , produced significant improvement at study endpoint relative to placebo on all measures of depression ; significant separation of escitalopram from placebo was observed within I week of double-blind treatment . Citalopram treatment also significantly improved depressive symptomatology compared with placebo ; however , escitalopram , 10 mg/day , was at least as effective as citalopram , 40 mg/day , at endpoint . Anxiety symptoms and quality of life were also significantly improved by escitalopram compared with placebo . The incidence of discontinuations due to adverse events for the escitalopram 10 mg/day group was not different from the placebo group ( 4.2 % vs. 2.5 % ; p = .50 ) , and not different for the escitalopram 20 mg/day group and the citalopram 40 mg/day group ( 10.4 % vs. 8.8 % ; p = .83 ) . CONCLUSION Escitalopram , a single isomer SSRI , is well-tolerated and has demonstrated antidepressant efficacy at a dose of 10 mg/day BACKGROUND Intravenous administration is often beneficial in the treatment of severely depressed patients . It is mainly the tri- and tetracyclic antidepressant drugs that can be administered intravenously . However , these drugs have a less favourable safety profile than newer antidepressants , such as the selective serotonin reuptake inhibitors ( SSRIs ) . Citalopram is the only SSRI that is available in a formulation for infusion . This double-blind , r and omised , multicentre trial was design ed to compare the efficacy and tolerability of citalopram infusion ( 40 mg per day ) and citalopram tablet ( 40 mg per day ) . METHODS Patients were r and omised to receive either placebo tablet plus citalopram infusion ( the infusion group ; n=135 ) or citalopram tablet plus placebo infusion ( the tablet group ; n=119 ) . After receiving r and omised treatment for eight days , all patients entered an open treatment phase , during which they received oral citalopram 40 mg per day for five weeks . RESULTS Although there was no difference in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores at the end of the r and omised treatment period , by the end of the open treatment phase the reduction in MADRS scores was significantly greater in the infusion group than in the tablet group ( p=0.015 ) . The infusion group also showed superior efficacy in Clinical Global Impressions assessment s. Citalopram was equally well tolerated in both treatment groups . CONCLUSIONS This trial confirmed the efficacy of citalopram 40 mg per day , and clearly supports the use of citalopram infusion in the treatment of severely depressed , hospitalised patients BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions Rationale and objective Depression is a significant complication of stroke . The effectiveness of antidepressant drugs in the management of post-stroke depression ( PSD ) has been widely investigated . However , the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies . Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor ( SSRI ) , citalopram , and a noradrenaline reuptake inhibitor ( NARI ) , reboxetine , in post-stroke patients affected by anxious depression or retarded depression . Methods This was a r and omized double-blind study . Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table . R and omisation was planned so that 50 % of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50 % were assigned to treatment with reboxetine . The Beck Depression Inventory ( BDI ) , the Hamilton Depression Rating Scale ( HDRS ) and a synoptic table were used to score depressive symptoms . Results Both citalopram and reboxetine showed good safety and tolerability . Citalopram exhibited greater efficacy in anxious depressed patients , while reboxetine was more effective in retarded depressed patients . Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects . In addition , PSD patients should be classified according to their clinical profile ( similarly to patients affected by primary depression ) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients OBJECTIVE Depressed mothers of children with psychiatric illness struggle with both their own psychiatric disorder and the dem and s of caring for ill children . When maternal depression remains untreated , mothers suffer , and psychiatric illness in their offspring is less likely to improve . This r and omized , controlled trial compared the interpersonal psychotherapy for depressed mothers ( IPT-MOMS ) , a nine-session intervention based on st and ard interpersonal psychotherapy , to treatment as usual for depressed mothers with psychiatrically ill offspring . METHOD Forty-seven mothers meeting DSM-IV criteria for major depression were recruited from a pediatric mental health clinic where their school-age children were receiving psychiatric treatment and r and omly assigned to IPT-MOMS  ( N=26 ) or  treatment as usual  ( N=21 ) . Mother-child pairs were assessed at three time points : baseline , 3-month follow-up , and 9-month follow-up . Child treatment was not determined by the study . RESULTS Compared to subjects assigned to treatment as usual , subjects assigned to IPT-MOMS showed significantly lower levels of depression symptoms , as measured by the Hamilton Depression Rating Scale , and higher levels of functioning , as measured by the Global Assessment of Functioning , at 3-month and 9-month follow-ups . Compared to the offspring of mothers receiving treatment as usual , the offspring of mothers assigned to IPT-MOMS showed significantly lower levels of depression as measured by the Children 's Depressive Inventory at the 9-month follow-up . CONCLUSIONS Assignment to IPT-MOMS was associated with reduced levels of maternal symptoms and improved functioning at the 3- and 9-month follow-ups compared to treatment as usual . Maternal improvement preceded improvement in offspring , suggesting that maternal changes may mediate child outcomes Numerous studies have assessed the acute efficacy of antidepressants , including selective serotonin reuptake inhibitors , in treating dysthymic disorder ; however , escitalopram , the S-enantiomer of citalopram , has not been studied . Thirty-six out patients with Structured Clinical Interview for DSM-III-R-diagnosed dysthymic disorder , aged 23–65 years ( mean±SD=44.7±11 years ) , were r and omly assigned to double-blind escitalopram ( maximum dose 20 mg/day ) versus placebo for 12 weeks . Inclusion criteria included age 18–65 years and Hamilton Depression Rating Scale ( HDRS ) score ≥12 . We hypothesized that escitalopram would be superior to placebo in the HDRS-24 item total score at week 12 . We also hypothesized the superiority of escitalopram over placebo for secondary measures , including the percentage of participants classified as responders and remitters , as well as social functioning ( Social Adjustment Scale ) , clinical global impression-improvement , Global Assessment of Functioning Scale . Participants ' baseline HDRS-24 averaged 23.4±5.9 . Final HDRS-24 scores at last observation carried forward did not differ significantly between escitalopram-treated  ( mean±SD=10.88±5.83 ) and placebo-treated  individuals ( mean±SD=16.4±6.34 ) ( F=2.82 , degrees of freedom=1,32 , P=0.10 ) . Significant differences favoring active medication were found on the Social Adjustment Scale and the Clinical Global Impression Severity and Global Assessment of Functioning Scale , but not in the percentages of responders or remitters . A larger study sample or higher escitalopram dose may show more significant placebo – medication differences UNLABELLED Depressive disorders in people older than 65 years seem to be a serious medical and social problem in many countries . The aim of the study was to evaluate efficiency and safety of citalopram and venlafaxine in treatment of depression in elderly patients . MATERIAL AND METHODS 89 elderly patients with a serious depressive episode were involved in the study . Observation was carried out for 42 days . The clinical state of patients was assessed by Hamilton rating scale ( HAM-D ) , a geriatric depressive scale ( GDS ) and a clinical general impression scale ( CGI ) . Cognitive functions were examined by Mini-Mental scale . 44 patients took citalopram , and 45 patients took venlafaxine . RESULTS On the 42nd day of treatment , citalopram therapy appeared successful in 34 ( 77.3 % ) patients , while venlafaxine therapy was successful in 30 ( 66.6 % ) patients . Citalopram was significantly more efficient than venlafaxine during the first 21 and 28 days of treatment . Neither drug caused disturbances of cognitive functions in the examined groups . CONCLUSIONS 1 . Citalopram and venlafaxine are similarly efficient in treatment of depressive disorders and are well tolerated by elderly patients . 2 . The onset of therapeutic activity of citalopram is potentially faster in depressive patients older than 65 years Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials After 1 mg DST , 25 major depressive patients ( DSM-III ) received at r and om either a specific inhibitor of noradrenaline reuptake ( Maprotiline ) or an inhibitor of serotinin reuptake ( Indalpine or Citalopram ) . After at least 3 weeks of treatment , no difference was found in treatment response between suppressors and non suppressors . This study is unable to confirm the usefulness of the DST in selection of treatment according to its central activity on serotonin or noradrenaline-reuptake Rationale S-citalopram ( escitalopram ) is the very active moiety of citalopram . It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder ( MDD ) . Objective The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients . Methods In the double-blind study , 240 MDD patients were r and omly assigned to treatment for 6 weeks either with escitalopram ( 10–20 mg/d ) or citalopram ( 20–40 mg/d ) . The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale ( HAMD-17 ) total score from baseline to the end of study . The secondary efficacy measurements were response and remission rates . The adverse events ( AEs ) were recorded by the investigator . Results Two hundred and three ( 85 % ) patients completed the trial . The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group . No significant differences were found between the two groups in the change in HAMD-17 total score , response , and remission rate . These results were similar in severe MDD patients . No significant differences were found between the two groups in AEs . No serious AEs were observed in this study . Conclusions The study suggests that escitalopram 10–20 mg/d are as effective and safe as citalopram 20–40 mg/d in the short-term treatment for Chinese MDD patients OBJECTIVE There is increasing evidence that cerebrovascular factors play a key role in the etiology of  late-life depression .  This study examined the severity of subcortical hyperintensities ( SH ) and the relationship between SH and depression characteristics in two sample s of elderly depressed out patients differing in age . METHODS The sample s consisted of 59 subjects age 60 and over , ( 69+/-5.6 years ) , who participated in a trial of sertraline , and 111 subjects age 75 and over , ( 79+/-4.1 years ) , who participated in a trial of citalopram .  RESULTS The citalopram group was significantly older than the sertraline group and had more severe SH ( 72 % vs. 42 % high ratings ) . The High SH group was significantly older than the Low SH group in the sertraline study but there was no difference in age in the SH groups in the citalopram sample . There was no relationship between SH severity and baseline depression or age of onset . However , age strongly correlated with later age of onset . There was no relationship between SH severity and cardiovascular risk factors or treatment response in the sertraline sample . CONCLUSION Age is a major factor for the development of SH and late-life depression . There may not be an association between SH and depression severity , cardiovascular risk factors , or treatment response in geriatric depressed out patients . The etiologic factors and clinical course of late-life depression requires further study Pretreatment plasma ratios of tryptophan ( Trp ) and tyrosine ( Tyr ) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram , a selective serotonin uptake inhibitor , against maprotiline , a selective noradrenaline uptake inhibitor .  The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls . Plasma Tyr ratio was normal in the endogenous , but significantly decreased in the non-endogenous depressives . There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF , or between the plasma Tyr ratio and HVA level in CSF , whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio . There was a significantly positive correlation between the Trp ratio , the Tyr ratio , their sum and the final Hamilton depression score in 14 patients treated with citalopram ; on the whole , this association was evident also in the endogenous and non-endogenous subgroups . In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score ; this association was poor in the endogenous , whereas a trend towards a correlation remained in the non-endogenous subgroup . The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline . However , further studies are needed on larger patient sample s to allow a firm conclusion BACKGROUND Isolated reports suggest that escitalopram may be effective for impulsive-compulsive Internet usage disorder ( IC-IUD ) , an impulse-control disorder characterized by excessive time spent on the Internet at the expense of occupational , relationship , and social activities . To assess the safety and efficacy of escitalopram in IC-IUD , we conducted a 10-week , open-label trial followed by a 9-week , double-blind , placebo-controlled discontinuation phase . METHOD From December 2002 to October 2004 , 19 adult subjects with IC-IUD ( defined as time consuming , uncontrollable , distressing , and result ing in social , occupational , or financial difficulties ) were enrolled .  Escitalopram was started at 10 mg/day , then increased and maintained at 20 mg/day for 10 weeks at the end of which completers were r and omly assigned to placebo or escitalopram for 9 additional weeks . Two key outcome measures were used : hours spent weekly in nonessential Internet use and overall clinical response ( subjects rated " much improved " or " very much improved " on the Clinical Global Impressions-Improvement scale [ CGI-I ] ) . RESULTS Fourteen subjects completed the entire study . At the end of the 10th week of open-label esci-talopram , Internet usage decreased significantly from a mean of 36.8 hours/week at baseline to 16.5 hours/week ( paired t test : t = 3.58 ; p = .002 ) . In addition , 64.7 % of the sample ( N = 11 ) were considered CGI-I responders . At the end of the double-blind phase , there were no significant differences in outcome measures between patients taking placebo compared to escitalopram ( analysis of variance with repeated measures , p > .05 ) . CONCLUSION Patients showed a significant improvement of IC-IUD symptoms during the open-label escitalopram phase . There was no significant difference between the escitalopram and placebo groups at the end of the subsequent double-blind phase ; both groups maintained the gains made in the initial open-label treatment . Larger controlled trials are needed to investigate the efficacy of this and other pharmacologic agents in the treatment of IC-IUD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00565422 Abstract The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram ( 10mg/d ) versus clomipramine ( 25 mg/d ) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors ( SSRIs ) . Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision , MDE and partial or no response to SSRIs per os ( 21-item Hamilton Depression Rating Scale [ HAM-D21 ] score reduction , < 50 % or ≤25 % , respectively , compared with pretreatment scores ) were selected and r and omized to citalopram ( n = 18 ) , clomipramine ( n = 18 ) , or placebo ( n = 18 ) intravenous augmentation . The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs . Analyses of variance with repeated measures on HAM-D21 , collected daily in blind-raters design , were performed to detect any change of depressive symptoms between the 3 groups . In addition , the number of responders and remitters was computed in the 3 groups of treatment . At end point , a significant treatment effect ( F= 4.57 ; P = 0.015 ) and time-by-treatment effect ( F = 11.22 ; P < 0.0001 ) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo , with a superiority of citalopram over clomipramine on overall symptoms ( P = 0.05 ) as well as on anxiety-somatization symptoms ( P = 0.027 ) . The number of responders was significantly superior in the active treatment groups versus the placebo group ( χ22 = 16.36 ; P < 0.0001 ) . The same result was found , considering the number of remitters ( χ22 = 13.50 ; P < 0.0001 ) . Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior  to  placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms . The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results , and larger r and omized controlled trials are warranted to confirm the present findings & NA ; Two selective serotonin reuptake inhibitors ( SSRIs ) , citalopram and fluoxetine , both at a daily dose of 20 mg , were compared in patients with unipolar major depression treated in general practice . This was a multicentre , double‐blind , r and omized trial carried out in France . The duration of treatment was 8 weeks . Patients were assessed by means of the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) , the 17 items Hamilton Depression Rating Scale ( HAMD ) and the investigator 's Clinical Global Impressions ( CGI ) . Observed and spontaneously reported adverse events were also recorded . A total of 357 patients of both sexes , aged between 21 and 73 years , entered the double‐blind phase of the trial . A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments . Apart from back pain recorded more frequently in the citalopram group , no significant difference was found between the two treatment groups with regard to adverse events , and both citalopram and fluoxetine were considered to be well tolerated . It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression . Citalopram showed an earlier onset of recovery than fluoxetine OBJECTIVE This study determined the efficacy of antidepressant medication for the treatment of depression in the " old-old . " METHOD This r and omized 8-week medication trial compared citalopram , 10 - 40 mg/day , to placebo in the treatment of patients 75 and older with unipolar depression . RESULTS A total of 174 patients who were 58 % women with a mean age of 79.6 years ( SD=4.4 ) and a mean baseline Hamilton Depression Rating Scale score of 24.3 ( SD=4.1 ) were r and omly assigned to treatment at 15 sites . There was a main effect for site but not for treatment condition . The remission rate , defined as a final Hamilton depression scale score < 10 , was 35 % for the citalopram and 33 % for the placebo groups . However , patients with severe depression ( baseline Hamilton depression scale score > 24 ) tended to have a higher remission rate with medication than with placebo ( 35 % versus 19 % ) . CONCLUSIONS In the oldest group of community-dwelling patients to be studied to date , medication was not more effective than placebo for the treatment of depression . However , given the considerable psychosocial support received by all patients , the placebo condition represents more than the ingestion of an inactive pill . Across sites , there was considerable range in response to medication , 18 % to 82 % , and to placebo , 16 % to 80 % Increased levels of inflammatory cytokines such as tumor necrosis factor ( TNF ) and interleukin-6 ( IL-6 ) may play a role in depression . Mild depressive-like symptoms can be induced in humans through activation of the innate immune system with endotoxin . Whether preventive treatment with antidepressants can reduce endotoxin-induced symptoms has never been tested . In a double-blind , r and omized , placebo-controlled , cross-over study , we administered intravenous low-dose endotoxin ( 0.8 ng/kg ) or placebo to 11 healthy subjects who had received oral pre-treatment with citalopram ( 10 mg twice a day ) or placebo for 5 days . The Montgomery-Åsberg Depression Rating Scale , the State and Trait Anxiety Inventory , and a visual analog scale were used to measure depressive and anxiety symptoms and social anhedonia . Serum levels of TNF and IL-6 were measured with immunoassays . Compared to placebo , endotoxin administration increased serum levels of TNF and IL-6 , and caused mild depressive-like symptoms , in particular lassitude and social anhedonia . While citalopram pre-treatment had no effect on the innate immune response to endotoxin , it reduced the endotoxin-induced MADRS total score by 50 % , with a moderate effect size ( Cohen 's d=0.5 ) . Most of the MADRS total score was due to the lassitude item , and citalopram pre-treatment specifically reduced endotoxin-induced lassitude with a large effect size ( Cohen 's d=0.9 ) . These results suggest that subchronic pre-treatment with the serotonin-reuptake inhibitor citalopram blunts mood symptoms induced by acute immune system activation with endotoxin without inhibiting the peripheral immune response This double-blind , r and omised , multicentre study compared the antidepressant efficacy and safety of two doses of milnacipran ( 100 mg/day and 200 mg/day ) and fluoxetine ( 20 mg/day ) in 289 in patients with endogenous depression . After a placebo washout period of 4–7 days , assessment s were performed weekly during ; the first 4 weeks , and then after 6 , 8 and 12 weeks , using the 17-itein Hamilton Depression Rating Scale ( HDRS ) . the Montgomery - Åsberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression ( CGI ) . HDRS total score was reduced by a mean of 14.8 in the milnacipran 100 mg/day group , 12.9 in the milnacipran 200 mg/day group and 12.1 in the fluoxetine  20 mg/day group . MADRS total score decreased by 17.4 , 15.8 and 14.6 , respectively . No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores . However , the time-by-time change showed a trend in favour of milnacipran 100 mg/day , which was found significantly superior to fluoxetine at day 28 for several converging parameters ( MADRS , CGI-3 ) . Overall , efficacy ratings for all parameters were highest for milnacipran 100 mg/day , followed by milnacipran 200 mg/day and fluoxetinc 20 mg/day . Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase hi heart rate ≥ 100 bpm in milnacipran recipients and a significantly greater weight loss in fluoxetine recipients OBJECTIVE Selective serotonin reuptake inhibitors are commonly used to treat major depression ; however , the percentage of serotonin ( 5-HT ) transporter ( 5-HTT ) sites occupied during clinical dosing is unknown . This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked . METHOD Twelve medication-free depressed patients completed a 6-week trial of either paroxetine ( N=8 ) or citalopram ( N=4 ) . Striatal 5-HTT binding potential was measured with [(11)C]DASB and positron emission tomography , before and after 4 weeks of treatment . The binding potential is proportional to receptor density . Striatal 5-HTT binding potential was measured twice in six healthy subjects and once in 11 healthy subjects . RESULTS A significant decrease in striatal 5-HTT binding potential was found after either treatment , compared to changes found over a 4-week period in healthy subjects . For patients treated with 20 mg/day of paroxetine ( N=7 ) , the mean proportion of 5-HTT sites occupied was 83 % . For patients treated with 20 mg/day of citalopram ( N=4 ) , the mean 5-HTT occupancy was 77 % . 5-HTT occupancy increased in a nonlinear relationship with serum levels of paroxetine such that a plateau of occupancy around 85 % occurred for serum paroxetine levels greater than 28 microg/liter . CONCLUSIONS During treatment with clinical doses of paroxetine or citalopram , approximately 80 % of 5-HTT receptors are occupied . This change in 5-HTT binding potential is greater than the known physiological range of changes in 5-HTT binding potential but may be necessary for some therapeutic effects Objective : The aim of this single‐blind study was to examine the efficacy and tolerability of citalopram compared to nortriptyline in moderate to severe major depressive patients aged 60 years or over OBJECTIVE Phase III clinical trials for depression enroll participants with major depressive disorder according to stringent inclusion and exclusion criteria . These patients may not be representative of typical depressed patients seeking treatment . This analysis used data from the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) project -- which used broad inclusion and minimal exclusion criteria --to evaluate whether phase III clinical trials recruit representative depressed out patients . METHOD Of 2,855 participants , 22.2 % met typical entry criteria for phase III clinical trials ( efficacy sample ) and 77.8 % did not ( nonefficacy sample ) . These groups were compared regarding baseline sociodemographic and clinical features and the characteristics and outcomes of acute-phase treatment . RESULTS The efficacy sample had a shorter average duration of illness and lower rates of family history of substance abuse , prior suicide attempts , and anxious and atypical symptom features . Despite similar medication dosing and time at exit dose , the efficacy participants tolerated citalopram better . They also had higher rates of response ( 51.6 % versus 39.1 % ) and remission ( 34.4 % versus 24.7 % ) . These differences persisted even after adjustments for baseline differences . CONCLUSIONS Phase III trials do not recruit representative treatment-seeking depressed patients . Broader phase III inclusion criteria would increase the generalizability of results to practice , potentially reducing placebo response and remission rates ( reducing the risk of failed trials ) but at the risk of some increase in adverse events It has been hypothesized that non-rapid eye movement ( NREM ) sleep facilitates declarative memory consolidation , and rapid eye movement ( REM ) sleep is particularly important in promoting procedural learning . The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks . For our baseline , we chose 41 moderately depressed patients ( age range 19 - 44 years ) , who were not taking antidepressants .  In the morning after polysomnography , we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency , a shift of attention task and the Trail Making Test B. After recording baseline values , patients were assigned r and omly to one of three treatment groups : medication with citalopram ; medication with reboxetine ; or exclusive treatment with psychotherapy . Retesting took place 1 week after onset of treatment . The main results were : ( 1 ) an association of slow-wave sleep with verbal memory performance at baseline ; ( 2 ) a suppression of REM sleep in patients taking citalopram and reboxetine ; ( 3 ) no differences regarding neuropsychological performance within the treatment groups ; and ( 4 ) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine . In line with other studies , our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants ABSTRACT Objective : A r and omized , double-blind , 24‐week fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was conducted in primary care patients with moderate to severe major depressive disorder ( MDD ) . Research design and methods : This was a r and omized , double-blind , 24‐week fixed-dose study . Patients were r and omly assigned to treatment with escitalopram 10 mg/day ( n = 175 ) or citalopram 20 mg/day ( n = 182 ) . Clinical response was evaluated using the Montgomery – Åsberg Depression Rating Scale ( MADRS ) and Clinical Global Impression-Severity ( CGI‐S ) scale . The prospect ively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment , using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously . Results : Based on the primary parameter , escitalopram was at least as efficacious as citalopram . Based on the prospect ively defined secondary parameter , mean change from baseline in the CGI‐S score  , escitalopram was statistically significantly superior to citalopram at Week 24 . The importance of long-term treatment could be demonstrated , in that more than half ( 55 % and 51 % ) of the patients who had not responded by Week 8 achieved remission by Week 24 . Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment , and the overall adverse event profiles for the two drugs were similar . For the intent-to-treat population , there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group , particularly after Week 8 . Conclusion : Patients with MDD responded well to long-term treatment with either escitalopram or citalopram . This study demonstrated the importance of extending treatment of depression beyond 8 weeks This paper investigates if the highly selective norepinephrine reuptake inhibitor reboxetine leads to a dose-dependent cortisol release and if this response depends on personality dimensions related to clinical depression in healthy volunteers . Twenty-four male subjects received placebo , 2 mg , or 4 mg reboxetine in a balanced , r and omized cross-over study . Cortisol was measured in saliva at six different time-points according to the kinetics of the drug . Furthermore , several measurements of cardiovascular parameters , emotional states , and possible side-effects were obtained . Subjects were divided into two groups scoring above or below the median of a depressiveness question naire scale [ n = 11 , low ( D- ) ; n = 13 , high ( D+ ) ] . Results clearly demonstrated , that reboxetine stimulates cortisol release . Whereas blood pressure was not affected , heart rate increased after 2 and 4 mg but not dose dependently . Subjects reported more non-specific arousal while the dimensions of tiredness-wakefulness and positive-negative emotional states were not affected by the drug . Somatic complaints were low and only non-specific complaints were statistically elevated but of negligible amount . Subjects classified as D+ can be characterized as high responders to the drug . This is especially true not only for cortisol increases but also for changes in heart rate and some ratings on physical complaints . Hot flushes , sweating and a throbbing sensation in blood vessels in the head were observed in D+ but only with the 4 mg dose . The results clearly demonstrate that reboxetine stimulates cortisol release and heart rate and that this is particularly pronounced in subjects scoring high on depression-related personality dimensions . Reboxetine , therefore , is a promising tool for investigating neuroendocrine response to noradrenergic challenge tests . The question whether increased responses in D+ are due to an up-regulation of receptor sensitivity as a consequence of low norepinephrine supply is discussed The response of patients with major depressive illness to citalopram of amitriptyline was compared in a double-blind multi-centre trial . No differences in efficacy were observed , but citalopram had less hypnotic effect , and a remarkably lower profile of side-effects St. John 's Wort ( Hypericum perforatum L. ) is a useful medication in the treatment of mild to moderate depression . By re analysis of the data obtained from a total of 154 patients , who responded in a r and omised , multicentric , double-blind , placebo-controlled study , to 6 weeks of treatment for an episode of moderate depression with either 20 mg citalopram or 900 mg Hypericum extract STW 3-VI , the duration of response and occurrence of relapse/recurrence were evaluated . Duration of response and occurrence of relapse/recurrence was measured by re-evaluating the responders in a controlled- clinical trial ( final score of ≤10 according to HAMD at the end of the clinical trial ) according to the Hamilton Rating Scale for Depression ( HAMD ) . In total , 30 ( 19.5 % ) of the 154 responders were diagnosed with a relapse . The numbers of patients with relapses were highest in the citalopram group ( 14 of 54 ) , whereas patients who were treated with Hypericum extract STW 3-VI showed the lowest relapse rate ( 8/54 ) ; patients from the placebo group showed a relapse rate of 8/46 . No difference in the severity of relapse could be observed . The duration of response was longest for the Hypericum group ( 1817 days ) , intermediate for the citalopram group ( 1755 days ) and shortest for the placebo group ( 802 days ) . Hypericum extract STW 3-VI is more efficient in lowering the relapse and recurrence rates of responders , when compared to citalopram and placebo . In addition , duration of response was increased in the group treated with Hypericum extract STW 3-VI BACKGROUND The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants . The aim of the study was to compare the costs and outcomes of using amitriptyline , citalopram and fluoxetine in the treatment of major depression . METHODS Ninety patients ( 69 women ) with a mean age of 44.5 years ( S.D. = 14.3 ) suffering from major depression were treated with amitriptyline ( N = 31 ) , citalopram ( N = 29 ) and fluoxetine ( N = 30 ) . Direct medical costs and effectiveness ( indicated by the number of hospitalization-free days ) were assessed in a prospect i ve , open , intent-to-treat study . RESULTS Neither cost nor effectiveness were significantly different among the treatment groups . CONCLUSION Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies . There is no advantage in restricting patients from treatment with SSRIs , which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The  dropout number  was 91 in the  reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects .  Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6  Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine  in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD .  Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure " adrenergic " and the other pure " serotonergic . " A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs ) The purpose of this double-blind , multicenter trial was to compare the efficacy and safety of sertraline ( 50–150 ing/day ) with those of citalopram ( 20–60 mg/day ) in patients with major depression in general practice during 24 weeks of treatment . The patients were assessed using the Montgomery-Åsberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales . Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale .  Altogether 400 patients were r and omized into the study . A total of 308 patients completed the 24-week study in accordance with the protocol . A significant reduction in the total Montgomery-Åsberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks , with no statistically significant differences between the drugs . In the intention to treat-lust observation carried forward analysis 76 % responded to treatment in the sertraline and 81 % in the citalopram group . The final mean doses were 82 mg/day ( 64 % higher than baseline ) in the sertraline group and 34 mg/day ( 70 % higher than baseline ) in the citalopram group . The response rate in completers in accordance with protocol was 90 % in the sertraline group and 93 % in the citalopram group . The side-effects were those usually seen , and both sertraline and citalopram were considered to be well tolerated . It was concluded that patients with major depression in general practice  respond well to 24 weeks of treatment with sertraline or citalopram . With regard to efficacy , no statistically significant differences were found between the drugs OBJECTIVE Prescribing recommendations specify that lamotrigine should ordinarily be discontinued at the first sign of rash , regardless of its type and severity , unless the rash is clearly not drug related . This practice helps to ensure that lamotrigine is discontinued in instances of serious rash ( an event occurring in up to 0.13 % of cases in bipolar clinical trials ) but may lead to unnecessary discontinuation of lamotrigine for cases of nonserious rash arising from nondrug causes . Measures aim ed at reducing overall occurrence of dermatologic reactions might reduce the incidence of nonserious rash leading to premature lamotrigine discontinuation . This study assessed the impact of specific instructions design ed to decrease risk of dermatologic reactions , including nonserious rash , during initiation of and early treatment with lamotrigine in patients with bipolar I disorder . METHOD Out patients with DSM-IV-diagnosed bipolar I disorder > /= 13 years of age at 188 sites were r and omly assigned to receive Usual Care Pre caution s ( UCP ; pre caution s from the patient instructions in the prescribing information for reducing risk of rash including nonserious rash ) or Dermatologic Pre caution s ( DP ; pre caution s as above [ UCP ] plus additional pre caution s intended to decrease risk of any dermatologic reaction including nonserious rash ) during 12 weeks of adding open-label lamotrigine to concomitant medications . Patients with comorbid medical and psychiatric problems were not excluded unless , in the opinion of the investigators , these problems were sufficiently severe to preclude participation . Investigators and patients were blinded to which pre caution group patients were r and omly assigned . The primary outcome measure was the rate of rash during the treatment period . Secondary outcome measures included clinical response to lamotrigine  , assessed with the investigator- and self-rated Clinical Global Impressions-Bipolar version ( CGI-BP ) and the Clinical Global Impressions-Efficacy Index ( CGI-EI ) . Data were collected from August 2003 to August 2004 . RESULTS 867 ( 74 % ) of 1175 patients completed the study . Only 182 ( 15 % ) of 1175 patients had an adverse event leading to discontinuation of study medication or withdrawal , including 62 ( 5.3 % ) of 1175 due to non-serious rash . No serious rashes were reported during the study in either group . The incidence of nonserious rash was similarly low in patients with UCP and DP ( 8.8 % and 8.6 % , respectively ) . CGI-BP-Severity and -Improvement scores indicated mood improvement when lamotrigine was added to existing therapy , and CGI-EI scores at weeks 5 and 12 reflected a favorable balance between control of mood symptoms and tolerability . At both weeks 5 and 12 , investigators reported that therapeutic effects of additional lamotrigine outweighed side effects in 74 % of subjects . CONCLUSION UCP and DP yielded low , similar non-serious rash rates , which were marginally lower than nonserious rash rates in prior clinical trials that did not utilize DP but marginally higher than that in a prior open case series using DP . Nevertheless , the results are encouraging : in this large study reflecting real-world use , lamotrigine was well tolerated with no serious rash and low incidences of nonserious rash and discontinuation due to rash , and lamotrigine therapy was associated with clinical improvement in a heterogeneous cohort of patients with bipolar I disorder OBJECTIVES To evaluate clinical effectiveness at 4 weeks of antidepressant therapy for mothers with postnatal depression ( PND ) compared with general supportive care ; to compare outcome at 18 weeks of those r and omised to antidepressant therapy with those r and omised to listening visits as the first intervention ( both groups were to be allowed to receive the alternative intervention after 4 weeks if the woman or her doctor so decided ) ; and to assess acceptability of antidepressants and listening visits to users and health professionals . DESIGN A pragmatic two-arm individually r and omised controlled trial . SETTING Participants were recruited from 77 general practice s : 21 in Bristol , 21 in south London and 35 in Manchester . PARTICIPANTS A total of 254 women who fulfilled International Classification of Diseases version 10 criteria for major depression in the first 6 postnatal months were recruited and r and omised . INTERVENTIONS Women were r and omised to receive either an antidepressant , usually a selective serotonin reuptake inhibitor prescribed by their general practitioner ( GP ) , or non-directive counselling ( listening visits ) from a specially trained research health visitor ( HV ) . The trial was design ed to compare antidepressants with general supportive care for the first 4 weeks , after which women allocated to listening visits commenced their sessions . It allowed for women to receive the alternative intervention if they had not responded to their allocated intervention or wished to change to , or add in , the alternative intervention at any time after 4 weeks . MAIN OUTCOME MEASURES The duration of the trial was 18 weeks . Primary outcome , measured at 4 weeks and 18 weeks post r and omisation , was the proportion of women improved on the Edinburgh Postnatal Depression Scale ( EPDS ) , that is scoring < 13 . Secondary outcomes were the EPDS measured as a continuous variable at 4 and 18 weeks , and scores on various other question naires . RESULTS At 4 weeks , women were more than twice as likely to have improved if they had been r and omised to antidepressants compared with listening visits , which started after the 4-week follow-up , i.e. after 4 weeks of general supportive care [ primary intention-to-treat ( ITT ) , 45 % versus 20 % ; odds ratio ( OR ) 3.4 , 95 % confidence interval ( CI ) 1.8 to 6.5 , p < 0.001 ] . Explanatory analyses emphasised these findings . At 18 weeks , ITT analysis revealed that the proportion of women improving was 11 % greater in the antidepressant group , but logistic regression analysis showed no clear benefit for one group over the other [ 62 % versus 51 % , OR 1.5 ( 95 % CI 0.8 to 2.6 ) , p = 0.19 ] . Overall , there was a difference between the groups in favour of the antidepressant group of about 25 percentage points at 4 weeks , which reduced at 18 weeks . No statistical support existed for a benefit of antidepressants at 18 weeks , but 95 % CIs could not rule out a clinical ly important benefit . It was difficult for GPs not to prescribe antidepressants to women r and omised to listening visits after the initial 4 weeks , so many women received both interventions in both groups by 18 weeks and consequently power was reduced . Qualitative interviews with women revealed a preference for listening visits but an acceptance that antidepressants might be necessary . They wished to be reassured that their GP and HV were offering continuity of care focusing on their particular set of circumstances . Interviews with GPs and HVs revealed lack of collaboration in managing care for women with PND ; neither professional group was willing to assume responsibility . CONCLUSIONS At 4 weeks , antidepressants were significantly superior to general supportive care . Trial design meant that by 18 weeks many of the women initially r and omised to listening visits were also receiving antidepressants , and more vice versa . The lack of evidence for differences at 18 weeks is likely to reflect a combination of reduced power and the considerable degree of switching across the two interventions . Qualitative study revealed that women found both antidepressants and listening visits effective depending on their circumstances and preferences . The trial indicates that early treatment with antidepressants leads to clinical benefit for women with PND BACKGROUND Depression and chronic heart failure ( CHF ) are common conditions , both of which are clinical ly and economically highly relevant . Major depression affects 20 - 40 % of CHF patients and predicts adverse outcomes in terms of quality of life , morbidity and mortality as well as health care expenditure , independent of other factors of prognostic relevance . AIMS The purpose of the MOOD-HF trial is to clarify whether antidepressant pharmacotherapy improves outcome in CHF patients , and if so by which mechanism(s ) . METHODS MOOD-HF is a prospect i ve , r and omised , double-blind , placebo-controlled , 2-armed , parallel-group multicenter trial investigating the effects of the serotonin re-uptake inhibitor ( SSRI ) escitalopram on morbidity and mortality ( primary endpoint ) , severity of depression , anxiety , cognitive function , quality of life and health care expenditure in 700 patients with symptomatic systolic CHF and major depression diagnosed by structured clinical interview . All patients will receive optimised pharmacotherapy for CHF . Duration of follow-up , including close safety monitoring , is 12 - 24 months from r and omisation . PERSPECTIVE MOOD-HF is the first prospect i ve r and omised controlled trial to assess the effects of antidepressant pharmacotherapy  on hard somatic endpoints , the mechanism(s ) of action of SSRI treatment , as well as safety in New York Heart Association functional class II-IV CHF patients . The results are expected to promote the development of evidence -based recommendations for managing depression in the context of CHF . TRIAL REGISTRATION ( IS RCT N.org ) . Identifier : IS RCT N33128015 OBJECTIVE The present study investigated the efficacy and tolerability of escitalopram in the prevention of relapse of  major depressive disorder ( MDD ) in older patients who had responded to acute treatment with escitalopram .  METHOD A total of 405 patients who were aged 65 years or older with a primary diagnosis of MDD ( according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria ) and a Montgomery-Asberg Depression Rating Scale ( MADRS ) total score of 22 or more received 12-week , open-label escitalopram 10 or 20 mg per day treatment . Remitters ( MADRS < /=12 ) were r and omized to 24-week double-blind treatment with escitalopram or placebo . The primary efficacy parameter was the time to relapse , defined as either an increase in MADRS total score to 22 or more or lack of efficacy as judged by the investigator . RESULTS Three hundred five patients  achieved remission and were r and omly assigned to treatment with escitalopram ( N = 152 ) or placebo ( N = 153 ) . The primary analysis showed a clear beneficial effect of escitalopram relative to placebo on the time to relapse ( log-rank test , chi(2 ) = 27.6 , df = 1 , p < 0.001 ) . The risk of relapse was 4.4 times higher for placebo- than for escitalopram-treated patients ( chi(2 ) test , chi(2 ) = 22.9 , df = 1 , p < 0.001 ) . Significantly fewer escitalopram-treated patients relapsed ( 9 % ) compared with placebo ( 33 % ) ( chi(2 ) test , chi(2 ) = 27.1 , df = 1 , p < 0.001 ) . Escitalopram was well tolerated with 53 patients ( 13 % ) withdrawn as a result of adverse events during the open-label period and three ( 2 % ) escitalopram-treated patients and six ( 4 % ) placebo-treated patients during double-blind treatment ( not significant ) . The overall withdrawal rate , excluding relapses , was 7.2 % for escitalopram and 8.5 % for placebo during the double-blind period ( not significant ) . CONCLUSION Escitalopram was effective in preventing  relapse of MDD in older patients and was well tolerated as continuation treatment BACKGROUND It is estimated that major depressive disorder affects 0.9 % of community-dwelling older adults in the United States . However , as many as 18 % of older US adults reportedly suffer from depressive symptoms that do not necessarily fit the criteria for major depressive disorder ( eg , dysthmia , minor depression ) . OBJECTIVES The goals of this study were to describe patterns of antidepressant medication use in older adults with dysthymia or minor depression and to examine factors associated with the use of antidepressants at baseline . METHODS This was a secondary analysis using cross-sectional data collected during a r and omized controlled trial conducted from 2000 through 2003 . It involved community senior service agencies and in-home visits in Seattle , Washington . Adults aged > or=60 years who had minor depression or dysthymia and were receiving services through community senior service agencies or living in senior public housing were included . Study participants were classified as users or nonusers of antidepressants . Prescription medication use in the past 2 weeks was assessed at baseline and 6 and 12 months . Medication name , dose , and directions were recorded from the medication label . Logistic regression was used to examine variables associated with baseline antidepressant use . RESULTS A total of 138 patients ( mean age , 73.00 years ) were included ; the majority of study participants were female ( 779.00 % ) . Overall , 42.33 % were nonwhite ( 34.3 % black , 4.4 % Asian , 1.5 % American Indian/Alaskan Native , 0.7 % Hispanic , and 1.5 % other ) . At baseline , 36.2 % of study participants ( n = 50 ) were using antidepressants .  Selective serotonin reuptake inhibitors were the most common class of antidepressants , used by 62.00 % , 70.22 % , and 71.11 % of antidepressant users at baseline , 6 , and 12 months , respectively . However ,  nortriptyline  was the most common antidepressant at baseline , taken by 20.00 % of antidepressant users . Use of other prescription medications was associated with antidepressant use at baseline . CONCLUSIONS We found antidepressant use to be low in these relatively poor , community-dwelling , ethnically diverse older adults with dysthymia and minor depression in 2000 through 2003 , with 36.22 % of participants using antidepressants at baseline . Antidepressant users were more likely to be taking other prescription medications than nonusers OBJECTIVE Pain and depression are two of the most prevalent and treatable cancer-related symptoms , each present in at least 20 - 30 % of oncology patients . Both symptoms are frequently either unrecognized or undertreated , however . This article describes a telecare management intervention delivered by a nurse-psychiatrist team that is design ed to improve recognition and treatment of pain and depression . The enrolled sample is also described . METHODS The Indiana Cancer Pain and Depression study is a National Cancer Institute-sponsored r and omized clinical trial . Four hundred five patients with cancer-related pain and /or clinical ly significant depression from 16 urban or rural oncology practice s throughout Indiana have been enrolled and r and omized to either the  intervention group or to a  usual-care control group  . Intervention patients receive central ized telecare management coupled with automated home-based symptom monitoring . Outcomes will be assessed at 1 , 3 , 6 and 12 months by research assistants blinded to treatment arms . RESULTS Of 4465 patients screened , 2185 ( 49 % ) endorsed symptoms of  pain or depression . Of screen-positive patients , about one-third were ineligible ( most commonly due to pain or depression not meeting severity thresholds or to pain that is not related to cancer ) . Of the 405 patients enrolled , 32 % have depression only , 24 % have pain  only and 44 % have both depression and pain . At baseline , participants reported an average of 16.8 days out of the past 4 weeks during which they were confined to bed or had to reduce their usual activities by > or = 50 % due to pain or depression . Also , 176 ( 44 % ) reported being unable to work due to health reasons . CONCLUSIONS When completed , the Indiana Cancer Pain and Depression trial will test whether central ized telecare management coupled with automated home-based symptom monitoring improves outcomes in cancer patients with depression and /or pain . Findings will be important for both oncologists and mental health clinicians confronted with oncology patients ' depression or pain ABSTRACT — In a controlled , clinical , multicentre trial comprising a total of 43 patients ( 17 men and 26 women )  citalopram was compared double‐blindly with amitriptyline .  Nineteen patients of each group were classified as endogenously depressed , whereas four patients of the citalopram group and one of the amitriptyline group were classified as non‐endogenously depressed . The patients were seriously ill with a high frequency of previous depressive episodes and of mental disorders among their closest relatives . Thirteen of the patients in either group had received antidepressants without satisfactory effect before entry into the trial . Each patient was treated for a period of at least 3 weeks with daily citalopram doses of 30–60 mg or daily amitriptyline doses of 75–225 mg . A statistically significant reduction of MADRS scores ( total scores as well as each of the 10 individual items ) was recorded in both groups . The only difference between the groups was a trend towards a better effect on sleep disturbances in the amitriptyline group . Side‐effects were recorded more frequently in the amitriptyline group than in the citalopram group , global assessment of side effects being significantly different in favour of citalopram . It is concluded that citalopram is an effective and safe drug in the treatment of endogenous depression ‐ probably as efficacious as amitriptyline , but with fewer side effects This paper presents new data addressing two important controversies in psychiatry : the construct of Minor Depression ( MinD ) and the efficacy of St. John 's Wort for milder forms of depressive disorders . Data are from a three-arm , 12 week , r and omized clinical trial of investigating the efficacy of St. John 's Wort ( 810 mg/day ) , citalopram ( 20 mg/day ) , or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures , neither St. John 's Wort nor citalopram separated from placebo on change in depressive symptom severity , quality of life , or well-being . However , systematic assessment of potential adverse effects ( AEs ) led to three important observations : ( 1 ) prior to the administration of study compound , 60 % of subjects endorsed items that would be characterized as AEs once study compound was administered , ( 2 ) St. John 's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment , and ( 3 ) using a structured interview for identifying AEs at baseline and during treatment is informative . MinD was not responsive to either a conventional antidepressant or a nutraceutical , and both compounds were associated with a notable side effects burden . Other treatment approaches for MinD should be investigated Major Depressive Disorder ( MDD ) is a common illness that affects > 40 million people worldwide , and antidepressants are one of the top 5 leading classes of pharmaceuticals with annual sales in excess of $ 20 billion ( 1,2 ) . The current st and ard of care focuses on serotonin−norepinephrine reuptake inhibitors ( SNRI ) and selective serotonin reuptake inhibitors ( SSRI ) ; however , patients often respond poorly . In fact , the National Institute of Mental Health conducted a large-scale STAR*D study and found that 63 % of patients did not achieve remission with the SSRI Citalopram ( 1,3−5 ) . Citalopram was originally developed in Lundbeck in the late 1980s and sold as a racemate . Lundbeck , in collaboration with Forest Laboratories , has recently released an up date d version called Escitalopram ( also known as Lexapro ) , which is the single (S)-enantiomer of the racemic Citalopram , which provided new patent life . In 2009 , Lexapro garnered ∼$2.7 billion in sales in the US ( Figure ​(Figure1)1 ) ( 2 ) . Figure 1 Structures of Citalopram , Escitalopram , and TC-5214 . An alternative hypothesis for depression emerged over 30 years ago and suggests that a cholinergic imbalance ( hypercholinergic tone ) is a major factor in depression , and both clinical and pre clinical studies have implicated neuronal nicotinic cholinergic receptors ( NNRs ) rather than muscarinic receptors ( 5 ) . On the basis of these data , AstraZeneca and Targacept have explored the role of NNR antagonism in depressive disorders and recently announced the initiation of a phase III trial of TC-5214 , (S)-(+)-mecamylamine , as an adjunct therapy with Citalopram . TC-5214 is a low molecular weight ( 167.3 as free base , 203.8 as the HCl salt ) , basic ( pKa = 11.5 ) compound , freely soluble in water . While TC-5214 displays modest selectivity among the NNRs , its antidepressive properties are presumed to be the result of inhibition of the α4β2 NNRs . Pre clinical ly , TC-5214 demonstrated robust efficacy in rodent models of depression ( forced swim and behavioral despair ) and anxiety ( social interaction and light/dark chamber ) . The (S)-enantiomer showed a superior preclincial safety profile compared to that of either the racemic compound or the (R)-enantiomer . Furthermore , TC-5214 was well tolerated in both acute and chronic toxicity tests , displayed no mutagenic potential , and possessed pharmacokinetic properties suitable for development ( 3−5 ) . In 2009 , Targacept conducted a double blind , placebo controlled phase IIb trial in MMD patients with TC-5214  , as an adjunct treatment with Citalopram demonstrated superiority to placebo in both primary and secondary outcome measures ( 3−5 ) . This positive outcome led to a license agreement in December of 2009 with AstraZeneca for the global development and commercialization of TC-5214 . On June 23 , 2010 , AstraZeneca and Targacept announced the enrollment of the first patients in the phase III trial of TC-4214 . Coined the Renaissance Program , the trial will include two fixed dose and two flexible dose phase III studies of TC-5214 as an adjunct treatment for patients with poor response to st and ard SSRI or SNRI therapy . Each fixed dose and flexible dose phase III study will employ an initial open label phase wherein patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to assess therapeutic response . Patients that respond poorly will then be r and omized into a double blind , placebo controlled second phase to receive a fixed or a flexible dose of TC-5214 or placebo , twice daily , while continuing the SSRI or SNRI therapy . A change from double blind baseline for TC-5214 on the Montgomery−Asberg Depression Rating Scale ( MADRS ) as compared to placebo is the primary outcome measure . The program will also include a double blind , placebo controlled study for long-term safety . The companies plan completion of the trial in time to file an IND with the FDA in late 2012 ( 3−5 ) . MMD is the leading cause of disability in the US for people 15−44 , and the burden for MDD in the US in 2000 was in excess of $ 83 billion ( 6 ) . When broken down , the workplace burden for lost time is ∼62 % , treatment costs account for ∼31 % , and suicide related costs average 7 % ( 6 ) . For those suffering from MDD with poor response to SSRIs and SNRIs , the phase III data is anxiously awaited CONTEXT Little is known about selecting among second-step medications for major depressive disorder after intolerance or lack of remission with an initial selective serotonin reuptake inhibitor . OBJECTIVE To determine whether sociodemographic , clinical , or first-step treatment features predict remission with or intolerance overall or differentially to any 1 of 3 second-step medications after an unsatisfactory outcome with citalopram hydrobromide . DESIGN An equipoise stratified r and omized study . Participants were recruited from July 17 , 2001 , through April 20 , 2004 . SETTING Public or private sector primary care ( n = 18 ) and psychiatric care ( n = 23 ) setting s across the United States . PARTICIPANTS Representative out patients aged 18 to 75 years with nonpsychotic major depressive disorder ( N = 727 ) . INTERVENTIONS Sustained-release bupropion hydrochloride was started at 150 mg/d and incrementally increased to 400 mg/d . Sertraline hydrochloride was started at 50 mg/d and incrementally increased to 200 mg/d . Extended-release venlafaxine hydrochloride was started at 37.5 mg/d and incrementally increased to 375 mg/d . MAIN OUTCOME MEASURES The 16-item Quick Inventory of Depressive Symptomatology , Self-Rated and the Frequency , Intensity , and Burden of Side Effects Rating . RESULTS Remission was more likely among participants who were white , employed , cohabiting or married , or privately insured or who had prior intolerance to citalopram or at least a response to citalopram , and no prior suicide attempts . Remission was less likely among participants with concurrent generalized anxiety , obsessive-compulsive , panic , or posttraumatic stress disorders ; social phobia ; anxious or melancholic features ; or more severe depression . Intolerance was less likely for Hispanic participants , but more likely for participants with previous suicide attempts or intolerance to citalopram . Participants with concurrent substance use were less likely to remit ( odds ratio , 0.37 ) and more likely not to tolerate extended-release venlafaxine . Intolerance to citalopram was associated with intolerance to sertraline ( P = .04 ) . CONCLUSIONS Clinical , demographic , and treatment history were of little value in recommending 1 medication vs another as a second-step treatment for major depressive disorder . Participants most likely to remit in the second step had less Axis I psychiatric disorder comorbidity , less social disadvantage , and at least a response to citalopram in the first step . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00021528 Background : Interferon-induced depression represents a major complication in antiviral treatment of chronic hepatitis C virus ( HCV ) infection . Aim : To evaluate in a placebo-controlled study the efficacy of a selective serotonin reuptake inhibitor ( SSRI ) in HCV patients on antiviral therapy with interferon-associated depression . Methods : 100 HCV out patients were included in a r and omised , double-blind , placebo-controlled study . During interferon therapy ( peginterferon alfa-2b plus ribavirin ) , depression was monitored using the Hospital Anxiety and Depression Scale ( HADS ) .  Patients with clinical ly relevant interferon-induced depression ( HADS ⩾9 ) were r and omly assigned to placebo or citalopram ( SSRI , 20 mg/day ) . Results : In 28 patients ( 28 % ) , HADS scores increased to > 8 during interferon therapy . They were treated with placebo ( n = 14 ) or SSRI ( n = 14 ) . HADS scores declined significantly in SSRI patients within four weeks of therapy ( p<0.001 ) but not in placebo patients . This difference between subgroups was statistically significant ( p = 0.032 ) . Unblinding became necessary in five placebo patients as a result of intolerable depression . Rescue medication ( 20 mg citalopram ) led to a significant decrease in HADS scores ( p = 0.008 ) . All citalopram patients were able to complete interferon therapy as planned . As an interim analysis showed a significant superiority of SSRI over placebo , the study was terminated prematurely . Three patients , who became depressed afterwards , were treated in an unblinded fashion with citalopram . Conclusions : The findings demonstrate clearly that citalopram treatment is highly effective in HCV patients on interferon therapy , when initiated after the onset of clinical ly relevant depressive symptoms . This suggests that a general SSRI prophylaxis is not necessary in these patients Objective : This study assessed the efficacy , safety , and tolerability of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine and the selective serotonin reuptake inhibitor escitalopram for major depressive disorder ( MDD ) in postmenopausal women . Methods : In this r and omized , double-blind study , postmenopausal out patients ( aged 40 - 70 y ) with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition MDD received flexible-dose desvenlafaxine ( 100 - 200 mg/d ) or escitalopram ( 10 - 20 mg/d ) for 8 weeks . Acute-phase responders , that is , women with a 50 % or greater reduction from baseline in the 17-item Hamilton Rating Scale for Depression ( HAM-D17 ) total score , were eligible to continue the same double-blind treatment in the 6-month continuation phase . The primary efficacy outcomes were mean change from baseline in HAM-D17 total score ( acute phase ) , analyzed using a mixed-effects model for repeated measures , and the proportion of women who maintained response ( continuation phase ) , analyzed using logistic regression . Results : Reductions in HAM-D17 total score at acute-phase endpoint were similar for desvenlafaxine- and escitalopram-treated women ( −13.6 vs −14.3 , respectively ; P = 0.24 ) . No significant difference was observed between groups at continuation-phase endpoint in the proportion of women who maintained response ( desvenlafaxine , 82 % ; escitalopram , 80 % ; P = 0.70 ) . In both phases , desvenlafaxine and escitalopram  were generally safe and well tolerated . Conclusions : Among postmenopausal out patients with MDD , there were no significant differences in the efficacy of desvenlafaxine and escitalopram based on primary efficacy analyses . The results do not support the overall hypothesis that the serotonin-norepinephrine reuptake inhibitor desvenlafaxine has an efficacy advantage for the treatment of MDD in postmenopausal women because , in this particular subgroup , desvenlafaxine failed to prove superiority over escitalopram  . Safety and tolerability were comparable Objective : We have tested the relapse‐preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder ( SAD ) responding to 1 week of light therapy In r and omised controlled trials ( RCTs ) there are two types of validity : internal validity and external validity . Internal validity refers to the extent to which the observed difference between groups can be correctly attributed to the intervention under investigation . In other words , it is the extent to which the design and conduct of the trial eliminate error . Internal validity might be threatened by two types of errors : systematic error ( also called bias ) and chance error ( also called r and om error or statistical error ) ( Keirse & Hanssens , 2000 . Systematic error , or bias , may be the consequence of erroneous ways of collecting , analysing and interpreting data . This may produce differences between treatments that are not real , with an overestimation or an underestimation of the true beneficial or harmful effect of an intervention ( Juni et al. , 2001 ) . In RCTs there are four types of bias : selection bias ( when the groups differ in baseline characteristics because of the way participants are selected ) , performance bias ( when the care provided to the trial participants differs systematic ally between the experimental and control group ) , detection bias ( when there are systematic differences in outcome assessment ) , and attrition bias ( when the loss of participants from the study systematic ally differs between the experimental and control group ) . By contrast , chance error , or statistical error , is due to outcome variability that may arise by chance alone . Studies with small sample sizes are more likely to incur in this type of error than studies with large sample sizes . Thus , the risk of r and om error may be minimised by recruiting sufficiently large sample s of patients Citalopram is a bicyclic phtalane derivative . In animal experiments , citalopram has been demonstrated to possess a potent and highly selective inhibitory effect on serotonin reuptake . Several studies in man have indicated that citalopram given in daily doses of 40–60 mg has antidepressant properties and few side effects . The present double-blind study investigated the effects of three doses of citalopram ( 5 mg , 25 mg , and 50 mg ) on depressive symptoms and various biochemical variables in 26 depressive patients . A significant reduction of the clinical ratings of depressive symptoms occurred at all dose levels . In endogenously depressed patients , a dose of 25 or 50 mg daily seemed to have the most pronounced antidepressive effect . The side effects were few and not related to dose level . A highly significant decrease in 5-HIAA in the CSF was found . MOPEG in the CSF was also significantly decreased , while HVA in the CSF was increased . In addition , a significant decrease in the plasma concentrations of valine , leucine , tyrosine , and histidine was found . None of the biochemical effects was dose-dependent . The complex pattern of biochemical effects indicate that the amelioration of depressive symptoms might be related to effects of citalopram on central monoaminergic mechanisms and peripheral amino acid concentrations In making treatment decisions , doctors and patients must take into account relevant r and omised controlled trials ( RCTs ) and systematic review s. Relevance depends on external validity ( or generalisability)--ie , whether the results can be reasonably applied to a definable group of patients in a particular clinical setting in routine practice . There is concern among clinicians that external validity is often poor , particularly for some pharmaceutical industry trials , a perception that has led to underuse of treatments that are effective . Yet research ers , funding agencies , ethics committees , the pharmaceutical industry , medical journals , and governmental regulators alike all neglect external validity , leaving clinicians to make judgments . However , reporting of the determinants of external validity in trial publications and systematic review s is usually inadequate . This review discusses those determinants , presents a checklist for clinicians , and makes recommendations for greater consideration of external validity in the design and reporting of RCTs BACKGROUND This study compares antidepressant efficacy and tolerability of citalopram given either orally or as a slow drop infusion . METHODS Citalopram ( 40 mg/day ) was administered double-blindly as tablets or slow-drop infusion during the first 10 days and then open , orally , up to treatment Day 42 . RESULTS In 60 moderately to severely depressed patients , the Hamilton depression total score ( 17-items ) at baseline was 23.9 and 23.6 in the active infusion ( n = 30 ) and active tablet ( n = 30 ) group , respectively . These scores dropped in both groups to 15.6 and 16.9 on Day 10 , and to 10.3 and 10.2 on Day 42 . Response rates ( delta Hamilton > or = 50 % ) amounted to 33.3 % and 17.9 % on Day 10 , and 66.2 % and 63.3 % on Day 42 , without a relevant group difference in citalopram plasma concentration . CONCLUSION Slow-drop infusion with citalopram shows a similar risk/benefit relationship to oral citalopram . The design of this study allowed us to evaluate pharmacological but not psychological factors which may contribute to response to slow-drop infusion Escitalopram is the S-enantiomer of citalopram . In this study , we compared the efficacy of equivalent dosages of escitalopram and citalopram in the treatment of moderate to severe major depressive disorder ( MDD ) , based on data from two , pooled , r and omized , double-blind , placebo-controlled studies of escitalopram  in which citalopram was the active reference . The primary efficacy parameter was the mean change from baseline in the Montgomery Åsberg Depression Rating Scale ( MADRS ) total score . Significant differences in favour of escitalopram were observed for the MADRS [ P<0.05 , observed cases (OC)/last observation carried forward ( LOCF ) ] and Clinical Global Improvement – Severity of Illness scores ( CGI-S ; P<0.05 , OC/LOCF ) . Escitalopram separated from placebo at week 1 on the primary efficacy parameter , whereas citalopram first separated from placebo at week 6 . An analysis of time to response showed that escitalopram-treated patients responded significantly faster to treatment than citalopram-treated patients ( P<0.01 ) . More patients responded to and achieved remission with escitalopram than to citalopram ( P<0.05 , OC ) . The HAMD scale was only used in the fixed-dose study , where escitalopram-treated patients had a significant reduction in HAMD-17 total score at week 8 compared to citalopram-treated patients ( P<0.05 , OC/LOCF ) . In the pooled sub population of severely ill patients ( MADRS≥30 )  , escitalopram-treated patients showed greater improvement than citalopram-treated patients ( P<0.05 , LOCF/OC ) . Escitalopram showed consistently superior efficacy compared to citalopram in the treatment of moderate to severe MDD on all efficacy parameters , and was similarly well tolerated OBJECTIVE Predictors of treatment response to serotonergic versus nonserotonergic , e.g. , noradrenergic , antidepressants are of considerable clinical relevance as they could help to reduce the occurrence of patients ' receiving weeks or even months of unsuccessful treatment . Several studies show that the response to selective serotonin reuptake inhibitors can be successfully predicted by using the loudness dependence of auditory evoked potentials ( LDAEP ) , which denotes change in the amplitudes in response to different stimulus intensities and is to date one of the best vali date d indicators of the central serotonergic system . The aim of the current r and omized prospect i ve study was to investigate whether or not LDAEP also allows the differential prediction of treatment response to serotonergic versus noradrenergic antidepressants . METHOD Electrophysiologic recordings were performed on 48 subjects between 1999 and 2001 . After exclusions due to artifacts , the study sample consisted of 35 unmedicated in patients with a DSM-IV or ICD-10 diagnosis of major depressive disorder ( mean + /- SD age = 42.5 + /- 10.8 years ; 13 male , 22 female ; mean + /- SD score of 28.9 + /- 5.7 on the Hamilton Rating Scale for Depression [ HAM-D ] , the primary measure for psychopathology ) . The patients were then treated for 4 weeks with either the selective serotonin reuptake inhibitor citalopram or the noradrenaline reuptake inhibitor reboxetine . RESULTS Analysis of variance ( F = 5.05 , df = 1,31 ; p = .03 ) revealed that responders ( 50 % improvement in HAM-D score ) to the citalopram treatment were characterized by a strong LDAEP at baseline , and responders to reboxetine were characterized by a weak LDAEP at baseline . Non-responders to citalopram or reboxetine showed the inverse LDAEP characteristics , respectively . CONCLUSION This study is one of the first to demonstrate differential prediction of response to different classes of antidepressants . Patients at the beginning of an antidepressant treatment who show an initially strong LDAEP have a greater probability of responding to a serotonin-agonist antidepressant , whereas patients with a weak LDAEP will probably benefit more from a nonserotonergic , e.g. , noradrenergic , antidepressant . If these results were replicated in a larger sample , this simple electroencephalographic method could be more broadly used in clinical practice to support clinicians in replacing the trial and error method with a more targeted and individualized approach to antidepressant treatment This study sought to investigate the efficacy of escitalopram at different dosages for the treatment of obsessive – compulsive disorder ( OCD ) . Thirty individuals were enrolled in a 16-week , open-label trial of escitalopram  and r and omly assigned to the 20 or 30 mg study arm . Study measures assessing OCD symptoms , anxiety , depression , and quality of life were administered at baseline and weeks 2 , 4 , 8 , 12 , and 16 . For the 23 study completers , pretreatment and posttreatment analyses revealed significant improvements ( P<0.05 ) on clinician-rated and self-rated measures of OCD symptoms , quality of life , anxiety , and depression . Approximately half of the sample ( n = 12 ) satisfied full medication response criteria and less than one-quarter ( n = 5 ) were partial medication responders . Intention-to-treat analyses showed similar improvements ( P<0.05 ) on all study measures . At study completion , a superior responder rate and more improvement on the Yale – Brown Obsessive Compulsive Scale ( P<0.05 ) was reported for those in the 30 versus 20 mg study arm . The difference between the two groups , however , disappeared when initial differences in baseline depression and anxiety scores were used as analysis covariates . These results suggest that the 30 mg ( vs. 20 mg ) dose of escitalopram may provide a superior reduction in OCD symptoms for those sufferers with comorbid depression and /or anxiety The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants ( TCAs ) , and the frequency and type of adverse events , have made the treatment of depression in this group difficult . The selective serotonin reuptake inhibitors ( SSRIs ) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs . We compared the therapeutic actions and side effects produced by citalopram , the most selective SSRI available , with amitriptyline in a group of elderly patients ( aged 65 and older ) diagnosed with major depression . In a double-blind , double-dummy , parallel-group , multicenter comparison of citalopram ( 20 or 40 mg/day ) and amitriptyline ( 50 or 100 mg/day ) , patients who did not respond to placebo during a 1-week single-blind phase were r and omly assigned to receive citalopram or amitriptyline for 8 weeks . Efficacy measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Depression Scale ( HAMD ) , and Clinical Global Impressions . Both drug treatments produced equivalent time-related declines in severity of depression , so that by 8 weeks slightly more than 50 % of the patients in each group experienced marked recovery , defined as MADRS scores < or = 12 . Amitriptyline produced a greater overall incidence of adverse events , including a significantly higher ( P < 0.001 ) percentage of patients reporting dry mouth ( 34 % vs. 7 % ) , as well as a significantly higher ( P < 0.02 ) incidence of somnolence . Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group . For only one event ( nausea ) did the citalopram group report a significantly greater ( P = 0.012 ) incidence ( 12.8 % vs. 4.8 % ) . On the basis of these results , it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly . Because of its low incidence and low magnitude of side effects , citalopram seems especially useful in private practice Although serotonin reuptake inhibitors ( SRIs ) are the medications of choice in the treatment of obsessive-compulsive disorder ( OCD ) , only 50 - 60 % of patients respond to a single trial of any of these agents . Improved knowledge of the predictors of response to treatment may have important clinical implication s. Data from a large r and omized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response . Demographic ( age , sex ) , clinical ( OCD severity and duration , depression severity , prior treatment ) and trial variables  ( citalopram dose , treatment duration ) were included . Subjects with longer duration of OCD , more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial . In contrast , subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders . Despite greater awareness of OCD in recent years , there is evidence that the disorder continues to be underdiagnosed and undertreated . The data here emphasize the crucial importance of early diagnosis and treatment of OCD , and of pharmacotherapy with appropriate dose and duration BACKGROUND Timely administration/supplementation of a specific serotonin reuptake inhibitor with a second therapeutic agent could improve treatment outcome in patients with major depressive disorder ( MDD ) . The purpose of this study was to identify the optimal time at which to implement supplementation so as to maximize the likelihood of remission by 8 weeks and minimize overtreatment . METHOD Data from patients with MDD treated with sertraline ( n = 108 ) or citalopram ( n = 107 ) in a r and omized controlled trial were analyzed by multivariate logistic regression . The 21-item Hamilton Depression Scale scores at weeks 1 , 2 , 3 , 4 , and 6 ; sex ; age ; and baseline Hamilton Anxiety Scale score were used as predictors of remission by 8 weeks sustained for a further 4 weeks . RESULTS Regression models for weeks 2 , 3 , 4 , and 6 were significant ( area under the curve values , 0.73 - 0.91 ) . The models for weeks 3 to 6 yielded κ coefficients greater than 0.40 with the outcome variable . A Hamilton Depression Scale reduction score of 50 % at week 4 as a criterion for supplementation would have result ed in overtreatment of 4 % and 0 % of patients in the sertraline and citalopram groups , respectively , and none if applied at week 6 . The rates at which patients who should have received supplementation ( destined to be nonremitters at 8 weeks ) would have been missed would be 49%/54 % for sertraline/citalopram at week 4 and 43%/50 % at week 6 . LIMITATIONS The study limitations are as follows : secondary analysis of data , relatively low sertraline dose , and relatively small sample sizes . CONCLUSIONS It may be possible to identify patients treated with specific serotonin reuptake inhibitors  who will not achieve sustained remission by 8 weeks . If supplementation were implemented accordingly , the number of overtreated patients would be small . However , a substantial number of patients who should be supplemented would be missed , indicating a need for greater sensitivity of the prediction model . Further studies are needed BACKGROUND The S-enantiomer of citalopram ( escitalopram ) is the active moiety linked to the anti-depressant effects associated with citalopram ( the racemate ) . For escitalopram to be approved for the treatment of depression in Europe , findings from clinical trials of escitalopram are required to match previous results from studies of the racemate , citalopram . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of escitalopram and citalopram in out patients with major depressive disorder ( MDD ) . METHODS This prospect i ve , r and omized , double-blind , active-controlled study was conducted at 8 psychiatric outpatient clinics in the Federation of Russia . Adult out patients aged 25 to 45 years with MDD and a total score > or = 25 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were eligible . Patients were r and omly assigned to receive 6 weeks of treatment with fixed daily doses of escitalopram 10 mg , citalopram 10 mg , or citalopram 20 mg . Efficacy assessment s were made at weeks 0 ( baseline ) , 1 , 4 , and 6 ( study end or last observation carried forward ) . The primary efficacy parameter was the change from baseline in MADRS total score . Secondary measures were the change from baseline in MADRS total score in a subgroup of severely depressed patients ( baseline MADRS total score , > or = 35 ) , MADRS core depression subscale score , and Clinical Global Impression-Severity and Improvement ( CGI-S and CGI-I ) scores ; and the proportions of patients classified as responders and remitters at study end . Tolerability was assessed using adverse events ( AEs ) recorded by the investigator . RESULTS Of 330 assessable r and omized patients , 8 withdrew , including 7 who withdrew consent and 1 who withdrew due to recurrence of a preexisting event . Thus , 322 patients were included in the assessment ( mean age , 35 years ; 41.6 % male ; all white ;  escitalopram 10 mg , 108 patients ; citalopram 10 mg , 106 ; citalopram 20 mg , 108 ) . At study end , the mean ( SE ) change from baseline in MADRS total score was significantly greater in the escitalopram arm than in the 10- and 20-rag citalopram arms ( -28.70 [ 0.78 ] vs -20.11 [ 0.80 ] and -25.19 [ 0.78 ] ; both , P < 0.001 ) . Improvements were more marked in the severely depressed subgroup ( -30.33 [ 0.95 ] vs -20.87 [ 0.99 ] and -26.34 [ 0.91 ] ) . Changes in the CGI-S and CGI-I scores and the rates of response and remission were significantly greater in the escitalopram group compared with those in the citalopram 10- and 20-mg groups ( CGI-S : -2.60 [ 0.10 ] vs -1.61 [ 0.10 ] and -2.05 [ 0.10 ] ; CGI-I : + 1.58 [ 0.09 ] vs + 2.35 [ 0.10 ] and + 1.80 [ 0.09 ] ; response : 95.4 % vs 44.3 % and 83.3 % ; remission : 89.8 % vs 25.5 % and 50.9 % [ all , P < 0.001 ] ) . Mean ( SE ) changes from baseline in core depression subscale score were -19.00 ( 0.59 ) , -13.00 ( 0.60 ) , and -16.52 ( 0.58 ) with escitalopram , citalopram 10 mg , and citalopram 20 mg , respectively . The prevalence of AEs was significantly lower in the escitalopram group ( 7 ) compared with the citalopram groups ( 16 and 19 in the 10- and 20-mg groups , respectively ; both , P < 0.05 ) . Nausea ( 2 [ 1.9 % ] , 5 [ 4.7 % ] , and 7 [ 6.5 % ] patients in the escitalopram and citalopram 10- and 20-mg groups , respectively ) and headache ( 1 [ 0.9 % ] , 2 [ 1.9 % ] , and 4 [ 3.7 % ] ) were the most frequently reported AEs . CONCLUSIONS The results from this study suggest that escitalopram 10 mg was more effective than citalopram 10 and 20 mg at 6 weeks in these adult out patients with MDD . All treatments were well tolerated ABSTRACT – In a double‐blind trial , comprising 60 endogenously depressed patients , citalopram was compared with mianserin .  Fifty‐eight patients completed the 6‐week trial period with ratings and side effect recordings at weeks 0 , 1 , 2 , 4 , and 6 . Both drugs were administered as a single evening dose , 20–80 mg ( most frequently 40 mg ) for citalopram and 60–120 mg ( most frequently 90 mg ) for mianserin . CPRS ( Subscale for Depression ) total scores showed a highly significant reduction in both groups with a significant difference in favour of citalopram after 1 and 2 weeks . Based on the Global Evaluation of the Severity of Illness there were 18 complete and three partial responders on citalopram and 13 complete and four partial responders on mianserin . Six patients on citalopram and one patient on mianserin  showed mild or moderate side effects , but no cardiovascular side effects were recorded . The authors conclude that citalopram is a safe antidepressant drug , presumably better than mianserin & NA ; The abrupt discontinuation of antidepressants can result in a syndrome of adverse events , including somatic , mood and psychomotor reactions . This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors ( SSRIs ) on cognitive and psychomotor function . Eighty‐seven patients receiving maintenance therapy with fluoxetine , sertraline , paroxetine or citalopram had their treatment interrupted for 4‐7 days using double‐blind placebo . Assessment s of aspects of cognitive and psychomotor performance , mood and symptoms were carried out at each visit . Following interruption of treatment , significant differences between the groups emerged . Paroxetine treated patients experienced significantly more cognitive failures ( P = 0.007 ) , poorer quality of sleep ( P = 0.016 ) , and an increase in depressive symptoms , as rated both subjectively , using the Zung scale ( P = 0.006 ) and by the clinician , using the Montgomery‐Asberg Depression Rating Scale ( P = 0.0003 ) and Clinical Global Impression ( P = 0.0003 ) , compared to some or all of the other drugs . All changes were reversed on reinstatement of treatment . Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning , which may be related to the antidepressant discontinuation syndrome . These effects are not evident in patients receiving fluoxetine , sertraline and citalopram , suggesting they are not an SSRI class phenomenon . Int Clin Psychopharmacol 15:305‐318 © 2000 Lippincott Williams & Post-hoc pooled analysis of data from two 6-month r and omised controlled trials in patients with major depressive disorder ( MDD ) revealed superior efficacy and tolerability of escitalopram when compared with paroxetine . Escitalopram ( n=394 ) produced a significantly ( p<0.01 ) greater mean treatment difference of 2.0 points in primary endpoints , judged using the Montgomery-Asberg Depression Rating Scale ( MADRS ) total score , compared with paroxetine ( n=383 ) . Significant differences were also observed in Clinical Global Impression (CGI)--severity  ( escitalopram , 2.1 ; paroxetine , 2.4 ; p<0.01 ) and CGI -- improvement ( escitalopram , 1.8 ; paroxetine , 2.0 : p<0.01 ) . In the sub-group of severely depressed patients ( baseline MADRS > or = 30 ) , escitalopram showed further improved efficacy compared with paroxetine in all scores . This analysis supports previous observations of superior efficacy and tolerability of long-term escitalopram treatment ( 10 to 20 mg/day ) compared with paroxetine ( 20 to 40 mg/day ) . Escitalopram is a good therapeutic option for the long-term treatment of MDD , particularly in severely depressed patients Abstract Aim : To assess the relative cost effectiveness of escitalopram compared with venlafaxine XR in patients with major depressive disorder ( MDD ) . Methods : An economic evaluation was conducted alongside a double-blind , multinational , r and omised clinical trial and examined the costs and quality of life of 251 patients taking escitalopram versus venlafaxine . Out patients fulfilling criteria for MDD were r and omised to receive oral escitalopram 10–20 mg/day or venlafaxine 75–150 mg/day for 8 weeks . Patient-reported outcomes ( EuroQOL question naire , Quality of Life Depression Scale ) , use of medical services and absence from work ( relating to the previous 3 months ) were recorded at baseline , with repeated measurements at week 8 . Unit costs in year values were applied to the re source utilisation data . A cost-effectiveness analysis was performed using the EuroQOL score as the effectiveness measure . The perspective was that of the healthcare payer , with a societal perspective considered in a sensitivity analysis . Results : Statistically significant improvements in patient-reported outcomes ( vs baseline ) were observed in both groups after 8 weeks ’ treatment . Patients treated with escitalopram tended to report fewer problems on the EuroQOL dimensions than venlafaxine recipients . Mean per-patient costs in euros ( € , year 2003 values ) for the escitalopram group , compared with the venlafaxine group , were 32 % lower ( € 110 vs € 161 ) from a healthcare perspective , although this was not a statistically significant difference . Differences were related to lower drug acquisition costs and fewer hospitalisations  for escitalopram than venlafaxine recipients . A multivariate model adjusting for baseline characteristics showed that escitalopram  reduced direct costs compared with venlafaxine ( p = 0.007 ) . Bootstrapped distributions of the incremental cost-effectiveness ratios also showed similar effectiveness but lower costs for escitalopram compared with venlafaxine . Inclusion of indirect costs led to similar results . Conclusion : This prospect i ve economic analysis suggests that escitalopram has similar effectiveness to venlafaxine in the treatment of MDD , but may be associated with lower healthcare costs . These findings are consistent with previously published economic evaluations We aim ed to compare the antidepressant and anxiolytic effects , tolerability and effects on quality of life of mirtazapine and citalopram in a r and omized , double-blind , multicentre , 8-week study . Patients with a Major Depressive Episode ( DSM-IV ) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were r and omized to 8 weeks treatment with either mirtazapine  ( n = 137 , 15 - 60 mg/day ) or citalopram ( n = 133 , 20 - 60 mg/day ) . Efficacy was evaluated by the MADRS , Hamilton Anxiety Scale ( HAM-A ) , Clinical Global Impression scales ( CGI ) , the Leeds Sleep Evaluation Question naire ( LSEQ ) and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method . Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit . The magnitude of reduction from baseline in group mean MADRS scores was large in both groups , reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group . Both treatments also result ed in a substantial improvement in anxiety symptoms , sleep disturbances and quality of life , and high percentage of responders . However , at day 14 , statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS , HAM-A and CGI-Severity of illness and Quality of life scores . A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinical ly relevant superiority between two proven antidepressants . Mirtazapine treatment was also related to faster improvement of sleep , quality of sleep and improved alertness following awakening , as shown by statistically significant differences on the self-rating LSEQ at various time points . There were no differences between two treatment groups on self-rating QLSEQ . Both drugs were well tolerated , with a low number of patients in either group prematurely terminating the study due to adverse events  ( mirtazapine : 3.6 % , citalopram , 3.0 % ) . Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group . There were no clinical ly relevant changes in laboratory parameters and vital sign variables with either treatment , except for clinical ly relevant increase in body weight , occurring more frequently in mirtazapine patients . In this study , mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety , and well tolerated . However , mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS , HAM-A and CGI Severity of illness and Quality of life scales . This finding , consistently present at all major efficacy variables , suggests potentially faster onset of efficacy of mirtazapine over citalopram BACKGROUND This r and omized , open-label , rater-blinded , multicenter study compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine extended release ( ER ) with selective serotonin reuptake inhibitors ( SSRIs ) in primary care patients with major depressive disorder . METHOD Study data were collected from November 29 , 2000 , to March 4 , 2003 . Out patients who met diagnostic criteria for major depressive disorder according to the Mental Health Screener , a computer-administered telephone interview program that screens for the most common mental disorders , and had a total score on the 17-item Hamilton Depression Rating Scale ( HDRS(17 ) ) ≥ 20 were r and omly assigned to receive up to 6 months of open-label venlafaxine ER 75 - 225 mg/d ( n = 688 ) or an SSRI ( n = 697 ) : fluoxetine 20 - 80 mg/d , paroxetine 20 - 50 mg/d , citalopram 20 - 40 mg/d , and sertraline 50 - 200 mg/d . The primary outcome was remission ( HDRS(17 ) score ≤ 7 ) at study end point using the last-observation-carried-forward method to account for early termination . A mixed-effects model for repeated measures ( MMRM ) analysis evaluated secondary outcome measures . RESULTS Fifty-one percent of patients completed the study . Month 6 remission rates did not differ significantly for venlafaxine ER and the SSRIs ( 35.5 % vs 32.0 % , respectively ; P = .195 ) . The MMRM analysis of HDRS(17 ) scores also did not differ significantly ( P = .0538 ) . Significant treatment effects favoring the venlafaxine ER group were observed for remission rates at days 30 , 60 , 90 , and 135 and a survival analysis of time to remission ( P = .006 ) , as well as Clinical Global Impressions-severity of illness scale ( P = .0002 ) ; Hospital Anxiety and Depression Scale-Anxiety subscale ( P = .03 ) ; 6-item Hamilton Depression Rating Scale , Bech version ( P = .009 ) ; and Quick Inventory of Depressive Symptomatology-Self-Report ( P = .0003 ) . CONCLUSIONS Remission rates for patients treated with venlafaxine ER or an SSRI did not differ significantly after 6 months of treatment . Results of most secondary analyses suggested that SNRI treatment had a greater antidepressant effect versus the SSRIs studied Depression is the most common psychiatric disorder among the elderly and in old age may interact with emotional and cognitive functioning . Depression in old age has been shown to be associated with degenerative changes in the brain . It is , therefore , important that in this patient population antidepressants with a favourable tolerability profile , such as the selective serotonin reuptake inhibitors ( SSRIs ) , are examined for both antidepressant efficacy and effect on cognitive function and emotional impairment . This r and omised , double-blind study compared the efficacy and tolerability of citalopram and mianserin in 336 elderly , depressed patients with or without dementia . Patients received either citalopram 20 - 40 mg/day or mianserin 30 - 60 mg/day for 12 weeks . The treatments were equivalent with respect to change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score ; patients in both treatment groups responded well . Patients with dementia showed a smaller decrease in total MADRS score than patients without dementia . Both treatments were well tolerated with a relatively low incidence of adverse events . Fatigue and somnolence were more frequent with mianserin , while insomnia was more frequent with citalopram . Overall , this study showed that the two treatments were equivalent in efficacy , and that citalopram is an effective , well-tolerated and non-sedative treatment for elderly depressed patients with or without dementia Alzheimer 's disease is the most frequent form of dementia , where behavioral and cognitive disruption symptoms coexist . Depression , apathy , anxiety , and other conduct disorders are the complaints most often reported by caregivers . Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer 's disease . Cognitive impairment was equally distributed among the subjects . Patients , aged 68 to 76 years old , were r and omized to receive inhibitors of cholinesterase ( Donepezil , 5 mg/ day ) alone , or inhibitors of cholinesterase plus selective seratonin reuptake inhibitors ( SSRIs ) ( citalopram HBr , 20 mg/day ) . We followed up all the patients for one year , with particular concern for neuropsychological aspects associated with eventual behavioral changes . Results indicate that SSRI intake seems to be effective for depression , decreasing it and improving quality of life for both patients and caregivers . Side effects in both groups were few , and there were no study withdrawals . This paper discusses the relationship between dementia- and depression , and presents our finding that depressive symptoms , if specifically treated , tend to reduce caregiver stress and improve well-being in patients with Alzheimer 's disease Milnacipran is a new antidepressant with similar effects on the reuptake of noradrenaline and serotonin in vivo and in vitro . The present study was design ed to study the efficary and tolerability of long-term treatment of depressed patients with milnacipran in comparison with clomipramine . The study was design ed as a double-blind , r and omized parallel group comparison at 10 different hospitals in The Netherl and s. The duration of treatment was 6 weeks , with an extension period of 20 weeks . The entire study period of 26 weeks was done under double-blind conditions . There was 1 week of dose escalation after which the patients received either treatment with milnacipran 200 mg/day or clomipramine 150 mg/day in fixed doses during weeks 2 to 10 . This was followed by flexible dosing with 200 , 150 , or 100 mg/day milnacipran or 150 , 100 or 75 mg/day clomipramine during weeks 11 to 26 . Both milnacipran and clomipramine showed poor antidepressant activity in this patient sample . There were no significant differences between the two treatment groups with respect to antidepressant efficacy . Several method ological reasons might explain the lack of antidepressant efficacy in the present study . In 45 % of the patients in the present study , the duration of the current episode of depression was longer than 6 months , whereas 48 % of the patients used antidepressants before the study and 73 % of these appeared to be non-responders . This raises the possibility that the present sample consisted of treatment-resistant depressive patients OBJECTIVE Citalopram and sertraline are widely prescribed selective serotonin reuptake inhibitors ( SSRIs ) . There is no conclusive evidence to show superiority of citalopram or sertraline in terms of efficacy or tolerability . Hence this study was design ed to compare short term efficacy and safety of citalopram and sertraline in major depressive disorder ( MDD ) in Indian patients . METHODS In an open , r and omized study , 100 patients were divided into two groups . In Group A ( n = 50 ) patients received citalopram ( 20 - 60 mg/day ) for 6 weeks . In Group B ( n = 50 ) patients received sertraline ( 50 - 150 mg/day ) for 6 weeks . Patients were evaluated at baseline and then at 1 , 2 , 3 , 4 , 5 , and 6 weeks . RESULTS There was significant improvement in Hamilton depression rating scale ( HDRS ) , Montgomery and Asberg depression rating scale ( MADRS ) and Amritsar depressive inventory ( ADI ) scores ( p < 0.05 ) with both the drugs . However , the decrease in score was more with citalopram ( p < 0.05 ) . Onset of action of citalopram  was earlier as compared to sertraline ( p < 0.05 ) . The number of responders and remitters was also more with citalopram ( p < 0.05 ) . No serious adverse event was reported in either of the groups . CONCLUSION Citalopram had shown better efficacy , earlier onset of action and more number of responders and remitters as compared to sertraline in MDD in Indian patients Abstract There is evidence of derangement of oxidant and antioxidant defense systems in depression . The present study examined the effects of fluoxetine and citalopram , st and ard selective serotonin re-uptake inhibitors , on lipid peroxidation , superoxide dismutase ( SOD ) activity and ascorbic acid concentrations . For this , a prospect i ve open-labeled , r and omized design was utilized . Patients with major depression ( n = 62 ) were compared with age- and sex-matched healthy volunteers ( n = 40 ) . There was a significant increase in serum SOD , serum MDA and decrease in plasma ascorbic acid levels in patients of major depression as compared to control subjects . The trend reversed significantly after treatment with fluoxetine and citalopram . Results indicate a greater reduction in oxidative stress with citalopram than fluoxetine . The Hamilton Rating Scale for Depression ( HRSD ) score also improved with fluoxetine and citalopram treatment . These findings indicate that major depression is associated with increased levels of serum SOD , serum MDA and decreased levels of plasma ascorbic acid . Treatment with fluoxetine and citalopram reversed these biochemical parameters . This study can be used as a predictor of drug response by fluoxetine and citalopram in major depression To investigate the safety and tolerability of the atypical antipsychotic quetiapine in anorexia nervosa patients , and to determine the effect of quetiapine treatment on anorexic psychopathology and other key outcome measures including weight and body image , we conducted a naturalistic , open-label , 12-week r and omized controlled trial of low-dose ( 100 - 400 mg/day ) quetiapine treatment versus treatment as usual in 33 anorexia nervosa patients from our Eating Disorder Clinics . To monitor the effects of treatment over the medium term , the participants were then followed up with assessment visits at 6 and 12 months after the end of the treatment phase . Low-dose quetiapine treatment result ed in both psychological and physical improvements , with minimal associated side-effects . Given the overall trend toward improvement that we observed , quetiapine appears to be a promising c and i date for the treatment of anorexia nervosa . Further large-scale placebo-controlled clinical trials will be necessary to fully evaluate the benefits of quetiapine treatment for this disorder Patients with Major Depressive Disorder ( MDD ) may not respond to antidepressants for 8 weeks or longer . A biomarker that predicted treatment effectiveness after only 1 week could be clinical ly useful . We examined a frontal quantitative electroencephalographic ( QEEG ) biomarker , the Antidepressant Treatment Response ( ATR ) index , as a predictor of response to escitalopram , and compared ATR with other putative predictors . Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study . After 1 week of treatment with escitalopram , 10 mg , a second QEEG was performed , and the ATR was calculated . Subjects then were r and omly assigned to continue with escitalopram , 10 mg , or change to alternative treatments . Seventy-three evaluable subjects received escitalopram for a total of 49days . Response and remission rates were 52.1 % and 38.4 % , respectively . The ATR predicted both response and remission with 74 % accuracy . Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors . Responders had larger decreases in Hamilton Depression Rating Scale ( Ham-D(17 ) ) scores at day 7 ( P=0.005 ) , but remitters did not . Clinician prediction based upon global impression of improvement at day 7 did not predict outcome . Logistic regression showed that the ATR and early Ham-D(17 ) changes were additive predictors of response , but the ATR was the only significant predictor of remission . Future studies should replicate these results prior to clinical use Approximately 30–45 % of patients with major depressive episode ( MDE ) do not fully respond to st and ard recommended treatments and further strategies of intervention , including pharmacological augmentation , have been proposed for these patients . This study was aim ed to evaluate the efficacy of short-term , low-dose ( 10 mg/day ) intravenous ( i.v . ) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors ( SSRIs ) . Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders , 4th edition , text revision criteria MDE and partial or no response to oral SSRIs were selected and r and omly assigned to citalopram ( n=18 ) or to placebo ( n=18 ) i.v . augmentation . The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs . Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery – Asberg Depression Rating Scale total scores , administered daily with blind-raters conditions , were done . With regard to the Hamilton Depression Rating Scale total scores , a significant time effect ( F=42.02 , P<0.0001 ) and timextreatment effect ( F=21.17 , P<0.0001 ) were found in favor of citalopram . Similar results were obtained from the analysis on Montgomery – Asberg Depression Rating Scale total scores : time effect ( F=50.07 , P<0.0001 ) , timextreatment effect ( F=19.91 , P<0.0001 ) , and treatment effect ( F=4.07 , P=0.05 ) . Even though referred to a small sample , the present findings seem to suggest that short-term , low-dose , i.v . citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs . Further controlled studies performed with double-blind conditions are warranted to confirm the present results Abstract Objectives . Evidence in favour of switching between selective serotonin reuptake inhibitor ( SSRI ) and tricyclic ( TCA ) antidepressants in treatment resistant depression has been tested in a few studies only , consequently a prospect i ve study was undertaken to evaluate the impact of switching strategies . Methods . One hundred eighty-nine patients who failed to respond to a previous antidepressant were r and omised to four arms : firstly they received citalopram or desipramine for a 4-week period ; secondly , those who failed to respond were treated for a further 4-week period with the same antidepressant ( citalopram-citalopram and desipramine-desipramine arms ) or switched to the alternate one ( citalopram-desipramine and desipramine-citalopram arms ) . Results . There was no difference in the first 4-week phase between patients receiving citalopram versus desipramine in Hamilton Rating Scale for Depression ( HRSD ) , Montgomery – Asberg Depression Rating Scale ( MADRS ) , and Clinical Global Impression ( CGI ) scores . In the second 4-week phase remitter rates were higher among non-switched patients ( P = 0.04 ) . Moreover , considering HRSD and MADRS , switched patients reported significantly higher scores ( P ≤ 0.02 for both scales at each time-point ) . Conclusions . This study supports the thesis that switching from an SSRI to a TCA ( and vice versa ) in non-responders to a 4-week trial of an SSRI/TCA is not associated with improved response . The result goes in the opposite direction to that predicted by current guidelines In this pilot study , the pharmacokinetics of citalopram ( CIT ) were examined in five hospitalized depressed patients after an abrupt discontinuation of a treatment with 40 mg/d of this selective serotonin reuptake inhibitor ( SSRI ) .  During the 8-day study period , clinical ratings were regularly carried out . Between days 5 and 8 , the patients were treated with clomipramine ( 75 mg/d ) . The enantiomers of CIT and its metabolites , demethyl-CIT ( DCIT ) and CIT-propionic acid derivative ( CIT-PROP ) , were measured repeatedly from day 0 to day 8 by a stereoselective high-performance liquid chromatography ( HPLC ) procedure . The following drug plasma half-lives were measured ( means + /- SD ) : R-CIT : 66+/-11 h ; S-CIT : 42+/-13 h ; R-DCIT : 228+/-148 h ; S-DCIT : 93+/-35 h ; R-CIT-PROP : 82+/-31 h ; S-CIT-PROP : 186+/-93 Objective . Depression with psychotic features is a severe subtype of major depression associated with the presence of delusions , hallucinations and specific neurobiological features . Despite clinical consensus and guideline recommendations , data comparing the efficacy of combining antipsychotics with antidepressants compared to antidepressants alone remain inconclusive . The aim of the study was to investigate effectiveness and tolerability of the atypical antipsychotic olanzapine in acute depression with psychotic features . Methods . Seventeen in patients with major depressive disorder with psychosis ( MDDp ) were treated with a combination of an antidepressant and olanzapine for 6 weeks in a prospect i ve open-label study . Depressive and psychotic symptoms , extrapyramidal and general side effects were assessed every 2 weeks . Sixteen patients were eligible for final analysis . Results . The Brief Psychiatric Rating Scale ( BPRS ) showed a 30 % symptom reduction after week 2 , a 45 % symptom reduction after week 4 and no considerable improvement thereafter . Depressive symptoms ( Bech – Rafaelsen Melancholia Scale , BRMS ) receded by 37 % after week 2 and 50 % after week 4 . No extrapyramidal side effects occurred . Conclusion . Olanzapine is effective and tolerable in combination with an antidepressant in an MDDp inpatient sample . The results concur with data supporting good efficacy in negative and depressive symptoms of patients with schizophrenic and schizoaffective diseases BACKGROUND Escitalopram has been proven safe and efficacious in the treatment of major depressive disorder ( MDD ) in short-term studies . The long-term clinical tolerability and response to treatment are presented from a 12-month open-label study with a total exposure time to escitalopram of 486 patient years . METHODS Patients ( n = 590 ) with MDD entered the study after completing one of two 8-week , double-blind , placebo-controlled , lead-in studies in primary care . Escitalopram was administered at doses of 10 or 20 mg/day ( dose based on physician 's clinical judgement ) with an average exposure to escitalopram of 315 days . The primary efficacy parameter was the Montgomery Asberg Depression Rating Scale ( MADRS ) total score . RESULTS The overall withdrawal rate was 26 % ; and the withdrawal rate due to adverse events was 9 % . The most common adverse events were headache , back pain , upper respiratory tract infection , rhinitis and nausea , with an incidence ranging from 11 % to 17 % . No new types of adverse events were seen after the acute period of 8 weeks , and the incidence declined with time . At baseline ( entry into the 12-month study ) , patients had a mean MADRS total score of 14.2 , which decreased to 10.5 after 8 weeks and 7.2 after 52 weeks ( LOCF ) . The percentage of patients in remission ( MADRS total score < /=12 ) increased from 46 % at baseline to 65 % by Week 8 and 86 % by Week 52 . CONCLUSIONS Escitalopram ( 10 to 20 mg/day ) demonstrated a favorable safety and tolerability profile over 12-months treatment , with further improvement in patient response Antidepressants are used to treat chronic daily headache disorders such as  migraine  and chronic tension-type headache ( TTH ) , which are often associated with depression and anxiety . Here , we studied the efficacy and tolerability of amitriptyline and citalopram , given alone or in combination , in patients with ‘ triple ’ comorbidity of depression , TTH , and migraine . Eighty-eight patients were enrolled in the study and r and omly divided into two groups . The first group received amitriptyline and the second citalopram for 16 weeks . Patients were assessed at weeks 0 , 4 , 8 , and 16 . The two drugs were equally efficacious in relieving depressive symptoms , although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks . Patients who did not respond to monotherapy ( < 30 % of improvement in the clinical scores ) were treated with a combination of the two drugs for 16 additional weeks . In these selected patients , the combined treatment produced a substantial improvement in depression , migraine and TTH without producing major side effects such as those commonly related to the ‘ serotonergic ’ syndrome . The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH , migraine and comorbid depression that do not respond to monotherapy BACKGROUND This study examined the potential of an antidepressant drug , escitalopram , to improve depression , resilience to stress , and quality of life in family dementia caregivers in a r and omized placebo-controlled double-blinded trial . METHODS Forty family caregivers ( 43 - 91 years of age , 25 children and 15 spouses ; 26 women ) who were taking care of their relatives with Alzheimer disease were r and omized to receive either escitalopram 10 mg/day or placebo for 12 weeks . Severity of depression , resilience , burden , distress , quality of life , and severity of care-recipient 's cognitive and behavioral disturbances were assessed at baseline and over the course of the study . The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28 . The groups were stratified by the diagnosis of major and minor depression . RESULTS Most outcomes favored escitalopram over placebo . The severity of depression improved , and the remission rate was greater with the drug compared with placebo . Measures of anxiety , resilience , burden , and distress improved on escitalopram compared with placebo . DISCUSSION Among caregivers , this small r and omized controlled trial found that escitalopram use result ed in improvement in depression , resilience , burden and distress , and quality of life . Our results need to be confirmed in a larger sample Negative cognitive structure ( particularly for interpersonal content ) has been shown in some research to persist past a current episode of depression and potentially to be a stable marker of vulnerability for depression ( D. J. A. Dozois , 2007 ; D. J. A. Dozois & K. S. Dobson , 2001a ) . Given that cognitive therapy ( CT ) is highly effective for treating the acute phase of a depressive episode and that this treatment also reduces the risk of relapse and recurrence , it is possible that CT may alter these stable cognitive structures . In the current study , patients were r and omly assigned to CT+ pharmacotherapy ( n = 21 ) or to pharmacotherapy alone ( n = 21 ) . Both groups evidence d significant and similar reductions in level of depression ( as measured with the Beck Depression Inventory-II and the Hamilton Rating Scale for Depression ) , as well as automatic thoughts and dysfunctional attitudes . However , group differences were found on cognitive organization in favor of individuals who received the combination of CT+ pharmacotherapy . The implication s of these results for underst and ing mechanisms of change in therapy and the prophylactic nature of CT are discussed
target: Some statistically significant differences between citalopram and other antidepressants for the acute phase treatment of major depression were found in terms of efficacy , tolerability and acceptability .
  Citalopram was more efficacious than paroxetine and reboxetine and more acceptable than tricyclics , reboxetine and venlafaxine , however , it seemed to be less efficacious than escitalopram .
background: BACKGROUND Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode .
  Systematic review s have already highlighted some differences in efficacy between second-generation antidepressants .
  Citalopram , one of the first selective serotonin reuptake inhibitors ( SSRI ) introduced in the market , is one of these antidepressant drugs that clinicians use for routine depression care .
  OBJECTIVES To assess the evidence for the efficacy , acceptability and tolerability of citalopram in comparison with tricyclics , heterocyclics , other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression .