title: Lack of drug interactions between mirtazapine and risperidone in psychiatric patients: a pilot study Impaired declarative memory in depressed patients is slow to recover: clinical experience. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression Distinct mechanism for antidepressant activity by blockade of central substance P receptors. A randomized, double‐blind, 24‐week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care Paroxetine and amitriptyline in the treatment of depression in general practice Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Cardiovascular effects of paroxetine Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. A study comparing paroxetine placebo and imipramine in depressed patients. A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. A comparison of paroxetine, imipramine and placebo in depressed out-patients. Clinical and Neurobiological Effects of Tianeptine and Paroxetine in Major Depression Resolution of sexual dysfunction during double-blind treatment of major depression with reboxetine or paroxetine Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison. A 12‐week double‐blind multi‐centre study of paroxetine and imipramine in hospitalized depressed patients Paroxetine and imipramine treatment of depressive patients in a controlled multicentre study with plasma amino acid measurements A comparative study of milnacipran and paroxetine in outpatients with major depression. A Double‐Blind Multicentre Study of Paroxetine and Amitriptyline in Depressed Outpatients Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study. Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients. GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol Venlafaxine vs. paroxetine in the acute phase of treatment for major depressive disorder among Han Chinese population in Taiwan. A multicenter double-blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate-to-severe depression. Reboxetine versus paroxetine versus placebo: effects on cognitive functioning in depressed patients Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial Paroxetine in the Treatment of Elderly Depressed Patients in General Practice: A Double‐Blind Comparison with Amitriptyline A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine [Paroxetine in the treatment of depression in geriatric patients--a double-blind comparative study with fluoxetine]. A Double-Blind, Multicentre Study to Assess the Tolerability and Efficacy of Paroxetine Compared with Amitriptyline in the Treatment of Depressed Patients in Australian General Practice A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. Acute Efficacy of Fluoxetine Versus Sertraline and Paroxetine in Major Depressive Disorder Including Effects of Baseline Insomnia Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism Selective serotonin reuptake inhibitor treatment of depression in symptomatic HIV infection and AIDS. Improvements in affective and somatic symptoms. Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. Do venlafaxine XR and paroxetine equally influence negative and positive affect? Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Sleep and Paroxetine: A Comparison with Mianserin in Elderly Depressed Patients Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression. Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine Assessing risk of bias in randomized controlled trials. A Double‐Blind Study of Paroxetine Compared With Fluoxetine in Geriatric Patients With Major Depression Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials. Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil. A Multicenter Double‐Blind Trial of Paroxetine Versus Amitriptyline in Depressed Inpatients Serotonergic function in major depression and effect of sertraline and paroxetine treatment Efficacy of controlled-release paroxetine in the treatment of late-life depression. A double‐blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. Clinical experience with substance P receptor (NK1) antagonists in depression. A double-blind study comparing paroxetine and maprotiline in depressed outpatients. Paroxetine versus amitriptyline in patients with recurrent major depression: A double-blind trial A critical examination of the sensitivity of unidimensional subscales derived from the Hamilton Depression Rating Scale to antidepressant drug effects. Mirtazapine compared with paroxetine in major depression. Effects of the Serotonin Type 2A, 3A and 3B Receptor and the Serotonin Transporter Genes on Paroxetine and Fluvoxamine Efficacy and Adverse Drug Reactions in Depressed Japanese Patients Venlafaxine XR demonstrates higher rates of sustained remission compared to fluoxetine, paroxetine or placebo A double-blind comparison of the efficacy and safely of paroxetine and imipramine in the treatment of depression with dementia. Prevalence of sexual dysfunction among newer antidepressants. Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out‐patients with inadequate treatment response Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. Antidepressive Treatment with Amitriptyline and Paroxetine: Effects on Saliva Cortisol Concentrations Open-label non-randomized versus double-blind randomized antidepressive treatment: what are the advantages of clinical decision over randomization? Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder [Multicenter double-blind study comparing the efficacy and tolerance of paroxetine and clomipramine in reactive depression in the elderly patient]. A Double-Blind, Multicentre Study of Paroxetine and Maprotiline in Major Depression A Double‐Blind, Randomized, Fluoxetine‐Controlled, Multicenter Study of Paroxetine in the Treatment of Depression A double-blind, multicenter study in primary care comparing paroxetine and clomipramine in patients with depression and associated anxiety. Paroxetine Study Group. Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT2C antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study Efficacy and Safety of Tianeptine in Major Depression A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. Relationship between parameters of serotonin transport and antidepressant plasma levels or therapeutic response in depressive patients treated with paroxetine and amitriptyline Paroxetine and imipramine in the treatment of depressive patients in psychiatric practice Mirtazapine is more effective than trazodone: a double‐blind controlled study in hospitalized patients with major depression Paroxetine in the treatment of depression: a comparison with imipramine and placebo Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. A double-blind randomized comparison of nortriptyline and paroxetine in the treatment of late-life depression: 6-week outcome. Paroxetine in the treatment of depression A placebo- and imipramine-controlled study of paroxetine. Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression. Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression. Double-blind comparison of paroxetine and nortriptyline on the postural stability of late-life depressed patients. [Comparative study of paroxetine and mianserin in depression in elderly patients: efficacy, tolerance, serotonin dependence]. Paroxetine in the treatment of depression ‐ a randomized comparison with amitriptyline A double‐blind study to compare the effectiveness and tolerability of paroxetine and amitriptyline in depressed patients Response to treatment in minor and major depression: results of a double-blind comparative study with paroxetine and maprotiline. Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. A double‐blind study of the comparative antidepressant effect of paroxetine and amitriptyline Endogenous concentrations of DHEA and DHEA-S Decrease with remission of depression in older adults A 6-week, double-blind trial of paroxetine, imipramine, and placebo in depressed outpatients. Duloxetine in the treatment of depression: A double-blind placebo-controlled comparison with paroxetine Mirtazapine and paroxetine in major depression: A comparison of monotherapy versus their combination from treatment initiation A double-blind comparison of paroxetine, imipramine, and placebo in major depression. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors? Efficacy and safety of amisulpride 50 mg versus paroxetine 20 mg in major depression: a randomized, double-blind, parallel group study Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study Development of an antidepressant compliance questionnaire Treatment of major depression in general practice: a double-blind comparison of paroxetine and lofepramine. Are serotonergic reuptake inhibitors more potent in reducing suicidality? An empirical study on paroxetine Effects of Paroxetine and Venlafaxine XR on Heart Rate Variability in Depression Direct Cost of Depression: Analysis of Treatment Costs of Paroxetine versus Imipramine in Canada Double-blind comparative study of paroxetine and amitriptyline in depressed patients of a university psychiatric outpatient clinic (pilot study). Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
abstract: An open-label , non-r and omized , pilot study has been performed in in patients in need of treatment with an antipsychotic ( risperidone ) and an antidepressant ( mirtazapine )  with the objective to preliminarily assess a possible pharmacokinetic interaction and the tolerability of this combination . A 1 - 4-week single drug treatment phase ( risperidone 1 - 3 mg bid or mirtazapine 30 mg nocte ) was followed by a 2 - 4-week combined drug treatment phase at unchanged doses . Twelve patients were enrolled , nine of whom were treated with risperidone  in the single drug phase . Results of plasma level measurements are available for six patients and indicate that adding mirtazapine to risperidone does not alter steady-state plasma concentrations of risperidone and its 9-hydroxy metabolite . Data from one patient suggest that adding risperidone to mirtazapine does not result in clinical ly relevant changes in plasma concentrations of either compound . The combination was well tolerated and no major or relevant adverse events were observed . Adding risperidone to mirtazapine probably does not necessitate a change of the dosage of either drug , but more extensive investigations are needed INTRODUCTION The temporal course of recovery of depressed patients ' cognitive impairment is not fully understood . METHODS We used the California Verbal Learning Test ( CVLT ) to test declarative memory in 24 depressed patients before and after 35 days of antidepressive treatment as well as after long-term follow-up ( > 12 months ) in order to relate improvement of depression to recovery of cognitive impairment . RESULTS Patients with complete remission after 35 days had generally been less impaired at baseline . The disturbance of declarative memory in treatment responders as well as in non-responders did not change from baseline to end of treatment ( day 35 ) . However , our results revealed normal values in the CVLT sum score as well as in measures of short- and long-delay free-recall measures in both groups after long-term full remission . DISCUSSION We conclude that clinical response to antidepressive treatment precedes improvement of declarative memory . A low degree of impairment of declarative memory is associated with early complete remission of depression 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 This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties . Like clinical ly used antidepressant and anxiolytic drugs , substance P antagonists suppressed  isolation-induced vocalizations in guinea pigs . In a placebo-controlled trial in patients with moderate to severe major depression , robust antidepressant effects of the substance P antagonist MK-869 were consistently observed . In pre clinical studies , substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs . These findings suggest that substance P may play an important role in psychiatric disorders & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine  30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors Christiansen PE , Behnke K , Black CH , Öhrström JK , Bork‐Rasmussen H , Nilsson J. Paroxetine and amitriptyline in the treatment of depression  in general practice . Acta Psychiatr Sc and 1996 : 93 : 158–163 . © Munksgaard 1996 OBJECTIVE Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder ( MDD ) . METHODS In this r and omized , double-blind trial , patients age > or = 18 meeting DSM-IV criteria for MDD were r and omized to placebo ( N=99 ) , duloxetine 80 mg/day ( N=93 ) , duloxetine 120 mg/day ( N=103 ) , or paroxetine 20 mg/day ( N=97 ) . The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression ( HAMD(17 ) ) total score after 8 weeks of treatment ; a number of secondary efficacy measures also were assessed . Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events ( TEAEs ) , vital signs , and weight . The Arizona sexual experiences scale was used to assess sexual functioning . Patients who had a > or = 30 % reduction from baseline in the HAMD(17 ) total score  at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase ; efficacy and safety/tolerability outcomes were assessed during continuation treatment . RESULTS More than 87 % of patients completed the acute phase in each treatment group . Duloxetine-treated patients ( both doses ) showed significantly greater improvement ( P<0.05 ) in the HAMD(17 ) total score at week 8 compared with placebo . Paroxetine was not significantly different from placebo ( P=0.089 ) on mean change on the HAMD(17 ) .  Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures ( six of nine ) compared with placebo while duloxetine 80 mg/day ( three of nine ) and paroxetine ( three of nine ) were significantly superior to placebo on fewer secondary measures . HAMD(17 ) mean change data from this study and an identical sister study were pooled as defined a priori for the purpose s of performing a non-inferiority test versus paroxetine . Both duloxetine doses met statistical criteria for non-inferiority to paroxetine .  TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases . CONCLUSIONS The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated . Tolerability , as measured by TEAEs , and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD In a double-blind clinical study , electrocardiogram , blood pressure and systolic time intervals were measured in 40 depressive patients treated with either paroxetine ( 30 mg/day ) or amitriptyline ( 150 mg/day ) for 6 weeks . While amitriptyline significantly increased the heart rate , the QTc interval and the PEP/LVET ratio , paroxetine did not alter any of the cardiovascular parameters measured OBJECTIVE Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase ( 8 weeks ) and an extension phase ( 16 weeks ) . METHODS Patients with major depression and without dementia , at least 65 years old , were eligible ; they were r and omized to mirtazapine or paroxetine once daily , with doses increasing over 42 days . Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale , and tolerability was assessed from adverse events . RESULTS Of 255 patients r and omized , 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis . Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score . Other significant differences were in the proportion of patients classified as responders ( 50 % decrease from baseline Ham-D-17 scores ) at Day 14 and in remission ( Ham-D-17 score of 7 or less ) at Day 42 . The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group . The mirtazapine group also showed more reduction in Ham-D Factor I ( Anxiety/Somatization ) and Factor VI ( Sleep Disturbance ) scores . Efficacy of both drugs was maintained during the extension phase . Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events . CONCLUSION During the first weeks of treatment , antidepressant effects were more pronounced in the mirtazapine group , suggesting that mirtazapine has an earlier onset of action . Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients These data provide evidence for the antidepressant efficacy of paroxetine . Paroxetine- and imipramine-treated patients were significantly different from  placebo-treated patients , but little different to each other , on all depressive outcome measures . However , paroxetine appeared to have a possibly greater and earlier beneficial effect on anxiety symptoms associated with depression , when compared with imipramine . Both active therapies were effective in treating patients with severe depression . Side effects for paroxetine were typical of other serotonin ( 5-HT ) uptake inhibitors but different from those of imipramine . In particular , anticholinergic and cardiovascular symptoms were reduced , and premature withdrawal less likely BACKGROUND Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors . In a 12-week r and omized , multicenter , double-blind trial , the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression . METHODS A total of 203 patients were r and omized to fixed doses ( 20 mg/day ) of paroxetine or fluoxetine for the first six weeks of therapy . From week 7 - 12 , dosing could be adjusted biweekly , as required ( paroxetine 20 - 50 mg/day , and fluoxetine 20 - 80 mg/day ) . The mean prescribed doses were paroxetine 25.5 mg/day ( range 20.0 - 40.2 mg/day ) , and fluoxetine 27.5 mg/day ( range 20.0 - 59.5 mg/day ) . Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia . RESULTS Both active treatments demonstrated comparable antidepressant efficacy ( HAM-D , CGI ) . Anxiolytic activity of the two drugs ( COVI , STAI , HAM-D ) was also comparable . However , paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy ( HAM-D Agitation item , p < 0.05 ; Psychic Anxiety item , p < 0.05 ) , with no differences detected after week 2 . The overall incidence of adverse effects was comparable in the two treatment groups . Constipation , dyspepsia , tremor , sweating and abnormal ejaculation were more common in paroxetine-treated subjects , whereas nausea and nervousness were more frequent in fluoxetine-treated patients . Weight loss was more common in the fluoxetine versus paroxetine group ( 11.88 % versus 2.94 % , respectively ) . ESRS scores for akathisia were low throughout the study and showed little change . LIMITATIONS Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others . DISCUSSION The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy .  Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine To compare the safety and antidepressant efficacy of paroxetine , imipramine , and placebo , data from six centres using the same protocol were pooled . A double-blind parallel-group design was used , with therapy lasting six weeks . From week 2 onwards , both the 240 paroxetine-treated and the 237 imipramine-treated patients were significantly different from the 240 placebo-treated patients , but no different from each other . Side-effects with paroxetine were less likely to lead to drop-out than with imipramine . Paroxetine had a possible earlier antidepressant effect than imipramine , and a possible earlier beneficial effect on anxiety symptoms associated with depression Selective serotonin reuptake inhibitors ( SSRIs ) are widely used as effective pharmacological agents to treat depressive disorders . In contrast to the SSRIs , which block the presynaptic serotonin ( 5-HT ) transporter and by this route increase the concentration of serotonin in the synaptic cleft , the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission . Both SSRIs and tianeptine are clinical ly effective ; however , their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission . To better underst and the differences between these two opposite pharmacological modes of action , we compared the changes induced by tianeptine and paroxetine on psychopathology , the hypothalamic-pituitary-adrenocortical ( HPA ) system , and cognitive functions in a double-blind , r and omized , controlled trial including 44 depressed in patients over a period of 42 days .  Depressive symptomatology significantly improved in all efficacy measures , with no significant differences between tianeptine and paroxetine . There was a trend toward better response to the SSRI among women . Assessment of the HPA system showed marked hyperactivity before the beginning of treatment , which then normalized in most of the patients , without significant differences between the two antidepressants . Cognitive assessment s showed no significant differences between the two drugs investigated . The results of the current study suggest that the initial effect , i.e. , enhancement or decrease of 5-HT release , is only indirectly responsible for antidepressant efficacy , and they support the notion that downstream adaptations within and between nerve cells are crucial . The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest 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 About one-third of patients fail to respond to initial antidepressant therapy , which suggests a need for more effective drugs . AIMS To compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression . METHOD In- patients or out- patients satisfying DSM-III-R criteria for major depression in evolution for less than eight months , having a baseline HAM-D score > or = 18 and a HAM-D Item 3 score < 3 were eligible . Patients were required to have a history of resistance to two previous antidepressant treatments and a CGI improvement score of 3 at the beginning of treatment . Doses were adjusted to 200 - 300 mg/day for venlafaxine and 30 - 40 mg/day for paroxetine . RESULTS For the observed-case analysis , the response rate was 51.9 % for venlafaxine and 32.7 % for paroxetine ( P = 0.044 ) , and a remission was achieved in 42.3 % of venlafaxine-treated and 20.0 % of paroxetine-treated patients ( P = 0.01 ) . The incidence of adverse effects was comparable between treatment groups . CONCLUSIONS Venlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population Fifty‐seven in patients with major depression ( DSM‐III‐R ) entered a 12‐week study comparing paroxetine and imipramine . Trends ( not reaching statistical significance ) in favour of paroxetine were seen on the Hamilton Depression Rating Scale ( HDRS ) and the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) . The UKU Side Effect Rating Scale showed a significant difference in favour of paroxetine on reduced salivation . Global evaluation of side effect symptoms showed that significantly more paroxetine patients had no side effects , both in the investigators ’ and the patients ’ opinion . These results are in line with previous findings of paroxetine being an effective and well tolerated antidepressant In a 12‐week double‐blind study with 36 patients with major depressive episode ( DSM‐III ) , paroxetine ( Seroxat ® Aropax ® showed significantly quicker onset of efficacy on the Melancholia Scale , and better tolerance than imipramine . Plasma concentration analyses showed no clear concentration‐efficacy correlation in either treatment group . During long‐term treatment paroxetine seemed to be superior to imipramine in preventing relapse : both treatments were well tolerated . A significant correlation between baseline plasma tryptophan : large neutral amino acids ratio and final Hamilton Rating Scale for Depression ( HRSD ) score and a trend towards an inverse correlation between this ratio and percentage reduction in HRSD score were seen in the paroxetine group but not in the imipramine group . In line with previous studies , these results support the hypothesis that paroxetine is an effective and well tolerated antidepressant 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 A comparative double-blind study of paroxetine and amitriptyline in the treatment of depressed hospital out patients was undertaken at 15 centres in Italy . Three hundred and nine patients of either sex were admitted to the study . The starting dose of paroxetine was 20 mg daily and of amitriptyline 75 mg daily in divided doses ; at week 3 these doses could be increased at the investigators ' discretion . Efficacy was measured on the Hamilton Depression Rating Scale and on Clinical Global Impression . Both treatment groups showed significant improvement at week 6 with no significant between-group differences . Significantly fewer patients receiving paroxetine reported adverse events compared with those on amitriptyline ( 44 % vs 62 % ; p < 0.01 in favour of paroxetine ) OBJECTIVE To compare the efficacy and tolerability of paroxetine ( a selective serotonin reuptake inhibitor ) with that of amitriptyline ( a tricyclic antidepressant ) in the treatment of depression in 191 patients with rheumatoid arthritis ( RA ) . METHODS A r and omized , double blind , double dummy , parallel group study . A placebo washout period of 3 - 7 days was followed by an 8 week active treatment phase during which patients received either paroxetine ( 20 - 40 mg daily ) or amitriptyline ( 75 - 150 mg daily ) . The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint . RESULTS Paroxetine was as effective as amitriptyline for the treatment of depression , with similar improvements in RA associated pain and disability also seen in both groups . However , paroxetine was better tolerated than amitriptyline , with an overall frequency of adverse experiences of 56.4 % and 67.7 % in the 2 groups , respectively . The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group ( 18.1 % vs 43.8 % taking amitriptyline ) and paroxetine treated patients also experienced fewer severe ( 16.0 % vs 21.9 % ) , serious nonfatal ( 0 % vs 4.2 % ) , and drug related adverse experiences ( 12.8 % vs 29.2 % ) . CONCLUSION Tolerability is an important consideration in this patient population , which is largely composed of elderly patients who are taking additional medications for RA .  Paroxetine shows a number of advantages in the management of depression comorbid with RA BACKGROUND This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety , quality of life , disability , and metabolic control in type II diabetes mellitus ( DM ) patients . METHODS The patients were first applied the Hospital Anxiety-Depression Scale ( HADS ) . After a psychiatric interview with patients who had scores above the cut-off point , those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale ( HDRS ) and the Hamilton Anxiety Rating Scale ( HARS ) .  Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 ( SF-36 ) , and the Brief Disability Question naire ( BDQ ) and HbA1c levels were measured . Patients were r and omized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment . The patients were evaluated with the same scales at the 2(nd ) , 4(th ) , 6(th ) , and the 12(th ) weeks . RESULTS Both groups showed a statistically significant decrease in HDRS , HARS , and BDQ scores with comparison to the index assessment . At the end of treatment , though not statistically significant , a decrease was observed in HbA1c values of the fluoxetine-administered group . CONCLUSIONS Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients . There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control 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 PURPOSE Clinical studies have suggested that venlafaxine induces a higher remission rate than paroxetine . However , very few studies have evaluated relapse episodes over treatment periods longer than a few weeks , and the cut-off score of 7 on the Hamilton Rating Scale for Depression ( HRSD ) often used to define remission is too high . This score is associated with the high rates of social function impairment . We report on a single centre , open-label , prospect i ve 24-week study to investigate the comparative efficacy of acute treatments with venlafaxine and paroxetine , using different definitions of response and remission rates . METHODS Out patients satisfying DSM-IV criteria for major depression with a baseline HRSD17 score of at least 16 were eligible . Following baseline evaluations , the patients were assigned to receive venlafaxine 75 - 225 mg/day with the mean dosage 141.35 + /- 26.98 ( SD ) mg/day ( n = 78 ) , or paroxetine 20 mg/day ( n = 92 ) for 24 weeks . Efficacy was assessed using the mean change in HRSD(17 ) score from baseline , the response rate and the remission rates based on different criteria for remission ( HRSD(17 ) score < or = 7 or 5 ) . RESULTS One hundred and seventy patients were evaluated for efficacy ; 78 treated with venlafaxine and 92 with paroxetine .  Over the treatment period , venlafaxine was comparable with paroxetine on most outcome measures , whereas paroxetine produced significantly higher remission rates at weeks 4 , 8 , 16 , 20 and 24 weeks when the lower cutoff of 5 was used . CONCLUSIONS Venlafaxine treatment was similar to paroxetine according to the typical efficacy measures for treating out patients with major depression . However , based on the stricter remission criterion , paroxetine might be superior to venlafaxine BACKGROUND The efficacy , safety , and tolerance of nefazodone and paroxetine in the treatment of depressed out patients were compared in a r and omized , double-blind parallel group study at 20 centers in the United Kingdom and Republic of Irel and . METHOD The study population comprised 206 out patients meeting DSM-III-R criteria for a moderate-to-severe nonpsychotic major depressive episode . Patients considered to be at serious risk of suicide were excluded from participation in the study . After a drug-free baseline phase of 1 to 4 weeks , patients were r and omly assigned to treatment with either nefazodone or paroxetine . Outcome measures for efficacy included the Clinical Global Impressions scales , Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , Montgomery-Asberg Depression Rating Scale , and Patient Global Assessment scale . Tolerance and safety were assessed using spontaneously reported adverse events , vital signs , and laboratory investigations . RESULTS There were no significant differences between the groups in clinical outcome . Analysis of the efficacy measures revealed a consistent and continuous improvement in both groups . A similar proportion of patients in each group discontinued treatment owing to adverse events : 15 ( 14 % ) in the nefazodone group and 13 ( 13 % ) in the paroxetine group . CONCLUSION Nefazodone and paroxetine have similar efficacy and tolerability in the treatment of out patients with major depression Impaired cognitive functioning is often associated with major depressive disorder ( MDD ) . Moreover , a number of agents used to treat MDD are known to have negative effects on cognitive functioning . We report an assessment of the effects of the selective norepinephrine reuptake inhibitor reboxetine , the selective serotonin reuptake inhibitor paroxetine , and placebo on a variety of measures of cognitive functioning in patients with MDD.Cognitive  functioning in 74 adult patients ( aged 18–65 years ) with a confirmed diagnosis of MDD ( DSM-IV ) was assessed as part of two identical , r and omized , double-blind , placebo- and active-treatment-controlled , fixed/flexible dose comparisons of 8 weeks of treatment with reboxetine ( 8–10 mg/day ) , paroxetine ( 20–40 mg/day ) and placebo .  Cognitive function was assessed at baseline , day 14 and day 56 using a selection of tasks from the Cognitive Drug Research computerized assessment system , including Simple Reaction Time , Digit Vigilance , Choice Reaction Time , Numeric Working Memory , Word Recognition and Critical Flicker Frequency . The results in the 74 patients  ( reboxetine n = 25 , paroxetine n = 23 , placebo n = 26 ) showed that reboxetine significantly improved the ability to sustain attention at day 56 compared with baseline ( P = 0.023 ) . In addition , patients who received reboxetine experienced significant improvements in their speed of cognitive functioning when tested at day 56 compared to baseline ( P = 0.024 ) . No significant changes or trends in this direction were seen among patients who received either placebo or paroxetine . The results of the present study provide objective data to support the possibility that reboxetine favourably affects cognitive processes in depressed patients BACKGROUND Duloxetine is a balanced and potent dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) that has previously been shown to be effective in the acute treatment of major depressive disorder ( MDD ) . This placebo-controlled study assesses the safety and efficacy of duloxetine ( 80 or 120 mg/day ) and paroxetine ( 20 mg QD ) during an initial 8-week acute phase and subsequent 6-month continuation phase treatment of MDD . METHOD In this r and omized , double-blind , placebo-controlled trial , adult out patients ( age > or= 18 years ) meeting DSM-IV criteria for MDD received placebo ( n = 93 ) , duloxetine 80 mg/day ( 40 mg BID ; n = 95 ) , duloxetine 120 mg/day ( 60 mg BID ; n = 93 ) , or paroxetine ( 20 mg QD ; n = 86 ) for 8 weeks . Patients who had a > or= 30 % reduction from baseline in HAMD(17 ) total score during the acute phase were allowed to continue on the same ( blinded ) treatment for a 6-month continuation phase . Efficacy measures included the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) total score , HAMD(17 ) subscales , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Rating Scale ( HAMA ) , Visual Analog Scales ( VAS ) for pain , the Clinical Global Impression of Severity ( CGI-S ) and Patient Global Impression of Improvement ( PGI-I ) scales , the 28-item Somatic Symptom Inventory ( SSI ) , and the Sheehan Disability Scale ( SDS ) . Safety and tolerability were assessed using treatment-emergent adverse events , discontinuations due to adverse events , vital signs , ECGs , laboratory tests , and the Arizona Sexual Experiences Scale ( ASEX ) . RESULTS During the acute phase , patients receiving duloxetine 80 mg/day , duloxetine 120 mg/day , or paroxetine 20 mg QD had significantly greater reductions in HAMD(17 ) total score compared with placebo . Both duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups had significantly greater improvement , compared with placebo , in MADRS , HAMA , CGI-S , and PGI-I scales . Estimated probabilities of remission at week 8 for patients receiving duloxetine 80 mg/day ( 51 % ) , duloxetine 120 mg/day ( 58 % ) , and paroxetine ( 47 % ) were significantly greater compared with those receiving placebo ( 30 % ) . The rate of discontinuation due to adverse events among duloxetine-treated patients ( 80 and 120 mg/day ) did not differ significantly from the rate in the placebo group . Treatment-emergent adverse events reported significantly more frequently by duloxetine-treated patients than by patients receiving placebo were constipation ( 80 and 120 mg/day ) , increased sweating ( 120 mg/day ) , and somnolence ( 120 mg/day ) . The incidence of acute treatment-emergent sexual dysfunction in duloxetine- and paroxetine-treated patients was 46.5 % and 62.8 % , respectively . During the 6-month continuation phase , duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups demonstrated significant improvement in HAMD(17 ) total score . Treatment-emergent adverse events occurring most frequently in each active treatment group during the continuation phase were viral infection  ( duloxetine 80 mg/day ) , diarrhea  ( duloxetine 120 mg/day ) , and headache  ( paroxetine 20 mg QD ) . CONCLUSION These data support previous findings that duloxetine is safe , efficacious , and well tolerated in the acute treatment of MDD . Furthermore , these data provide the first demonstration under double-blind , placebo-controlled conditions that the efficacy and tolerability of duloxetine are maintained during chronic treatment A total of 101 patients entered a double-blind , parallel-group study in general practice , comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients . All patients received placebo for 1 week followed by active therapy for a total of 6 weeks . Medication was r and omly allocated , two-thirds of the patients took paroxetine ( 20 mg daily ) and one-third received amitriptyline ( 50 mg daily ) ; this dose was increased to 30 mg and 100 mg , respectively , after 1 week . Of the patients who entered the placebo run-in , 90 took active treatment and were evaluable on an intention-to-treat basis ( 56 paroxetine , 32 amitriptyline ) . The mean age of the patients was 72 years . Significant reductions in Hamilton Depression Rating Scale ( HAMD ) from baseline to the end of treatment were seen for both groups ( p < 0.01 ) , with no difference between treatments . The HAMD score was reduced by half , or more , for 76 % of patients taking paroxetine and 86 % taking amitriptyline . Significant improvement was observed in the investigators ' Clinical Global Impression ( CGI ) score for 57 % of patients taking paroxetine and 52 % on amitriptyline . Improvements after treatment were also observed in the Leeds Sleep Evaluation Question naire ( LSEQ ) scores . Significantly fewer patients taking paroxetine reported adverse events ( 34 % vs 63 % taking amitriptyline , p = 0.02 ) . Those taking paroxetine experienced significantly fewer anticholinergic side effects ( 7 % vs 25 % taking amitriptyline , p = 0.04 ) . Overall , this study confirmed the effectiveness of paroxetine as an antidepressant drug . The relatively low incidence of adverse events , compared with amitriptyline , particularly the anticholinergic side effects which may be associated with disturbances in cognitive function , makes paroxetine suitable for the treatment of elderly depressed patients in general practice ABSTRACT Objectives : To evaluate the efficacy and safety of trazodone prolonged release compared with paroxetine in the treatment of patients with major depression . Research design and methods : A total of 108 patients aged 20–68 years were enrolled in this multicentre , double-blind , double-dummy , r and omised , paroxetine-controlled study . Each patient received 3 days single-blind placebo treatment followed by 6 weeks double-blind treatment with either trazodone prolonged release 150–450 mg/day ( n = 55 ) or paroxetine 20–40 mg/day ( n = 53 ) . Outcome measures : Efficacy was evaluated by the rate of patients responding to each treatment and considered to be in remission , and by mean changes from baseline in the Hamilton Depression Rating scale scores ( HAM-D ) , Montgomery Asberg Depression Rating Scale scores ( MADRS ) , and Clinical Global Impression ( CGI ) – Severity and Global Improvement scores . Time to onset of efficacy and safety were assessed . Results : Trazodone and paroxetine were equally effective at reducing symptoms of depression and promoting remission . Onset of efficacy was slightly faster for patients treated with paroxetine . Overall , there were no significant differences between the groups at endpoint in efficacy measures , and in percentage of responders ( > 85 % ) or patients in remission ( > 65 % ) . Sleep disorders ( HAM-D subset ) were significantly less evident for patients in the trazodone group at the end of the study ( p < 0.05 ) . Adverse drug reactions were reported by 35 % of trazodone-treated patients ( mainly of the nervous system ) and 26 % of paroxetine-treated patients ( mainly gastrointestinal ) , although none was considered to be serious . Conclusions : This study showed that after a 6-week period trazodone and paroxetine are not different in reducing the symptoms of depression and , in many patients , in producing the remission of the illness . The known divergence in tolerability profile of the two medications , related to their differing pharmacological properties , was also confirmed . Trazodone may be of advantage in depressed patients with sleep difficulties Abstract Objective To investigate the efficacy of hypericum extract WS 5570 ( St John 's wort ) compared with paroxetine in patients with moderate to severe major depression . Design R and omised double blind , double dummy , reference controlled , multicentre non-inferiority trial . Setting 21 psychiatric primary care practice s in Germany . Participants 251 adult out patients with acute major depression with total score ≥ 22 on the 17 item Hamilton depression scale . Interventions 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks . In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks . Main outcome measures Change in score on Hamilton depression scale from baseline to day 42 ( primary outcome ) . Secondary measures were change in scores on Montgomery-Åsberg depression rating scale , clinical global impressions , and Beck depression inventory . Results The Hamilton depression total score decreased by mean 14.4 ( SD 8.8 ) points , corresponding to 56.6 % ( SD 34.3 % ) of the baseline value , in the hypericum group and by 11.4 ( SD 8.6 ) points ( 44.8 % ( SD 33.5 % ) of baseline value ) in the paroxetine group ( intention to treat analysis ; similar results were observed in the per protocol analysis ) . The intention to treat analysis ( lower one sided 97.5 % confidence limit 1.5 points for the difference hypericum minus paroxetine ) and the per protocol analysis ( lower confidence limit 0.7 points ) showed non-inferiority of hypericum and statistical superiority over paroxetine . The lower limits in both cases exceeded the pre-specified non-inferiority margin of −2.5 points and the superiority margin of 0 . The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine , respectively . Conclusions In the treatment of moderate to severe major depression , hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated A 6-week double-blind , parallel group study compared paroxetine and fluoxetine in 106 depressed geriatric in patients ( aged 65 to 85 years ) . Patients presenting acutely with major depressive episode DSM-III-R 296.2 ( HAMD > 18 on 21 item scale ) were r and omized to receive paroxetine ( 20 - 40 mg , n = 54 ) or fluoxetine ( 20 - 60 mg , n = 52 ) following a 3 - 7 day washout . Primary criteria was the reduction of Hamilton Depression Rating Scale Score ( HAMD ) . Furthermore Montgomery-Asberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression Scale ( CGI ) were used . Cognitive functions were assessed with the Mini-Mental-State Examination ( MMSE ) and the S and oz Clinical Assessment Geriatric Scale ( SCAG ) . The results showed a comparable reduction in the depression rating scales between the two treatment groups after 6 weeks . However , there was a statistically significant difference ( p < 0.05 ) in HAMD , MADRS , SCAG , MMSE and cognitive subscales of HAMD and SCAG at week 3 in favour of paroxetine , which even was seen after 6 weeks in the SCAG . There were no significant differences between the treatment groups and the number of adverse events reported or in overall tolerability Objective : This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice . Methods : In this double-blind , multicentre study conducted in the general practice , patients with depression ( Montgomery Asberg Depression Rating Scale [ MADRS ] score ≥ 20 ) who were regarded as requiring antidepressant therapy were r and omly assigned to receive paroxetine ( 20 mg , n=184 ) or amitriptyline ( 50–100 mg , n=191 ) once daily for 9 weeks . Results : More patients completed treatment with paroxetine than with amitriptyline ( 71.1 % vs 56.1 % , p=0.009 ) . Depression rating scores ( MADRS and Clinical Global Impression [ CGI ] ) were improved with both agents , but at week 9 , paroxetine achieved more favourable scores compared with amitriptyline on MADRS ( p=0.019 ) , CGI severity of depression ( p=0.044 ) , and CGI efficacy index ( p=0.038 ) . Conclusions : Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline ABSTRACT Objective : This r and omised , double-blind , fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder ( MDD ) . Research design and methods : Patients with a primary diagnosis of MDD and baseline Montgomery-Åsberg Depression Rating Scale ( MADRS ) ≥ 30 were r and omised to 24 weeks of double-blind treatment with fixed doses of either escitalopram ( 20 mg ) ( n = 232 )  or paroxetine ( 40 mg ) ( n = 227 ) . The primary analysis of efficacy was an analysis of covariance ( ANCOVA ) of change from baseline to endpoint ( Week 24 ) in MADRS total score ( last observation carried forward , LOCF ) . Main outcome measures ; results : At endpoint ( 24 weeks ) , the mean change from baseline in MADRS total score was –25.2 for patients treated with escitalopram ( n = 228 ) and –23.1 for patients with paroxetine ( n = 223 ) , result ing in a difference of 2.1 points ( p < 0.05 ) . The difference in the change in the MADRS total score ( LOCF ) was significantly in favour of escitalopram from Week 8 onwards . The proportion of remitters ( MADRS ≤ 12 ) after 24 weeks was 75 % for escitalopram and 67 % for paroxetine ( p < 0.05 ) . The results on the primary efficacy scale were supported by significantly greater differences in favour of escitalopram on the Hamilton Anxiety , Hamilton Depression and Clinical Global Impression-Improvement and -Severity scales . For very severely depressed patients ( baseline MADRS ≥ 35 ) , there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram ( p < 0.05 ) . The overall withdrawal rate for patients treated with escitalopram ( 19 % ) was significantly lower than with paroxetine ( 32 % ) ( p < 0.01 ) . The withdrawal rate due to adverse events was significantly lower for escitalopram ( 8 % ) compared to paroxetine ( 16 % ) ( p < 0.05 ) . There were no significant differences in the incidence of individual adverse events during treatment . Conclusion : Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients BACKGROUND A large proportion of the elderly population complains of depressive symptoms . The ideal antidepressant for these patients , who often suffer from numerous concomitant diseases , should not worsen their cognitive functions and should be free of contraindications . METHOD To assess the effects of 2 selective serotonin reuptake inhibitors on cognitive functions in elderly depressed patients ( ICD-10 criteria ) , we conducted a double-blind , r and omized , parallel-group , multicenter study comparing paroxetine ( 20 - 40 mg daily ) and fluoxetine ( 20 - 60 mg daily ) treatment for 1 year . Cognitive performance was evaluated by means of the  Buschke Selective Reminding Test  , the  Blessed Information and Memory Test  , the  Clifton Assessment Schedule  , the  Cancellation Task Test  , and the  Wechsler Paired Word Test ;  the  Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Anxiety Scale were administered to assess the course of depressive and anxiety symptoms , respectively . RESULTS 242 patients were enrolled ( mean + /- SD age = 75.4 + /- 6.6 years ) . During the study , no deterioration of cognition was observed ; on the contrary , most of the tested cognitive functions improved . Good antidepressant efficacy was maintained for over 1 year with both drugs , based on the percentage of responders to treatment ( patients achieving a HAM-D total score < 10 ; 60 % ) . Both drugs showed a good tolerability and safety profile . CONCLUSION The 2 antidepressants proved to be suitable for the long-term treatment of depression in the elderly and to be devoid of detrimental effects on the tested cognitive functions This study assessed whether fluoxetine , sertraline , and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes . Patients ( N = 284 ) with DSM-IV major depressive disorder were r and omly assigned in a double-blind fashion to fluoxetine , paroxetine , or sertraline for 10 to 16 weeks of treatment . Using the Hamilton Rating Scale for Depression ( HAM-D ) sleep disturbance factor score , patients were categorized into low ( < 4 ) or high ( ≥4 ) baseline insomnia subgroups . Changes in depression and insomnia were assessed . Safety assessment s included treatment-emergent adverse events ( AEs ) , reasons for discontinuation , and AEs leading to discontinuation . In addition , AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation . Depression improvement , assessed with the HAM-D-17 total score , was similar among treatments in all patients ( p = 0.365 ) and the high ( p = 0.853 ) and low insomnia ( p = 0.415 ) subgroups . Insomnia improvement , assessed with the HAM-D sleep disturbance factor score , was similar among treatments in all patients ( p = 0.868 ) and in the high ( p = 0.852 ) and low insomnia ( p = 0.982 ) subgroups . Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening , any worsening , worsening at endpoint , or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup . Treatments were well tolerated in most patients . No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups . These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine , sertraline , and paroxetine in major depressive disorder patients . Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia The present study aim ed to compare the effects of two currently used selective serotonin reuptake inhibitors ( SSRIs ) in Japan taking the individual background in 5-HTT gene-linked polymorphic region ( 5HTTLPR ) genotype into account . Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression . Patients with the l allele had a greater percentage reduction on the total score ( P=0.059 ) and somatic anxiety items ( P=0.026 ) of the 21-item Hamilton Depression Rating Scale ( HAM-D ) score compared to s/s genotype carriers . Paroxetine was significantly more effective than fluvoxamine in the s/s carriers , as evaluated on the percentage reduction in total score ( P=0.012 ) and core ( P=0.049 ) HAM-D after 4 weeks of medication , but not in the l/s carriers . These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs , and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness . We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS ( CDC stages 2B , 2C , 3B , or 3C ) in a 6 week open-label trial with sertraline , paroxetine , or fluoxetine , to assess their effectiveness and tolerability . We further assessed whether treatment of depression result ed in a reduction in both affective and somatic symptoms in this medically ill population . Twenty-four subjects ( 73 % ) completed the trial ( 7 on sertraline , 7 on paroxetine , 10 on fluoxetine ) , 20 ( 83 % ) of whom were clinical responders . Nine dropped out within 1 - 3 weeks of treatment because of adverse effects , mostly agitation , anxiety , and insomnia . Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms , many of the latter having been attributed to HIV rather than depression . These results suggest that , even in later stages of HIV illness , the contribution of depression to perceived somatic symptoms may be significant , and that these symptoms may improve with antidepressant treatment 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 Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors . The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine . However , most data were collected in sample s of out patients . To overcome this restriction , a six-week double-blind control-group study , comparing 30 mg paroxetine with 150 mg amitriptyline per day , was performed in a sample of in patients suffering from major depression . Generally speaking , the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline , either with respect to the total score on the Hamilton Depression Scale ( HAMD ) and the Clinical Global Impressions or with respect to the subscores of the HAMD . One exception was the retardation subscore , in which amitriptyline showed a greater degree of reduction . Both drugs had a characteristic side-effect profile .  Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea BACKGROUND We assessed the therapeutic effects of venlafaxine XR and paroxetine on mood and anxiety symptoms derived from the tripartite model of mood . We hypothesized that the two antidepressants would have largely similar effects on symptoms of negative affect because both agents influence serotonergic systems . However , based on evidence indicating linkages between catecholaminergic activity and the emotional dimension of positive affect , we hypothesized that the catecholaminergic effects of venlafaxine XR would yield particularly pronounced effects on symptoms of positive affect . METHODS Twenty depressed out patients were r and omly assigned to treatment with either venlafaxine XR ( 225 mg/day ) or paroxetine ( 30 mg/day ) during a 12-week treatment trial . Weekly mood ratings were collected using the Mood and Anxiety Symptom Question naire [ Watson , D. , Clark , L.A. , Weber , K. , Assenheimer , J.S. , Strauss , M.E. , McCormick , R.A. , 1995 . Testing a tripartite model : II . Exploring the symptom structure of anxiety and depression in student , adult , and patient sample s. J. Abnorm . Psychol . 104 ( 1 ) , 15 - 25 ] [ Watson , D. , Weber , K. , Assenheimer , J.S. , Clark , L.A. , Strauss , M.E. , McCormick , R.A. , 1995 . Testing a tripartite model : I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales . J. Abnorm . Psychol . 104 ( 1 ) , 3 - 14 ] . RESULTS Consistent with predictions , analyses revealed that there were no significant differences between venlafaxine XR and paroxetine on measures of negative affect . However , contrary to predictions , the two medications produced similar changes on measures of positive affect . LIMITATIONS Replication and extension using a larger sample size are m and ated . CONCLUSIONS These preliminary results suggest that two antidepressants that appear to have dissimilar mechanisms of action may nevertheless have similar effects on the positive and negative affective components of depression . Alternatively , paroxetine may have a clinical ly relevant noradrenergic effect at the dose tested Paroxetine ( 30 mg ) , a selective serotonin ( 5-HT ) reuptake inhibitor , was compared in a double-blind trial to amitriptyline ( 150 mg ) in a sample of 40 in patients aged 18 - 65 years who fulfilled Research Diagnostic Criteria for major depression . Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period . Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment ( first 2 days ) and following withdrawal of active medication . Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition . Paroxetine and amitriptyline decreased the amount of REM sleep , a well-known effect of classical antidepressants . Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality This multinational , r and omized , double-blind , flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine .  Tolerability was assessed by monitoring adverse events throughout the study , and discontinuation events during brief treatment interruption and tapered withdrawal . Discontinuation-emergent effects were evaluated in two separate double-blind periods . First , to mimic the consequences of non-compliance , patients were r and omized to one of two treatment interruption periods ( placebo-substitution for 3–5 days ) . Second , patients were r and omized to a 1–2-week tapered withdrawal period r and omly scheduled between weeks 28 and 31 . The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery – Åsberg Depression Rating Scale ( MADRS ) score at week 8 , using the principle of last observation carried forward . A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram ( 10–20 mg/day ) or paroxetine ( 20–40 mg/day ) . Patients who demonstrated evidence of a significant clinical improvement ( Clinical Global Impression – Improvement of 1 or 2 ) at week 8 entered a 19-week , double-blind maintenance period during which they were treated with the same dose they received at week 8 , followed by a 1–2-week tapered withdrawal period . A total of 89 patients ( 28 % ) withdrew during the study ; significantly ( P<0.01 ) more patients withdrew from the paroxetine group ( 34 % ) than from the escitalopram group ( 21 % ) , and significantly ( P<0.05 ) more paroxetine patients withdrew due to lack of efficacy . The mean MADRS total score improved for both treatment groups from baseline to week 8 , with no statistical difference between groups . In severely depressed patients ( baseline MADRS total score ≥30 ) , escitalopram was superior ( P<0.05 ) to paroxetine at week 27 ( end of maintenance treatment ) . There was a high prevalence of sexual dysfunction at baseline : the mean Arizona Sexual Experience Scale ( ASEX ) score was approximately 20 points in both treatment groups . Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period . During taper and cessation of treatment , patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores The efficacy of paroxetine and fluoxetine and their effects on cognitive and behavioural function were compared in a 6 week , double-blind , r and omized study of 106 elderly depressed patients ( aged 61 to 85 years ) .  Antidepressant efficacy was assessed using the Hamilton depression rating scale ( HAMD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) scale . The S and oz Clinical Assessment Geriatric scale ( SCAG ) , the Mini-Mental State Examination ( MMSE ) , and HAMD cognitive factor scores were used to assess cognitive and behavioural function . Paroxetine demonstrated comparable efficacy to fluoxetine in the treatment of elderly depressed patients , but at the end of treatment , there was a significantly higher proportion of responders to paroxetine than to fluoxetine . Both treatments produced improvements in all measures of cognitive and behavioural function , but paroxetine was significantly superior to fluoxetine from Week 3 , indicating a possible early effect . There was no difference between the two agents in either the tolerability or safety of treatment We report results from a multicenter , placebo-controlled , r and omized , double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in out patients with major depression . Across five U.S. sites , 128 out patients ( mean age : 41.3 + /- 12.6 ; 63 men and 65 women ) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994 . All 128 patients completed a 1-week placebo washout period , and were then r and omized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day ( n = 55 ) , fluoxetine up to 80 mg/day ( n = 54 ) , or placebo ( n = 19 ) . Subjects were evaluated weekly for the first 4 weeks , then at weeks 6 , 9 , and 12 with the 21-item HAMD and the Covi Anxiety Scale . There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity , as well as in the degree of depression and anxiety improvement . There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients . In summary , our results , although limited by the lack of a significant difference from placebo in treatment outcome , suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed out patients , as well as similar safety and tolerability profiles A total of 60 patients aged 65 years and over who were suffering from unipolar depression were entered into a double-blind 6-week comparative study of paroxetine and mianserin . Assessment s of efficacy of treatment included the Hamilton Depression Rating Scale . Clinical Global Impression , and the Leeds Sleep Evaluation Question naire . The results showed that the two drug had equal and acceptable clinical efficacy . There was a similar overall incidence of spontaneously reported adverse events , but with clearly different profiles and a suggestion that mianserin was associated with more anticholinergic effects . In terms of sleep , the study provided evidence of a more beneficial effect from paroxetine Depressive illness among the elderly is an important public health concern . However , treatment of the elderly may be complicated by age-related changes in physiology , general medical status , and susceptibility to side effects . There is therefore a need for improved treatment modalities for depressed elderly patients .  Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake . It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants . The authors present the combined data from two similarly design ed comparisons of paroxetine and doxepin in out patients over 60 years of age with major depression . The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression ( HAM-D ) total score , the Montgomery and Asberg Depression Rating Scale ( MADRS ) , and the Hopkins Symptom Checklist ( SCL ) depression factor score .  Paroxetine was significantly superior to doxepin on the Clinical Global Impressions ( CGI ) scale for severity of illness , the HAM-D retardation factor , and the HAM-D depressed mood item .  Doxepin produced significantly more anticholinergic effects , sedation , and confusion . Paroxetine was associated with more reports of nausea and headache . These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly Paroxetine and venlafaxine are potent serotonin transporter ( SERT ) antagonists and weaker norepinephrine transporter ( NET ) antagonists . However , the relative magnitude of effect at each of these sites during treatment is unknown . Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition . Outpatient subjects ( N=86 ) meeting criteria for major depression were enrolled in a multicenter , 8 week , r and omized , double-blind , parallel group , antidepressant treatment study . Subjects were treated by forced-titration of paroxetine CR ( 12.5–75 mg/day ) or venlafaxine XR ( 75–375 mg/day ) over 8 weeks . Blood sample s were collected weekly to estimate transporter inhibition . Both medications produced dose-dependent inhibition of the SERT and NET . Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90 % ( SD 7 ) and 85 % ( SD 10 ) , respectively . Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36 % ( SD 19 ) and 60 % ( SD 13 ) , respectively . The adjusted mean change from baseline ( mean 28.6 ) at week 8 LOCF in MADRS total score was −16.7 ( SE 8.59 ) and −17.3 ( SE 8.99 ) for the paroxetine and venlafaxine-treated patients , respectively . The magnitudes of the antidepressant effects were not significantly different from each other ( 95%CI −3.42 , 4.54 , p=0.784 ) . The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo . NET antagonism has been posited to contribute to the antidepressant effects of these compounds . The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present Even though r and omised controlled trials are the design of choice for evaluating the efficacy of health care interventions , they are not immune to bias that may affect research process and validity of results . In the present paper we discussed how trial quality may be appraised considering both whether a clinical trial is reported in a comprehensive and complete way ( consistently with what had been declared in the study protocol ) , and whether the characteristics of the trial itself are associated with risk of bias A 6-week , double-blind , parallel group study compared the efficacy and tolerability of paroxetine and fluoxetine in 106 depressed geriatric out patients ( age , ≥65 years ) . Patients with an acute major depressive episode were r and omized to receive either paroxetine ( 20 to 40 mg ; N = 54 ) or fluoxetine ( 20 to 60 mg ; N = 52 ) after a 3− to 7-day washout . Efficacy evaluations at weeks 1 , 3 , and 6 used the 21-item Hamilton Rating Scale for Depression ( HAM-D ) . Cognitive function was assessed by use of the  Mini-Mental State Examination ( MMSE ) and the S and oz Clinical Assessment Geriatric Scale ( SCAG ) . Tolerability was assessed by response to a nonleading question concerning adverse events . There were no significant differences between treatments at week 6 on the HAMD total , change from baseline . However , there was a statistically significant difference ( p < 0.05 ) at week 3 in favor of paroxetine . Results from the MMSE and SCAG showed that , during treatment , patients in the paroxetine group were characterized by greater improvement in cognitive function than were those in the fluoxetine group . This result was statistically significant at week 3 for both scales ( p < 0.05 ) . Adverse events occurred most frequently within the gastrointestinal and nervous systems for both drugs , with no significant differences between treatments 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 The aim of the present paper was to compare the efficacy and safety of duloxetine with paroxetine in the acute treatment of major depressive disorder ( MDD ) . In a r and omized , double-blind trial of 8 weeks active treatment , patients with non-psychotic MDD were r and omized to duloxetine 60 mg ( n = 238 ) or paroxetine 20 mg ( n = 240 ) once daily . Efficacy was primarily measured on change in the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) using a non-inferiority test with a margin of 2.2 . Secondary efficacy measures included the HAMD(17 ) subscales , Hamilton Rating Scale for Anxiety , Clinical Global Impressions-Severity , Patient Global Impressions-Improvement , Somatic Symptoms Inventory and Visual Analog Scales ( VAS ) for pain . Safety measures included treatment-emergent adverse events ( TEAE ) , vital signs , weight , laboratory analyses and electrocardiograms . Non-inferiority of duloxetine to paroxetine was demonstrated because the upper bound of the confidence interval for mean difference in HAMD(17 ) change ( 0.71 ) was less than the non-inferiority margin . Secondary efficacy end-points did not differ significantly between treatments with the exception of VAS back pain , where the pooled mean was lower in the duloxetine group ( 17.1 ) compared with the paroxetine group ( 20.3 , P = 0.048 ) . No significant differences were observed in the number of early discontinuations and overall TEAE . However , significantly greater proportions of patients in the duloxetine group experienced nausea and palpitations . No clinical ly relevant changes in laboratory values , vital signs , weight or electrocardiograms were observed with either treatment . The present study verifies the utility of duloxetine as an efficacious and safe treatment for both emotional and physical symptoms of MDD in this predominantly Asian patient sample The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor . In a double-blind 6-week trial , paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression ( DSM-III ) . One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany . Results showed similar efficacy of both drugs after 6 weeks . The differences between groups in Mont-gomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time . Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline ( p < 0.001 ) , whereas agitation and insomnia were registered more often in the paroxetine group . This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed in patients We investigated platelet [14C]serotonin ( 5-HT ) uptake and lysergic acid diethylamide [ N-methyl-3H ] ([3H]LSD)- and phenyl-6′-paroxetine ( [3H]paroxetine ) binding in 30 patients with major depression at baseline and after 6 months of treatment with either paroxetine or sertraline .  The study was of a double-blind design . Baseline data was compared with an age- and gender-matched group of healthy volunteers .  Baseline Vmax was significantly lower in patients than in controls . Bmax for [3H]paroxetine binding were similar in patients and controls , but patients who suffered their first depression had significantly lower Bmax for [3H]paroxetine binding than patients who had suffered multiple depressions . Twenty-three patients ( 76 % ) ( 13 in the paroxetine group and 10 in the sertraline group ) responded to treatment as judged by a 50 % or more reduction in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores after 6 months of treatment . There were no significant differences between the paroxetine and sertraline treated groups . Both paroxetine and sertraline caused a significant reduction in Vmax and a significant increase in Km . There was a strong correlation between Km and plasma drug concentration in patients who experienced their first depression but not in patients who had suffered multiple episodes . Bmax for [3H]paroxetine binding increased after paroxetine treatment while the opposite occurred after sertraline treatment . There was a significant interaction between the impact of drug and earlier depressions . All patients included in the study had been drug free for at least 2 months . Earlier antidepressant treatment may have long withst and ing effects on the serotonin uptake machinery but it can not be excluded that the sensitivity of the uptake mechanism may become more resistant to change in patients with recurrent depressive episodes BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression .  Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % for paroxetine IR , and 8.3 % for placebo . CONCLUSION Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients , including those with chronic depression A r and omized , double‐blind , parallel‐group , 6‐week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine . After a 1‐week placebo wash‐out , patients suffering from DSM‐III major depression and with a score of 18 or more on the 21‐item Hamilton Rating Scale for Depression ( HRSD ) received either paroxetine or fluoxetine . The patients were assessed for efficacy using the HRSD , Montgomery‐Åsberg Depression Rating Scale and Clinical Global Impression ; for tolerability , adverse events were elicited by the use of a non‐leading question and a side effects checklist . The groups of patients were comparable on entry to the study . One hundred patients were recruited into the study , of whom 78 were evaluable for the efficacy analysis .  Paroxetine and fluoxetine showed comparable efficacy at the end of the 6‐week treatment period , but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed . This could suggest an earlier onset of action with paroxetine .  Also , associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3 . Patients on paroxetine reported fewer adverse events than those on fluoxetine . The most commonly reported adverse events were nausea and vomiting in both groups OBJECTIVE The study examined whether paroxetine inhibits the human norepinephrine transporter in addition to the human serotonin ( 5-HT ) transporter in patients with major depressive disorder . METHOD In an open-label , parallel-group , forced-titration study , 52 out patients with DSM-IV major depressive disorder and a baseline Montgomery Asberg Depression Rating Scale score > or = 20 were r and omly assigned to treatment with paroxetine ( to 60 mg/day ) or desipramine ( to 30 mg/day ) in a 3-to-1 ratio , respectively . Norepinephrine and 5-HT transporter function were assayed by using human transporter transfected cells in the presence of serum collected at baseline and the end of each treatment week . Data from 36 patients were analyzed . RESULTS Paroxetine decreased norepinephrine uptake to 73 % of control ( 27 % inhibition ) at an average serum concentration of 100 ng/ml and 57 % of control ( 43 % inhibition ) at 200 ng/ml . Uptake of 5-HT was decreased to less than 15 % ( greater than 85 % inhibition ) of control at these paroxetine concentrations . Desipramine decreased norepinephrine uptake to near maximal 15 % of control ( 85 % inhibition ) at 100 ng/ml . Uptake of 5-HT was decreased to 82 % of control ( 18 % inhibition ) at 100 ng/ml and 49 % of control ( 51 % inhibition ) at 500 ng/ml . CONCLUSIONS Paroxetine , currently classified as a selective 5-HT reuptake inhibitor , can act as a 5-HT/norepinephrine uptake inhibitor in vivo . The clinical significance of this action on norepinephrine uptake is currently unknown , but this action may contribute to the broad therapeutic efficacy of paroxetine in the treatment of depression , panic disorder , social anxiety disorder , posttraumatic stress disorder , and generalized anxiety disorder Brain-derived neurotrophic factor ( BDNF ) is an important member of the neurotrophin family of growth factors , abundant in the brain and periphery . Research ers have reported that serum BDNF levels in drug-free depressed patients are lower than those of healthy controls , and have proposed that these low levels might reflect a failure of neuronal plasticity in depression . In the present study , we investigated the effects of paroxetine , an SSRI , and milnacipran , an SNRI , on serum BDNF levels in depressed patients .  Serum levels of BDNF were measured by ELISA before , 4 weeks , and 8 weeks after the start of treatment with antidepressants . Forty-two patients were r and omly administered  paroxetine ( 21 cases ) or milnacipran ( 21 cases ) . A negative correlation was found between serum BDNF levels and baseline Ham-D scores . The response and remission rates for each drug were not significantly different . Serum BDNF levels in responders were significantly increased 2.6- and 1.8-fold 8 weeks after treatment with paroxetine or milnacipran , respectively . These results suggest that both drugs improve the depressive state by increasing BDNF levels reuptake inhibitors ( SSRIs ) during continuation therapy . This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression , quality of life , and personality outcomes .  Out patients with unipolar major depression ( DSM-III-R ) were r and omly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine ( 20 - 40 mg ) or sertraline ( 50 - 150 mg ) . Assessment s included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression Scale , the Battelle Quality of Life Question naire , and the Structured Clinical Interview for DSM-III-R Personality Disorders screen question naire . One hundred seventy-six patients ( mean age , 43 years ; 64 % female ; baseline MADRS , 30.3 ) were treated with sertraline and 177 patients ( mean age , 42 years ; 71 % female ; MADRS , 30.7 ) with paroxetine .  Antidepressant efficacy during continuation therapy was sustained , with only 2 % of patients receiving sertraline and 9 % of patients receiving paroxetine suffering a relapse . Continuation therapy result ed in a substantial conversion of responders during short-term treatment to full remission : remitter rates increased from 52 % to 80 % for sertraline and from 57 % to 74 % for paroxetine . The improvements in quality of life were related to a reduced depression score .  SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality . A logistic regression analysis identified early response ( 25 % reduction in MADRS scores at week 2 ) as the most important predictor of treatment response , whereas high severity , chronicity , and poor baseline quality of life had no effect . Both treatments were well-tolerated , with sertraline having a somewhat lower side effect profile .  Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy . Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology Substance P ( SP ) belongs to the neurokinin ( NK ) family of neuropeptides and exerts its biological effects via interaction with the NK1 receptor . The SP-NK1 receptor system is one of the best-characterized neurotransmitter pathways in both the central and peripheral nervous systems . It has been postulated that this pathway may have important roles in a variety of central ly regulated pathophysiologic conditions , including depression . In animal models , central injection of SP was associated with a series of anxiety-like behaviors , and this response could be abolished by pretreatment with SP ( NK1 ) receptor antagonists ( SPAs ) . On the basis of these and other encouraging pre clinical results , several clinical trials have examined the potential of SPAs in the treatment of depression . In phase 2 trials , therapy with the SPAs aprepitant ( MK-0869 ) and compound A result ed in improvements in depression and anxiety symptoms that were quantitatively comparable with those seen with selective serotonin reuptake inhibitors ( SSRIs ) and significantly greater than those seen with placebo . These positive results have established a proof of concept that the inhibition of the SP-NK1 receptor pathway may be a potentially useful novel treatment option for management of patients with depression .  The apparent lack of benefit with SPAs versus placebo in subsequent dose-finding studies with aprepitant and compound A is not surprising , considering the fact that the outcomes with an active control ( SSRI ) in these trials were also similar to those observed with placebo . Future trials with SPAs will focus on the identification of appropriate patients and drug regimens and will also define the role of these agents in the treatment of depression A double-blind multicenter r and omized parallel group study comparing paroxetine and maprotiline was carried out in a total of 544 out patients . Included were patients with varying degrees of severity of depressive symptoms who fulfilled modified RDC criteria for either Minor or Major Depression and showed a HAMD-17 score of > or = 13 . No concomitant benzodiazepine treatment was allowed . Duration of treatment was 6 weeks , after an initial wash-out period . Doses were fixed during the first 3 weeks of treatment , patients receiving either 20 mg paroxetine or 100 mg maprotiline daily . An option for dose escalation was provided for insufficient responders after 3 weeks . The weekly assessment s comprised rating of the HAMD-17 , MADRS , BRMS , RDS , HAMA , CAS , and CGI scales and registration of adverse events by non-leading questions . An intention-to-treat and a completer analysis were performed . Response was defined as a HAMD-17 reduction of > or = 50 % or a HAMD-17 score of < or = 9 at the end of the study or at dropout . The treatment groups were comparable according to demographic data . Overall evaluation indicated equieffective and good antidepressant and anxiety-reducing properties for paroxetine and maprotiline .  No persistent significant differences between treatment groups were observed on any assessment instrument . There was no difference in the frequency of observed side-effects , but side-effect profiles were markedly different , as maprotiline patients had more anticholinergic and paroxetine patients more SSRI-typical side-effects INTRODUCTION : Long-term exposure to antidepressants is required to prevent relapses and recurrences in patients with recurrent major depression . Furthermore , a good pharmacological compliance is the key to successful long-term treatment . Since the early phases of a treatment influence long-term compliance and compliance is adversely affected by poorly tolerated treatments , efficacy and tolerability of paroxetine and amitryptiline over 12 weeks were compared as an introduction to the issue of long-term compliance to these two agents . METHOD : A 12-week , r and omized , double-blind , doubledummy , parallel-group trial which involved 129 patients with recurrent major depression . RESULTS : Both paroxetine and amitriptyline were effective in controlling the symptoms of depression , as shown by the reduction in HAMD total score and CGI severity-of-illness score at endpoint compared to baseline . There was no statistically or clinical ly significant difference between the two treatments in terms of efficacy . However , marked numerical differences were noted in tolerability : the percentage of patients who reported treatment-emergent adverse experiences was greater in the amitriptyline group ( 40.0 % vs 28.1 % ) . This difference was mainly due to anticholinergic adverse events , which were six times more frequent with amitriptyline than with paroxetine . CONCLUSION : When compared with amitriptyline , paroxetine should allow patients with recurrent major depression to receive an equally effective treatment with a relatively lower incidence of adverse experiences Unidimensional subscales for assessment of  major depression  may be more sensitive to antidepressant drug effects than the Hamilton Depression Rating Scale ( HAM-D ) . To further examine this possibility , we analyzed pooled data from eight comparable , well-controlled clinical trials of venlafaxine  and compared such subscales and the 17-item HAM-D ( HAM-D(17 ) ) based on effect size and number of patients required for 80 % power . Symptoms of depression were assessed using the HAM-D among intent-to-treat patients ( 2045 ) r and omly assigned to receive venlafaxine ( immediate release , n = 474 ; extended release , n = 377 ) , one of several selective serotonin reuptake inhibitors ( SSRIs ) ( n = 748 ) , or placebo ( n = 446 ) for up to 8 weeks . With SSRIs or venlafaxine vs. placebo , subscales yielded effect sizes ( 0.328 - 0.528 ) 16 to 76 % larger than the HAM-D(17 ) did ( 0.237 and 0.396 , respectively ) , and required 31 to 64 % fewer patients for 80 % power . With venlafaxine vs. SSRIs , the subscales showed no advantage over the HAM-D(17 ) ; all devices yielded comparable , positive effect sizes ( 0.183 - 0.195 ) . Final subscale scores significantly predicted ( all P < 0.05 ) whether patients met criteria for remission ( eg , HAM-D(17 ) score of < or = 7 ) . These findings suggest that unidimensional subscales are more sensitive to antidepressant drug effects than the HAM-D(17 ) is , but only in active agent/placebo comparisons . Our data further suggest the subscales can predict the presence of remission . Given these findings , prudent use of these subscales may be appropriate , cost-effective , and informative BACKGROUND The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine . METHOD 275 out patients with a diagnosis of major depressive episode ( DSM-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 15 - 45 mg/day ) or paroxetine ( 20 - 40 mg/day ) . Efficacy was assessed by the HAM-D-17 , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scales ( Severity and Improvement ) , and analyses were performed on the intent-to-treat sample ( 127 mirtazapine-treated patients and 123 paroxetine-treated patients ) . RESULTS Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine . Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out . Both drugs were equally effective in reducing symptoms of depression . At week 1 , the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients ( 16.5 vs. 18.8 , p = .0032 ) . Similarly , significantly more mirtazapine-treated patients were HAM-D-17 responders ( > or = 50 % decrease from baseline ) at weeks 1 ( 23.2 % vs. 8.9 % , p = .002 ) and 4 ( 58.3 % vs. 44.5 % , p = .04 ) . Both treatments were equally effective in reducing anxiety . However , the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 ( -5.1 vs. -3.5 , p = .0435 ) . Tolerability of both treatments was good , with more nausea , vomiting , tremor , and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group . CONCLUSION Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated . A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression In this study , we tested the influence of the serotonin type 2A , 3A and 3B receptor genes ( HTR2A , HTR3A , HTR3B ) in addition to a polymorphism in the promoter region of the serotonin transporter ( SERTPR ) , and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine . A total of 100 Japanese patients affected by major recurrent depression were enrolled in a r and omized 6-week study . The clinical response was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) , and adverse drug reactions were assessed at each visit . Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers ( p = 0.015–0.042 ) , more significantly to fluvoxamine . The –1438G/G genotype of HTR2A was associated with a good response to SSRIs ( p = 0.010–0.039 ) , especially to fluvoxamine , and significantly with severe nausea in paroxetine-treated patients ( p = 0.013 ) . The 178C/C genotype of the HTR3A was associated with an antidepressant response ( p = 0.022–0.042 ) , and more significantly in paroxetine-treated patients ( p = 0.002–0.042 ) . These effects were independent of one another . We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs . We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy , and the HTR2A polymorphism is also associated with adverse drug reactions . Furthermore , the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI The combined serotonin – norepinephrine reuptake inhibitor , venlafaxine XR , has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale ( HAM-D ) . This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR , the selective serotonin reuptake inhibitors ( SSRIs ) fluoxetine or paroxetine , or placebo .  Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed . Three treatment groups were compared : venlafaxine XR ( n=560 ) , fluoxetine/paroxetine ( n=298 ) and placebo ( n=496 ) . Mean treatment duration was 8 weeks . Responders were defined as those patients whose HAM-D-21 score decreased by ≥50 % from baseline . Remission was defined as a HAM-D-17 score ≤7 . Sustained remission was defined as maintenance of remission through week 8 or the end of treatment ( if before week 8) and for ≥2 weeks . Between-group rate comparisons in outcome measures were carried out using Fisher 's exact and log-rank tests . Venlafaxine XR produced significantly higher rates of sustained remission in depressed patients compared to fluoxetine/paroxetine or placebo over this 8-week treatment period . As early as week 2 , a significantly greater proportion of patients treated with venlafaxine  achieved improved depression scores ( remission and response ) . A significantly greater rate of remission and sustained remission  occurred with venlafaxine compared to placebo  . Remission was achieved earlier with venlafaxine and lasted throughout the remainder of the study . These results demonstrate that venlafaxine XR is more effective than fluoxetine/paroxetine for sustaining remission of depressive symptoms OBJECTIVES To compare the efficacy of paroxetine and imipramine prospect ively in patients with coexisting depression and dementia . METHODS An 8-week , double-blind , parallel group trial comparing paroxetine 20 - 40 mg/day with imipramine 50 - 100 mg/day in 198 patients aged 60 years or over with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score > or = 20 and a Folstein mini-mental state evaluation score of 17 - 23 points after a 3- to 7-day placebo run-in period . RESULTS Both paroxetine and imipramine reduced the MADRS and the Clinical Global Impression ( CGI ) severity-of-illness and global improvement scores at weeks 2 , 4 , 8 and at endpoint , with no significant differences between treatment groups at any timepoint ( MADRS , p > or = 0.368 ; cgi , p > or = 0.286 ) . There was a statistically significant difference in favour of paroxetine at both the week 4 and week 8 timepoints ( analysis of variance , p < or = 0.049 ) in the Cornell scale for depression in dementia : at endpoint there was no significant difference between treatments ( p = 0.103 ) . Treatment-emergent adverse experiences were reported by 51.5 % ( 51/99 ) of patients treated with paroxetine and 50.5 % ( 50/99 ) of patients treated with imipramine .  Anticholinergic adverse experiences ( paroxetine 6.1 % ; imipramine 13.1 % ) and serious non-fatal adverse experiences ( paroxetine 4.0 % ; imipramine 8.1 % ) were reported by more patients in the imipramine group than in the paroxetine group . CONCLUSIONS Paroxetine and imipramine were both effective in the treatment of depression in elderly subjects with co-existing dementia , and no significant differences were detected between the groups . There were trends suggesting that paroxetine was better tolerated than imipramine in terms of anticholinergic adverse experiences and serious non-fatal adverse experiences BACKGROUND Sexual dysfunction commonly occurs during  antidepressant treatment .  However , the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature . The objectives of this study were ( 1 ) to estimate the prevalence of  sexual dysfunction among patients taking newer antidepressants ( bupropion immediate release [ IR ] , bupropion sustained release [ SR ] , citalopram , fluoxetine , mirtazapine , nefazodone , paroxetine , sertraline , venlafaxine , and venlafaxine extended release [ XR ] )  and ( 2 ) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction . METHOD This cross-sectional , observational study was conducted in 1101 U.S. primary care clinics . Adult out patients ( 4534 women and 1763 men ) receiving antidepressant monotherapy were enrolled . The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Question naire . RESULTS In the overall population , bupropion IR ( 22 % ) and SR ( 25 % ) and nefazodone ( 28 % ) were associated with the lowest risk for sexual dysfunction , whereas selective serotonin reuptake inhibitor ( SSRI ) antidepressants , mirtazapine , and venlafaxine XR were associated with higher rates ( 36%-43 % ) . In a prospect ively defined sub population unlikely to have predisposing factors for sexual dysfunction , the prevalence of sexual dysfunction ranged from 7 % to 30 % , with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR . Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction . CONCLUSION Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a vali date d rating scale . Overall , SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone . Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians , greater recognition and education are imperative when prescribing antidepressant treatment In view of the fact that controlled prospect i ve studies on the benefits of dose escalation of the selective serotonin re‐uptake inhibitor ( SSRI ) paroxetine are lacking , we conducted a double‐blind , r and omized , parallel‐group multicentre study design ed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria ( RDC ) with inadequate treatment response . The study sample consisted of 544 out‐ patients with different degrees of severity of depression . Patients received either 20 mg paroxetine ( n=271 ) or 100 mg maprotiline ( n=273 ) for the first 3 weeks in a double‐blind manner . Response after 3 weeks was defined using explicit operationalized criteria . Patients with inadequate treatment response ( paroxetine group , n=86 ; maprotiline group , n=88 ) were again r and omized to either continuation of the previous dosage ( paroxetine , n=36 ; maprotiline , n=48 ) or increased doses , i.e. 40 mg paroxetine ( n=50 ) or 150 mg maprotiline ( n=40 ) , respectively . Intention‐to‐treat and completer analyses were performed . Defining response as a reduction in Hamilton Depression Rating Scale ( 17‐item version ) ( HAMD‐17 ) score of at least 50 % from baseline , no significant benefits of dose escalation were found for either paroxetine or maprotiline . Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation . After dose escalation , new adverse events that had not been present during treatment with lower doses rarely occurred . Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression With regard to the course of basal human hypothalamus-pituitary-adrenal ( HPA ) system activity , there is a lack of data for comparing different classes of antidepressants . Ninety-four patients were included in a study comparing st and ardized treatment with paroxetine ( PAROX ) and amitriptyline ( AMI ) after a drug-free period of at least 6 days .  Saliva for measurement of cortisol concentrations was obtained daily at 0800 , 1600 , and 2200 during the 6 days of drug-free washout and 35 days of active treatment . The course of HPA system activity and psychopathology , as assessed by the Hamilton Depression Scale , was compared by means of repeated-measurement analyses of variance ( ANOVA-rm ) . Only AMI responders — not PAROX responders or nonresponders to either antidepressant — had a significant decline in saliva cortisol concentrations . In hypercortisolemically depressed patients , treatment with AMI may be preferable to PAROX in order to lower HPA system activity OBJECTIVE To study , whether and how the results from open and double-blind r and omized trials on antidepressants differ . METHODS Seventy-one patients were included in a study comparing open , non-r and omized , st and ardized treatment with paroxetine ( PAROX ) and amitriptyline ( AMI ) after a minimum of six drug-free days ( OPEN ) . A second group of 56 patients received the same treatment under blind-r and omized conditions ( BLIND-R AND OM ) . The course of psychopathology as assessed by the Hamilton Depression Rating Scale was compared using repeated measurements ANOVA-(rm ) . RESULTS While the rate of adverse events was higher in the BLIND-R AND OM compared to the OPEN condition , completer-analyses revealed no differences in psychopathological outcome . CONCLUSIONS With similar clinical outcome BLIND-R AND OM trials of antidepressants may expose depressed patients to an increased risk of adverse events , when compared to OPEN conditions . However , the clinical outcome in study completers did not differ between the BLIND-R AND OM and the OPEN condition . Thus , the psychiatrist 's choice may have impact on adverse events rather than on clinical outcome of antidepressant treatment Objective : The primary objective was to evaluate sexual function ( SF ) separately in men and women with major depressive disorder ( MDD ) before and during treatment with bupropion sustained release ( SR ) or paroxetine .  The secondary objectives involved a comparative evaluation of the Sex Effects Scale ( Sex FX ) and the Investigator-Rated Sexual Desire and Functioning Scale ( IRSD-F ) , as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time . Method : There were 141 patients ( 68 women and 73 men ) who met DSM-IV criteria for a current major depressive episode . They were r and omly assigned to receive bupropion SR ( 150 to 300 mg daily ) or paroxetine ( 20 to 40 mg daily ) under double-blind trial conditions . Patients were assessed at baseline and at 2 , 4 , 6 , and 8 weeks with the 17-item Hamilton Depression Rating Scale ( HDRS17 ) , Sex FX , and IRSD-F. Results : Prior to treatment , women reported significantly lower SF on both the Sex FX and IRSD-F scales , compared with men . During treatment , there were no significant drug differences on measures of SF over time for women ; however , men who were treated with paroxetine reported a worsening of SF , whereas bupropion SR did not significantly alter SF . Both bupropion SR and paroxetine produced clinical ly and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission . There was a statistically significant correlation between the 2 measures of SF at all visits . There was also a significant inverse relation between depression and SF in women , but not in men , irrespective of drug . Conclusion : According to the Sex FX scale , a significant difference in antidepressant-related sexual dysfunction was detected in men , but not women , during treatment with bupropion SR or paroxetine The effects of treatment with serotonin ( 5-HT ) reuptake inhibitors on platelet 5-HT2 receptors , 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors ( SSRI ) , paroxetine , and fluoxetine , for the treatment of major depression . Hamilton Depression Rating Scale ( HAM-D ) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline , after 4 and 8 weeks of treatment , and were compared to 21 healthy controls . Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites , labelled with [3H]paroxetine , or 5-HT2 receptors , labelled with [3H]LSD . However , a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline . A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls . Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively . These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation . Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy , particularly in suicidal depressed patients This multi-centre , double-blind study , carried out in France , was design ed to compare the efficacy and tolerability of paroxetine and clomipramine in elderly patients , aged 60 or above , with reactive depression according to Feighner 's criteria . Patients were r and omly allocated to treatment with either paroxetine ( 20 mg o.d . ) , 41 patients , or clomipramine ( increasing from 20 mg o.d . to 20 mg tds ) , 42 patients , for 5 weeks . Placebo tablets were used to maintain blinding . The degree of depression was determined using the Montgomery-Asberg and the Zung self-rating scales , and also assessed on a visual analogue scale . After 5 weeks of treatment both treatment groups showed a similar degree of improvement on all rating scales . There were no significant differences between the groups . Adverse events occurred in 26 and 28 patients in the paroxetine and clomipramine groups , respectively . In the paroxetine group , many of the events were typical of the gastrointestinal side-effects associated with 5-HT uptake inhibitor therapy . Patients receiving clomipramine experienced events of the type commonly reported with tricyclic antidepressants . There were no significant differences between the groups for either total number of events or for number of patients with specific events . Clinical and laboratory monitoring showed that both drugs were well tolerated Objective : This study was performed to compare the clinical efficacy , side effects , and safety of paroxetine and maprotiline , the latter being the most frequently prescribed antidepressant in Switzerl and . Method : Seventy-one patients ( in and out patients ) with major depression were r and omly allocated to treatment with paroxetine ( 20 to 40 mg daily ) or with maprotiline ( 50 to 150 mg daily ) . Efficacy was measured by means of the Hamilton Psychiatric Rating Scale for Depression , the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impression , and the Hopkins Symptom Checklist . Results : The 2 components showed a similar efficacy . The adverse effect profile was comparable in the 2 treatment groups , although the findings showed a nonsignificant trend pointing in the direction of lower side effects with paroxetine . Conclusion : In the moderate dose regimens tested , the 2 components seemed to be of similar efficacy , with comparable profiles of side effects and safety Paroxetine is a novel phenylpiperidine antide-pressant agent that acts as a potent and selective inhibitor of serotonin reuptake . We report results of a 6-week , r and omized , double-blind , multicenter study comparing paroxetine and fluoxetine in the treatment of major depression . One hundred seventy-eight in patients , who met DSM-III-R criteria for a major depressive episode and had a Montgomery Asberg Depression Rating Scale ( MADRS ) score of 24 or more , were included in the study . Their ages ranged from 18 to 65 years . Subjects were r and omized to receive either paroxetine or fluoxetine for 6 weeks . A 20-mg fixed dose , given once daily in the morning , was used for both drugs . After baseline , regular assessment s were made at the end of weeks 1,2,3,4 , and 6 . Efficacy measures included the MADRS , the Clinical Global Impression severity of illness scale , the Hamilton Rating Scale for Anxiety , the Hospital Anxiety and Depression scale , and the Visual Analogue Scale for anxiety . Safety and tolerability were assessed by adverse event reports , clinical examinations , vital signs , and laboratory data . A marked antidepressant response and good tolerability were seen with both drugs . These results further support the usefulness of paroxetine in the treatment of depressive illness BACKGROUND 60%-90 % of patients with a primary diagnosis of depression also experience symptoms of anxiety , and such patients have a poorer prognosis than those with uncomplicated depression . The serotonin selective reuptake inhibitors have demonstrated efficacy in the treatment of both depression and certain anxiety states . Furthermore , in a meta analysis of the paroxetine clinical trial data base of 2963 patients in whom depression predominated , there was a concomitant reduction in the Hamilton Rating Scale for Depression anxiety factor . The purpose of the present study was to prospect ively compare the efficacy of paroxetine and clomipramine in patients specifically selected for coexisting depression and anxiety . METHOD This was a 12-week , double-blind , parallel-group trial comparing paroxetine 20 - 40 mg/day with clomipramine 75 - 150 mg/day in 1002 patients with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score > or = 20 and a Clinical Anxiety Score ( CAS ) > or = 11 after a 3 - 7 day placebo run-in period . RESULTS Both paroxetine and clomipramine reduced the MADRS and CAS ratings at 2 , 6 , and 12 weeks and at endpoint , with no significant differences between treatment groups at any time point . CGI severity of illness and global improvement ratings were also similar throughout the trial ; however , there was a statistically significant difference in the CGI efficacy index at 6 weeks and at endpoint , favoring paroxetine ( p = .015 and p = .015 , respectively ) . Paroxetine result ed in fewer treatment-emergent adverse experiences and related withdrawals than clomipramine ( p = .025 and p = .008 , respectively ) . The number of serious adverse experiences was not significantly different in the paroxetine group compared with the clomipramine group ( 14 [ 2.8 % ] vs. 27 [ 5.4 % ] ) , but did approach statistical significance ( p = .056 ) . Anticholinergic-emergent adverse experiences were reported twice as frequently by patients in the clomipramine group as in the paroxetine group ( 36.1 % vs. 18.6 % ) . CONCLUSION There was no evidence of any significant difference in efficacy between paroxetine and clomipramine in patients with coexisting depression and anxiety . However , paroxetine was better tolerated as shown by total treatment-emergent adverse experiences , anticholinergic adverse experiences , and withdrawals due to adverse experiences Agomelatine ( S 20098 ) has a unique and new pharmacological profile . It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors , and has been shown to be active in several animal models of depression . The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder ( DSM-IV criteria ) . The methodology used was a conventional double-blind design comparing three different doses of agomelatine ( 1 , 5 and 25 mg once a day ) with placebo over an 8-week treatment period . Paroxetine was used as the study validator . Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were included . On the pivotal analysis , the mean final HAM-D total score ( Full Analysis Set LOCF ) demonstrated agomelatine 25 mg to be statistically more effective than placebo . This was confirmed by other analyses and criteria ( responders , remission , sub population of severely depressed patients , Montgomery – Åsberg Depression Rating Scale , Clinical Global Impression-Severity of Illness ) . Agomelatine 25 mg alleviated the anxiety associated with depression , as measured on Hamilton Anxiety Scale .  Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to vali date the study methodology and population . Agomelatine , whatever the dose , showed good acceptability with a side-effects profile close to that of placebo . In conclusion , this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose Abstract Objective : This study was performed to compare the efficacy and safety of tianeptine and paroxetine in the treatment of major depression . Anxiolytic drug use was systematic ally reported to provide an indirect evaluation of the anxiolytic activity of both treatments . Zopiclone use was assessed to provide an indirect evaluation of the possible hypnotic activity of both treatments . Design and Setting : This was a 3-month controlled , r and omised , double-blind clinical trial which involved 82 centres in France . Patients x : 277 out patients who met DSM-IV criteria for major depression . Interventions : Patients were treated with either tianeptine ( 12.5 mg three times daily ) or paroxetine ( 20 mg once daily plus two placebo capsules ) . The drug dosages could be doubled after 3 weeks if required by the patient ’s medical state . Main Outcome Measures and Results : There was a significant decrease in the Montgomery-Åsberg Depression Rating Scale score in both groups ( from 28.9 at baseline to 11 at endpoint in the tianeptine group , and from 29.6 to 11.6 in the paroxetine group ) after 3 months of treatment . No significant difference was evident between the groups . Secondary criteria confirmed the antidepressant efficacy of both medications , with no difference between tianeptine and paroxetine  ( Hamilton Depression Rating Scale global score at endpoint , Clinical Global Impression final scores , number of responders , delay-to-response , rate of dosage doubling at day 21 ) . The anxiolytic and hypnotic consumption rates decreased in both groups , with no significant difference between the groups . There was no significant difference in clinical safety parameters . Conclusion : Tianeptine appears to be as effective and as safe as paroxetine for the ambulatory treatment of major depression BACKGROUND Fluvoxamine and paroxetine , both serotonin selective reuptake inhibitors ( SSRIs ) , were compared at two centers in a 7-week double-blind study in out patients with major depression , diagnosed by DSM-III-R criteria . METHOD Sixty patients were r and omly assigned to receive dosage titrated upward to between 50 - 150 mg/day of fluvoxamine ( N = 30 ) or 20 - 50 mg/day of paroxetine ( N = 30 ) . The mean + /- SD daily dose administered at the last assessment was 102 + /- 44 mg/day for fluvoxamine and 36 + /- 13 mg/day for paroxetine . Sixteen ( 53 % ) fluvoxamine-treated patients and 10 ( 33 % ) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug . Sample size was calculated to provide at least 85 % power at 5 % level of significance to detect at least a 1.00-point difference in mean severity of adverse events , assuming a st and ard deviation of 1.0 . RESULTS Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 + /- 7.3 ( p < .00 ) and 11.5 + /- 7.4 ( p < .00 ) , respectively , in the Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were mostly mild to moderate in severity . The most common events were headache ( N = 17 , 57 % ) , nausea ( N = 14 , 47 % ) , sweating ( N = 10 , 33 % ) , somnolence ( N = 9 , 30 % ) , diarrhea ( N = 9 , 30 % ) , dry mouth ( N = 8 , 27 % ) , dizziness ( N = 8 , 27 % ) , and , among males , impotence ( N = 3 , 21 % ) and ejaculatory abnormality ( N = 3 , 21 % ) in the paroxetine group , and headache ( N = 12 , 40 % ) , somnolence ( N = 12 , 40 % ) , nausea ( N = 11 , 37 % ) , dry mouth ( N = 11 , 37 % ) , insomnia ( N = 9 , 30 % ) , asthenia ( N = 7 , 23 % ) , and dyspepsia ( N = 7 , 23 % ) in the fluvoxamine group . The only statistically significant difference between treatment groups was for sweating ( 33 % paroxetine vs. 10 % fluvoxamine , p = .028 ) . CONCLUSION Observed differences in some side effects , although not statistically significant , indicate that when a patient has difficulty tolerating one SSRI , the clinician may choose to change to a different agent within the same class In a double‐blind clinical study , antidepressant plasma levels , parameters of platelet serotonin ( 5‐HT ) transport ( Km , Vmax and basal platelet 5‐HT content ) and therapeutic response were measured in depressive patients treated with either paroxetine ( 30 mg/day ) or amitriptyline ( 150 mg/day ) for 6 weeks . No correlation could be found between paroxetine  plasma levels and therapeutic outcome after 2 , 4 and 6 weeks of treatment . In contrast to the amitriptyline group , a marked increase in Km from baseline to week 2 was determined in paroxetine‐treated patients , with Km increase being correlated with paroxetine plasma levels at week 2 . However , no significant relationship could be found between 5‐HT transport parameters and any of the outcome measures in either treatment group A total of 151 out patients with endogenous or mixed endogenous and reactive depression were included in a 6‐week double‐blind study , with extension for up to 1 year , in psychiatric practice . The results showed trends in efficacy variables and a statistically significant difference in a benefit‐risk ratio in favour of paroxetine ( Seroxat ® , Paxil ® ) compared with imipramine . Efficacy was largely maintained in both groups during long‐term treatment . The frequency and severity of side effects in paroxetine patients declined markedly from short‐term to long‐term treatment , whereas changes in imipramine patients were less pronounced . Significantly more imipramine patients gained weight during long‐term treatment . In conclusion , paroxetine is an effective and well tolerated antidepressant , well suited for out patients in psychiatric practice Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability Paroxetine is a selective serotonin uptake inhibitor , which is being investigated as an antidepressant . In this double‐blind , six‐week study 120 out patients with DSM‐I11 major depression were r and omly assigned to treatment with paroxetine , imipramine , or placebo . Results showed a statistically significant superiority of paroxetineover placebo on almost all outcome measures . Paroxetine was significantly superior to imipramine on the HAMD total score and was generally better tolerated than imipramine . The results support paroxetine 's effectiveness in the treatment of major depression and suggest that further studies with this compound are warranted Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor ( SSRI ) . Ninety-one hospitalised patients with a major depression ( DSM-III ) aged 65 and over from six Austrian and one German center were entered into the study , which compared the efficacy and tolerability of paroxetine versus amitriptyline . After 6 weeks both groups showed similarly good therapeutic results . In the paroxetine group , 64.3 % of the patients had a 50 % or more reduction of the HAMD total score compared to 58.1 % in the amitriptyline group . Side effects were distributed similarly in both groups . Patients in the paroxetine group showed a higher incidence of anxiety and agitation ; anticholinergic side effects were registered more often in the amitriptyline group BACKGROUND Depression is a serious and widespread emotional disorder among the elderly . This study compared the efficacy and safety of bupropion sustained release ( SR ) with the selective serotonin reuptake inhibitor paroxetine in the treatment of major depression in elderly out patients . METHOD Elderly ( > or = 60 years ) out patients with major depressive disorder ( DSM-IV criteria ) were evaluated in this 6-week multicenter , r and omized , double-blind study comparing bupropion SR , 100 - 300 mg/day , and paroxetine , 10 - 40 mg/day . Efficacy was assessed by changes in scores on the Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the Clinical Global Impressions-Severity of Illness and -Improvement scales . Safety was assessed by monitoring adverse events , vital signs , and body weight . RESULTS A total of 100 patients ranging in age from 60 to 88 years were r and omly assigned to treatment with bupropion SR ( N = 48 ) or paroxetine ( N = 52 ) . Measurements of efficacy were similar between the 2 treatment groups , with both groups showing improved scores on all depression rating scales . Headache , insomnia , dry mouth , agitation , dizziness , and nausea occurred in > 10 % of patients in both groups ; somnolence , diarrhea , constipation , and anorexia occurred in > 10 % of patients in the paroxetine group . No statistically significant differences between groups in vital signs or weight were found . CONCLUSION Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly . Because of its favorable side effect profile , bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly BACKGROUND Some studies have suggested that selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients . The objective of this study was to compare the 6-week outcome of treatment with nortriptyline and paroxetine in older patients with a major depressive episode . METHOD A double-blind r and omized comparison of nortriptyline and paroxetine was conducted in 80 elderly ( mean + /- SD age = 75.0 + /- 7.4 years ) psychiatric in patients and out patients who presented with a major depressive episode .  Dropout and response rates were compared in patients who began or completed treatment . Rates of response of in patients and patients with melancholic depression were also compared . RESULTS Over 6 weeks , there were no significant differences in dropout rates due to side effects ( nortriptyline , 14 % vs. paroxetine , 19 % ) or for any reason ( 27 % vs. 33 % ) . Similarly , there were no significant differences between the rates of favorable response to nortriptyline or paroxetine ( intent-to-treat analysis , 57 % vs. 44 % ; completer analysis , 78 % vs. 66 % ) . Analyses restricted to in patients or to patients with melancholic depression yielded similar results . CONCLUSION Nortriptyline and paroxetine appear to have similar efficacy and tolerability in the acute ( 6-week ) treatment of older depressed patients , including hospitalized patients and those with melancholic features ABSTRACT — Paroxetine is a new antidepressant drug . It is a potent and selective 5‐HT re‐uptake inhibitor with only weak anticholinergic properties and less effect on the cardiovascular system than the classical tricyclics . In this double‐blind multicenter study the antidepressant effect of paroxetine was compared with mianserin in 70 patients with unipolar or bipolar depression . Each drug was administered for 6 weeks after a 1 week run‐in period at a daily dosage of 30 mg for paroxetine or 60 mg for mianserin .  The 21‐item Hamilton Depression Rating Scale ( HAM‐D ) and the physician 's global assessment were used to assess efficacy . Both treatment groups showed statistically significant improvement of the HAM‐D at Weeks 1 ( base‐line values : paroxetine mean 28.5 ; mianserin mean 30.8 ) through to Week 6 ( paroxetine mean 11.5 ; mianserin mean 17.8 ) ( P < 0.06 ) . The endpoint differences between treatments however were not statistically different ( P= 0.11 ) . The Cleary and Guy factor analysis showed a significant difference ( P < 0.03 ) at Weeks 2 and 4 for cognitive disturbance and at Weeks 4 and 6 for retardation in favour of paroxetine compared with mianserin . Both drugs were well tolerated with nausea and headache in four patients and somnolence in six patients being reported as the most common side‐effect for paroxetine and mianserin respectively The objective of this study was to compare the safety and efficacy of paroxetine with imipramine and placebo in depressed out patients . Following a 4- to 14-day placebo washout , patients were r and omized into treatment groups and received study compound for up to 42 days . At Day 42 , paroxetine was significantly more effective than placebo ( p less than .05 ) in several observer- and patient-rated scales : the Retardation and Anxiety/Somatization factors of the Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Raskin Depression Scale , the Covi Anxiety Scale , the Clinical Global Impressions ( CGI ) Improvement Scale , the Symptom Checklist-56 ( SCL-56 ) Total , and the Patient 's Global Evaluation ( PGE ) . There were no significant differences between paroxetine and imipramine . Significantly more imipramine ( 75 % ) than paroxetine ( 35 % ) or placebo ( 23 % ) patients reported anticholinergic side effects , including blurred vision ( 5 % , 0 % , and 0 % , respectively ) , constipation ( 35 % , 8 % , and 15 % , respectively ) , and dry mouth ( 63 % , 25 % , and 15 % , respectively ) . The data from this study indicated that paroxetine is a safe , well-tolerated , effective treatment for major depressive disorder OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression BACKGROUND Sleep effects of antidepressants are important clinical ly and for elucidating mechanism of action : selective serotonin reuptake inhibitors disturb sleep and 5-HT(2 ) receptor-blocking compounds may enhance sleep quality . AIMS To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression . METHOD Forty patients with depression were r and omised to take paroxetine 20 - 40 mg/day or nefazodone 400 - 600 mg/day for 8 weeks . Objective and subjective quality of sleep and depression measures were assessed throughout . RESULTS Nefazodone significantly increased objective sleep efficiency and total sleep time , and improved subjective sleep on days 3 and 10 . Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8 . Paroxetine but not nefazodone produced marked suppression of rapid eye movement ( REM ) sleep . CONCLUSIONS Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression . These effects are seen within the first 2 weeks of treatment and diminish thereafter This article describes a 6-week study evaluating body sway during double-blind therapy with nortriptyline versus paroxetine in geriatric patients .  Body sway was measured with patients ' eyes open , then closed , using a stable force platform at 4 timepoints : before starting antidepressant medication , and after 1 , 2 , and 6 weeks of treatment . Measures such as the length ( L ) of path of the center of pressure ( COP ) and the area included within the COP path were selected for quantitative assessment of stability . A repeated measures analysis of variance ( ANOVA ) model with planned comparisons was used to examine the pair-wise difference at baseline and Weeks 1 , 2 , and 6 of treatment . No significant difference was found in body sway parameters over the 6 weeks of study for patients treated with either nortriptyline or paroxetine The primary objective of this multicentre , r and omized , double-blind study carried out in France was to compare the efficacy and safety of a 6-week treatment with paroxetine ( 20 mg/day ) or mianserine ( 30 mg/day ) in geriatric hospitalized or ambulatory patients ( > or = 60 years ) treated for a major depressive disorder ( according to DSM III-R ) . A secondary objective was to discriminate those items predicting the response to an agent according to its serotoninergic or noradrenergic pharmacologic profile . The tool used for this latter purpose was the Aubin-Jouvent-Rating-Scale ( AJRS ) which was design ed to assess the deficit of serotonin : this is a scale with 10 items , some of them regrouped into a " general " factor ( irritability , sudden mood change , impatience , aggressivity ) or a " depression " factor ( pain , anxiety , suicidal ideas ) with additional items related to sleep disorders , abnormalities in eating behavior and inability to tolerate isolation . In the perspective of this assessment , paroxetine was chosen due to its potential to inhibit serotonin re-uptake , as compared to mianserin which blocks presynaptic alpha-adrenergic receptors with negligible action on serotonin . This was a multicenter study carried out in France in 50 hospital or private practice psychiatrists . The assessment criteria included the MADRS , the AJRS , the COVI 's anxiety scale , the Folstein 's Mini-mental state ( MMS ) as well as a global assessment by the investigator at the end of the study . Safety was measured with a nondirective question naire , routine laboratory tests as well as a global assessment by the investigator . The primary efficacy criteria was the change in the MADRS global score . Statistical analysis included chi-square or Fisher 's test as well as Student 's and Wilcoxon tests for comparability at baseline , and analysis of variance for the changes in scores as during the study . A total of 116 patients was r and omised ( paroxetine : 54 ; mianserine : 62 ) , of whom 96 completed the study ( paroxetine : 43 ; mianserine : 53 ) . With the exception of MADRS moderately higher in the paroxetine group , both groups were comparable at baseline . After 6 weeks of treatment , a marked improvement was recorded in both groups for all criteria except MMS ; there was a consistent tendency favouring paroxetine which reached statistical significance for the COVI ' scale ( p = 0.001 ) . For a given criterion , the difference paroxetine versus mianserine appeared related to the score at baseline ; it was also more marked in those patients with a AJRS baseline score > or = 20 with a difference for MADRS reduction of marginal significance in favor of paroxetine ( p = 0.061 ) . As regards safety , at least one adverse event was reported in 31.5 % of the patients receiving paroxetine versus 41.9 % in those receiving mianserin ( NS ) ; premature withdrawal related to an adverse event was reported in 11.1 % of the patients in the paroxetine group versus 12.9 % in the mianserin group . No abnormality of clinical significance was reported in either group concerning laboratory tests . In conclusion , this study confirmed the therapeutic value and good safety of paroxetine as an antidepressant in geriatric population s , especially when exist a concomitant anxiety or symptoms likely to reflect a deficit of serotonine ( irritability , emotional lability , restlessness , aggressivity ) and to predict a good response to an agent such as this one ABSTRACT – Paroxetine is a new antidepressant drug with potent serotonin ( 5HT ) uptake inhibitory properties . In this double‐blind comparative study , the antidepressant effect of paroxetine and amitriptyline has been compared in 44 patients with depressive illnesses of an endogenous nature . Each drug was given for 6 weeks . The 17‐item Hamilton Depression Scale was used to measure the antidepressant effect . Reported events were assessed applying a 22‐item check list . Non‐parametric statistical analyses were applied in the evaluation of treatment outcome for the 30 patients who completed the study . The results showed no significant differences in overall antidepressant efficacy between paroxetine and amitriptyline and that paroxetine displayed significantly fewer instances of dry mouth and orthostatic dizziness than amitriptyline . No obvious relationship was demonstrated between the plasma levels of the drugs and their clinical effects Patients and methods Male and female patients diagnosed as having a major episode of depression according to DSM-111 criteria , and who had aminimum score of 18 on the 21-item Hamilton Depression Rating Scale ( HAMD ) , were eligible for entry into the study . Pregnant or lactating women , patients with severe co-existing diseases , known alcohol abusers , and those known to be intolerant of tricyclic antidepressants were excluded Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature , but currently none of them is generally accepted . For the treatment of these conditions , only few recommendations based on empirical data are available . We conducted a r and omized double-blind multicentre study in depressed out patients comparing paroxetine and maprotiline in both patients with minor ( n = 245 ) and major depression ( n = 298 ) . For the diagnosis , Research Diagnostic Criteria were used in a modified version . Two response criteria were applied : a reduction of 50 % or more in total HAMD-17 scores from baseline ( criterion 1 ) , and a reduction of the HAMD-17 total score to 9 points or less ( criterion 2 ) . A completer and an endpoint analysis was performed . For patients with minor depression , remarkably high response rates were found for paroxetine ( criterion 1 : 90.9 % completer , 82.1 % endpoint ; criterion 2 : 89.1 % completer , 82.4 % endpoint ) while the respective rates for maprotiline tended to be lower ( criterion 1 : 80.4 % completer , 71.4 % endpoint ; criterion 2 : 84.9 % completer ; 76.1 % endpoint ) . Response rates in patients with major depression were for paroxetine : criterion 1 : 74.3 % completer , 62.8 % endpoint ; criterion 2 : 76.4 % completer , 65.2 % endpoint ; and for maprotiline : criterion 1:82.4 % completer , 68.5 % endpoint ; criterion 2 : 80.6 % completer ; 66.0 % endpoint , which resembles rates reported from previous antidepressant trials . Both drugs were generally well tolerated . Though no placebo control was carried out , our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine , but also with maprotiline at a favourable risk/benefit ratio 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 Patients and dosage Forty patients who fulfilled the DSM-III criteria of major depressive illness , the severity of which corresponded to at least 18 points on the 21-item Hamilton Depression Rating Scale ( HAMD ) , were entered into the study . The majority suffered from drug-refractory depression : 26 ( 6 5 % ) patients had been treated with antidepressant medication earlier in the current phase , without a satisfactory improvement in any of these patients . After a minimum washout period of three days , the patients were r and omized into two groups of 20 patients each . One group received paroxetine , 30 mg daily as a single dose and the second amitriptyline , 1SOmg daily . Both drugs were given for a period of six weeks BACKGROUND Clinical studies of endogenous concentrations of dehydroepi and rosterone ( DHEA ) and its sulfated conjugate DHEA-S in depression are limited . This study was design ed to evaluate the influence of successful pharmacological treatment of late-life depression on concentrations of DHEA , DHEA-S and cortisol . METHODS We determined endogenous concentrations of DHEA , DHEA-S and cortisol in elderly control subjects ( n = 16 ) and in elderly depressed patients who remitted ( n = 44 ) or failed to remit ( n = 16 ) with pharmacological treatment . Depressed patients were treated for 12 weeks with either nortriptyline or paroxetine . RESULTS In remitters , DHEA and DHEA-S concentrations were lower at week 12 than at week 0 ( p = .002 and p = .0001 , respectively ) . In the nonremitters and control subjects , neither DHEA nor DHEA-S concentrations changed . Decreases in hormone concentrations were associated with improvement in mood and functioning in depressed patients . Although cortisol concentrations decreased in remitters and nonremitters , the change was not significant . CONCLUSIONS Our data suggest that the decrease in DHEA and DHEA-S in remitters is related to remission of depression rather than to a direct drug effect on steroids , as nonremitters had no change in hormone concentrations Paroxetine is a novel antidepressant that selectively inhibits neuronal reuptake of serotonin . Results are reported from a 6-week , double-blind trial of paroxetine , imipramine , and placebo in 120 out patients with DSM-III major depression .  Paroxetine was significantly superior to placebo on almost all measures . This included the main outcome variable , the Hamilton Rating Scale for Depression ( HAM-D ) , and its factor scores , anxiety-somatization , cognitive disturbance , psychomotor retardation , and sleep disturbance . There were no significant differences between paroxetine and imipramine on the same scales . Imipramine-treated patients were significantly more likely than those taking placebo to report one or more adverse effects , which were predominantly anticholinergic in nature . There was no significant difference in the number of paroxetine and placebo patients who reported one or more adverse effects . The results of this and similar studies indicate that paroxetine is an effective treatment in major depression and has a favorable side effect profile CONTEXT Major depressive disorder causes significant morbidity and mortality . Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder . OBJECTIVE To evaluate duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , on improvement of emotional and painful physical symptoms . DESIGN R and omized , double-blind , evaluation of duloxetine at 40 mg/d ( 20 mg twice daily ) and 80 mg/d ( 40 mg twice daily ) versus placebo and paroxetine 20 mg/d in depressed out patients . MAIN OUTCOME MEASURES The primary efficacy measure was the 17-item Hamilton Depression Rating Scale . Visual Analog Scales for pain , Clinical Global Impression of Severity , Patient 's Global Impression of Improvement , and Quality of Life in Depression Scale were also used . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests . RESULTS Duloxetine 80 mg/d was superior to placebo on mean 17-item Hamilton Depression Rating Scale total change by 3.62 points ( 95 % CI 1.38 , 5.86 ; P = 0.002 ) . Duloxetine at 40 mg/d was also significantly superior to placebo by 2.43 points ( 95 % CI 0.19 , 4.66 ; P = 0.034 ) , while paroxetine was not ( 1.51 points ; 95 % CI -0.55 , 3.56 ; P = 0.150 ) . Duloxetine 80 mg/d was superior to placebo for most other measures , including overall pain severity , and was superior to paroxetine on 17-item Hamilton Depression Rating Scale improvement ( by 2.39 points ; 95 % CI 0.14 , 4.65 ; P = 0.037 ) and estimated probability of remission ( 57 % for duloxetine 80 mg/d , 34 % for paroxetine ; P = 0.022 ) . The only adverse event reported significantly more frequently for duloxetine 80 mg/d than for paroxetine was insomnia ( 19.8 % for duloxetine 80 mg/d , 8.0 % for paroxetine ; P = 0.031 ) . Hypertension incidence was not affected by any treatment . CONCLUSION Duloxetine therapy was efficacious for emotional and physical symptoms of depression , with a selective serotonin reuptake inhibitor-like profile of side effects This double-blind study compared initial combination therapy against monotherapy using two antidepressant drugs with complementary mechanisms of action on the serotonin ( 5-HT ) and norepinephrine ( NE ) systems . Sixty one adult patients with a DSM-IV diagnosis of unipolar depression were r and omized to receive mirtazapine ( 30 mg/day ) , paroxetine ( 20 mg/day ) , or the combination of both drugs for 6 weeks . Response at week 4 was defined as a 30 % reduction in the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and at week 6 as a 50 % reduction in the MADRS . Remission was defined as a reduction in the MADRS score to 10 points or less . After 4 weeks , non-responders in the monotherapy groups had their medication dose increased by 50 % . After 6 weeks , non-responders on monotherapy had the second trial drug added to their current regimen . Non-responders on combination therapy had the dosage of both drugs increased by 50 % . There was a significantly greater decrease in MADRS scores in the combination group compared to the monotherapy groups at days 28 , 35 and 42 , with a 10 point difference separating the combination from the monotherapies at day 42 . Remission rates at week 6 were 19 % on mirtazapine , 26 % on paroxetine , and 43 % on the combination . Fifteen patients in the mirtazapine arm and 10 in the paroxetine arm who did not respond had the other drug added to their current regimen , and 5 on the combination had an increase in dose of both drugs secondary to non-response . Of these 30 patients , approximately 50 % went on to achieve remission in the subsequent 2 weeks . These results indicate that the combined use of two antidepressants was well tolerated and produced a greater improvement than monotherapy Results from a single-center , 6-week , double-blind , r and omized prospect i ve study of paroxetine , a selective serotonin reuptake inhibitor ; imipramine ; and placebo are reported . One hundred twenty out patients with a moderate-to-severe DSM-III diagnosis of major depression were r and omly assigned to one of the three treatments following a 4- to 10-day single-blind placebo washout period . Significant differences favoring paroxetine over placebo were present at endpoint on most major efficacy measures .  Paroxetine was also well tolerated ; 5 ( 15 % ) paroxetine and 5 ( 14 % ) placebo patients dropped out of the study due to adverse effects .  Imipramine , however , was comparatively poorly tolerated . Forty-five percent of  imipramine-treated patients ( N = 17 ) dropped out of the study due to adverse effects . None of the efficacy measures showed a significant difference between imipramine and placebo . This finding was probably due to the high number of imipramine patients who discontinued before they could improve . These results support the efficacy of paroxetine in the treatment of major depression and underline its favorable side effect profile compared with tricyclic antidepressants BACKGROUND The effects of extended selective serotonin reuptake inhibitor ( SSRI ) treatment on weight are not well characterized . Also unknown is whether different agents have differential effects . To examine these questions , we assessed weight changes in patients r and omly assigned to long-term treatment with  fluoxetine , sertraline , or paroxetine . METHOD Patients ( N = 284 ) with major depressive disorder ( DSM-IV ) were r and omly assigned to double-blind treatment with fluoxetine ( N = 92 ) , sertraline , ( N = 96 ) , or paroxetine ( N = 96 ) for a total of 26 to 32 weeks . The mean percent change in weight was compared for each group , as was the number of patients who had > or = 7 % weight increase from baseline . RESULTS Patients ( fluoxetine , N = 44 ; sertraline , N = 48 ; paroxetine , N = 47 ) who completed the trial were included in these analyses . Paroxetine-treated patients experienced a significant weight increase , fluoxetine-treated patients had a modest but nonsignificant weight decrease , and patients treated with sertraline had a modest but nonsignificant weight increase . The number of patients whose weight increased > 7 % from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients . CONCLUSION Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used OBJECTIVE Although adverse events are a key factor in compliance , their evolution during treatment with antidepressants is poorly documented . Therefore , the time course of adverse events during 6 months of antidepressant treatment was investigated . METHOD 85 psychiatric out patients with a DSM-IV diagnosis of major depressive disorder ( with the exclusion of other DSM-IV Axis I disorders ) were enrolled between September 2002 and March 2003 in a multicenter , r and omized , double-blind trial with selective serotonin reup-take inhibitors ( fluoxetine [ N = 42 ] and paroxetine [ N = 43 ] ) . At each visit , the presence and severity of treatment-emergent adverse events were assessed systematic ally using the UKU Side Effect Rating Scale ( UKU ) . General linear mixed modeling was used to investigate the predictors of the time course of adverse events . RESULTS Overall , the number of at least moderately severe adverse events decreased with time . More severely depressed patients reported overall more ( at least moderately severe ) adverse events than less severely depressed patients ( p = .0002 ) , but the decrease in reported adverse events was comparable over time . Men ( N = 30 ) and women ( N = 55 ) reported initially the same number of at least moderately severe adverse events , but the habituation was more rapid in men ( p < .0001 ) . Completers ( N = 58 ) and dropouts ( N = 27 ) did not differ initially , but completers ' habituation was more rapid ( p = .014 ) . The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men ( p = .0025 ) . CONCLUSION The time course of adverse events varies with the severity of depression , sex , completer or dropout status , and recurrent versus first-episode depression The efficacy of amisulpride in depressive disorders has been demonstrated in dysthymia and in double depression . Limited data are available in major depression . A r and omized , double-blind , parallel group , multicentre study was set up to compare the efficacy and tolerability of amisulpride ( 50 mg o.d . ) and paroxetine ( 20 mg o.d . ) for 8 weeks in 272 patients with major depression ( DSM-IV and baseline Hamilton Depression Rating Scale ( HAMD ) score ≥18 ) . The study was design ed as a non-inferiority trial based on the proportion of responders ( ≥50 % decrease in HAMD total score ) at end-point , with a maximal allowable difference of 15 % ; secondary end-points included HAMD total and cluster scores , Montgomery and Asberg Depression Rating Scale score and responders rates and Clinical Global Impression improvement . The tolerability evaluation was based on incidence of adverse events and routine laboratory tests . The results did not disclose statistically significant differences between treatments , although the hypothesis of an efficacy difference between the two treatments within the set limit at day 56 could not be accepted . The issue of non-inferiority trials is discussed The effects of an abrupt interruption of agomelatine , a new melatonergic/serotonergic antidepressant , were explored in a double-blind , placebo-controlled study . Paroxetine was used as active control . After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day , sustained remitted depressed patients were r and omized for 2 weeks , under double-blind conditions , to placebo or to their initial antidepressant treatment .  Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms ( DESS ) checklist .  One hundred and ninety-two sustained remitted patients were r and omized to the 2-week discontinuation period . Patients who  discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine . Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms , during the first week , compared to those who continued with paroxetine ( respective mean number of emergent symptoms : 7.3±7.1 and 3.5±4.1 , P<0.001 ) . No significant difference was shown between the continuing and interrupting groups in the second week of discontinuation . By contrast to paroxetine , abrupt cessation of agomelatine is not associated with discontinuation symptoms Objective : The development of the Antidepressant Compliance Question naire ( ADCQ ) , assessing  patients ’ attitudes and beliefs on depression and antidepressants A six-week , double-blind , r and omised study was used to compare the efficacy , tolerability , safety and effect on cognitive function of paroxetine with that of lofepramine in the treatment of 138 patients with major depression in general practice .  Efficacy was assessed using the Montgomery and Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) scale . Effect on cognitive function was assessed using the paired associate learning test and the serial " E ' cancellation test . The results showed that the antidepressant efficacy of paroxetine was comparable to that of lofepramine in the treatment of depressed patients . Similar improvements in mean total MADRS scores were observed in both treatment groups , but a significantly greater improvement was seen in the CGI with paroxetine at weeks 2 and 4 . The effect of treatment on cognitive function did not differ significantly across the two treatment groups , nor did the number of adverse events reported nor the overall tolerability There is some empirical evidence that selective serotonin reuptake inhibitors reduce suicidal ideas faster than other antidepressants . These findings are well in line with the theory of a serotonergic hypofunction in suicidal patients . To test this hypothesis the data of a 6-week double-blind control-group study comparing paroxetine versus amitriptyline were analyzed with respect to suicidality .  The global antidepressive efficacy was comparable under dosages of 30 mg paroxetine or 150 mg amitriptyline per day . A differentiated analysis failed to confirm the hypothesis of a faster reduction of suicidal cognitions by paroxetine Abstract : Depressed patients may exhibit reduced heart rate variability ( HRV ) , and antidepressants which block norepinephrine uptake may also lower HRV . This study compared paroxetine ( PAR ) and venlafaxine XR ( VEN-XR ) on HRV . Out patients were r and omly assigned to double-blind treatment with PAR up to 40 mg or VEN-XR up to 225 mg daily . HRV measures of parasympathetic control consisted of change in R-R interval during forced 10-second breaths and respiratory sinus arrhythmia ( RSA ) during paced breathing . Ex vivo estimates of serotonin and norepinephrine transporter occupancy were obtained before and after treatment , as were measures of depression , anxiety , and resilience . Plasma drug concentrations were measured at end point . Forty-nine patients entered treatment ; 44 of whom were evaluable ( n = 22 per group ) . Significant within-group reductions were noted in R-R interval variation and in RSA after VEN-XR only . Between-group analyses showed significant group-by-time interaction , with greater reduction in R-R interval variation and in RSA for VEN-XR compared with PAR . Improvement in resiliency correlated significantly with norepinephrine transporter occupancy for VEN-XR . Further comparisons of selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor drugs on HRV are warranted Objective To assess the potential economic impact of new and more expensive antidepressants on the overall cost of treatment using cost-effectiveness analysis . Method For this analysis , a computerized decision tree of clinical practice was developed to model the 12-month treatment of moderate to severe depression in Canada . To complete the model , data were obtained from physician panels , the Ontario Ministry of Health , and clinical comparative trials of paroxetine , a selective serotonin reuptake inhibitor , and Imipramine , a tricyclic antidepressant . Results The overall cost of treatment when paroxetine 30 mg per day was used first-line was found to be lower than when generic imipramine was used as the initial therapy ( $ 1697 versus $ 1793 ) . The higher drug cost of paroxetine ( $ 1.69 per day ) versus imipramine ( $ 0.05 per day ) was offset by a higher rate of treatment failures with the tricyclic necessitating an alternate therapy , additional physician visits and /or hospitalization . Sensitivity analysis of key variables determined that drug price and relapse rates after discontinuation were relatively insensitive predictors of the overall cost of care . More important was the continuation rate while on different therapies . Conclusion Paroxetine demonstrated a cost-benefit relative to Imipramine when the continuation rate was ≥ 47 % . Clinical trials of paroxetine have reported continuation rates of 41 % to 65 % , suggesting that paroxetine is a cost-effective alternative to Imipramine in the 1-year management of patients with moderate to severe depression 21 depressed patients of the Basle University Psychiatric Outpatient Clinic were treated in a double-blind study with paroxetine and amitriptyline . 11 of these patients did not continue the trial until the end of the 7th week . There was a significant difference in the number of dropouts between the two groups : 80 % of the amitriptyline group did not continue until the end , while in the paroxetine group we found only 30 % dropouts . The patients of both groups showed a gradual decrease of the median total scores on the Hamilton and the Montgomery and Asberg Depression Rating Scales . Although the number of patients who stayed in the trial for at least 4 weeks ( 8 with paroxetine , 6 with amitriptyline ) is quite small , we see from the results of the clinical global impression that the members of the paroxetine group improved most of all in the somatic symptoms , while considering their moods we found no differences between the groups . Patients of both groups complained about side effects , most of all about dry mouth and tiredness . From the high rate of dropouts under amitriptyline we found that the side effects under this drug were more severe and therefore led to the dropouts Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes
target: We found no clear evidence that paroxetine was more or less effective compared with other antidepressants at increasing response to treatment at acute ( six to 12 weeks ) , early ( one to four weeks ) , or longer term follow-up ( four to six months ) .
  Paroxetine was associated with a lower rate of adverse events than amitriptyline , imipramine and older ADs as a class , but was less well tolerated than agomelatine and hypericum .
  Some possibly clinical ly meaningful differences between paroxetine and other ADs exist , but no definitive conclusions can be drawn from these findings .
  In terms of early response to treatment ( one to four weeks ) there was moderate quality of evidence that mirtazapine was better than paroxetine and that paroxetine was better than reboxetine .
  However there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point .
background: BACKGROUND Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors ( SSRIs ) and has been studied in many r and omised controlled trials ( RCTs ) .
  However , these comparative studies provided contrasting findings and systematic review s of RCTs have always considered the SSRIs as a group , and evidence applicable to this group of drugs might not be applicable to paroxetine alone .
  The present systematic review assessed the efficacy and tolerability profile of paroxetine in comparison with tricyclics ( TCAs ) , SSRIs and newer or non-conventional agents .
  OBJECTIVES 1 .
  To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of Major Depressive Disorder.2  .
  To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.3 .
  To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents .