title: Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. Sertraline Treatment of Co-occurring Alcohol Dependence and Major Depression Paroxetine controlled-release formulation in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled study in Japan and Korea. Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Efficacy of controlled-release paroxetine in the treatment of late-life depression. Low doses of controlled-release paroxetine in the treatment of late-life depression: a randomized, placebo-controlled trial. A comparison of fluoxetine, imipramine, and placebo in patients with major depressive disorder. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression. A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. 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 Escitalopram (10–20 mg/day) is effective and well tolerated in a placebo‐controlled study in depression in primary care Escitalopram in the treatment of depressed elderly patients. 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 An examination of the sensitivity of the six-item Hamilton Rating Scale for Depression in a sample of patients suffering from major depressive disorder. Paroxetine in the treatment of depression: a comparison with imipramine and placebo. A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia The efficacy and safety of paroxetine compared with placebo in outpatients with major depression. Addition of an NK1 receptor antagonist to an SSRI did not enhance the antidepressant effects of SSRI monotherapy: results from a randomized clinical trial in patients with major depressive disorder
abstract: CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy Background : Major depressive disorder occurs commonly in association with alcohol dependence , both in clinical sample s and in the community . Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results . This multicenter , double-blind , placebo-controlled trial of sertraline was design ed to address many of the potential method ological shortcomings of studies of co-occurring disorders . Method : Following a 1-week , single-blind , placebo lead-in period , 328 patients with co-occurring major depressive disorder and alcohol dependence were r and omly assigned to receive 10 weeks of treatment with sertraline ( at a maximum dose of 200 mg/d ) or matching placebo . R and omization was stratified , based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking , result ing in a sample of 189 patients with Hamilton Depression Rating Scale scores ≥17 ( group A ) and 139 patients with Hamilton Depression Rating Scale scores ≤16 ( group B ) . Results : Both depressive symptoms and alcohol consumption decreased substantially over time in both groups . There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients . Conclusion : Despite careful attention to method ological considerations , this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence . The high rate of response among placebo-treated patients may help to explain these findings . Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders AIM The main purpose of this study was to evaluate the efficacy of paroxetine controlled-release ( CR ) formulation compared to placebo . A secondary objective was to test the hypothesis that the CR decreases selective-serotonin-reuptake-inhibitors-induced nausea as its formulation allows more distal gastrointestinal absorption than the paroxetine immediate-release ( IR ) formulation . METHODS We conducted this study in Japanese and Korean patients with major depressive disorder ( MDD ) in order to demonstrate the efficacy and safety of paroxetine CR compared with placebo . The primary efficacy end-point was the adjusted mean change from baseline in the 17-item Hamilton Rating Scale for Depression total score at Week 8 . RESULTS A total of 416 patients with MDD were r and omly assigned to the CR , IR and placebo groups . The mean change from baseline in the 17-item Hamilton Rating Scale for Depression was -12.8 in the CR group , -12.5 in the IR group , and -10.4 in the placebo group , which showed a statistically significant difference compared to placebo in CR ( P < 0.001 ) and IR ( P = 0.015 ) . The incidence of adverse events was 65 % in CR , 69 % in IR and 55 % in placebo . The adverse events were mostly mild or moderate in severity . In the early treatment period , when initiated from 12.5 mg , the incidence of nausea in the CR group was 6 % , which was comparable with that of placebo ( 5 % ) . CONCLUSION Paroxetine CR is efficacious in the acute treatment of MDD and may have the potential benefit of decreasing the incidence of nausea in the early treatment period The efficacy and safety of fluvoxamine maleate , a selective serotonin reuptake inhibitor , was compared with placebo and imipramine in patients with major depressive disorder . Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression ; however , this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine ( 80 - 240 mg/day ) . After a 1- to 2-week , single-blind , placebo washout phase , 150 depressed out patients were r and omized to double-blind treatment with fluvoxamine maleate ( 50 - 150 mg/day ) , imipramine ( 80 - 240 mg/day ) , or placebo for 6 weeks . Fluvoxamine produced a significant therapeutic benefit over placebo ( p < or = 0.05 ) as assessed by the total score on the Hamilton Rating Scale for Depression ; imipramine ( 80 - 240 mg/day ) produced similar results . The secondary outcome variables ( i.e. , Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor ) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study . Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients . As expected from the pharmacology of these agents , the imipramine groups reported more anticholinergic effects ( dry mouth , dizziness , and urinary retention ) and electrocardiographic effects , whereas the fluvoxamine group reported more nausea , somnolence , and abnormal ejaculation . The majority of these adverse events were mild to moderate and , with the exception of dry mouth ( imipramine ) and abnormal ejaculation ( fluvoxamine ) , were transient . The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate ( 50 - 150 mg/day ) as compared with placebo ; it is also as effective as the tricyclic antidepressant imipramine ( 80 - 240 mg/day ) in patients with major depressive disorder OBJECTIVE Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence . While some studies have demonstrated that antidepressants reduce depressive symptoms in individuals with depression and alcohol dependence , most studies have not found antidepressant treatment helpful in reducing excessive drinking in these patients . The authors provide results from a double-blind , placebo-controlled trial that evaluated the efficacy of combining approved medications for depression ( sertraline ) and alcohol dependence ( naltrexone ) in treating patients with both disorders . METHOD A total of 170 depressed alcohol-dependent patients were r and omly assigned to receive 14 weeks of treatment with sertraline ( 200 mg/day [ N=40 ] ) , naltrexone ( 100 mg/day [ N=49 ] ) , the combination of sertraline plus naltrexone ( N=42 ) , or double placebo ( N=39 ) while receiving weekly cognitive-behavioral therapy . RESULTS The sertraline plus naltrexone combination produced a higher alcohol abstinence rate ( 53.7 % ) and demonstrated a longer delay before relapse to heavy drinking ( median delay=98 days ) than the naltrexone ( abstinence rate : 21.3 % ; delay=29 days ) , sertraline ( abstinence rate : 27.5 % ; delay=23 days ) , and placebo ( abstinence rate : 23.1 % ; delay=26 days ) groups . The number of patients in the medication combination group not depressed by the end of treatment ( 83.3 % ) approached significance when compared with patients in the other treatment groups . The serious adverse event rate was 25.9 % , with fewer reported with the medication combination ( 11.9 % ) than the other treatments . CONCLUSIONS More depressed alcohol-dependent patients receiving the sertraline plus naltrexone combination achieved abstinence from alcohol , had delayed relapse to heavy drinking , reported fewer serious adverse events , and tended to not be depressed by the end of treatment 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 OBJECTIVE To evaluate the efficacy and tolerability of low daily doses of controlled-release ( CR ) paroxetine in patients with late-life depression . METHOD This was a 10-week , multicenter , placebo-controlled , double-blind , fixed-dose trial r and omly assigning patients > or= 60 years old to daily doses of paroxetine CR  12.5 mg ( N = 168 ) , paroxetine CR 25 mg ( N = 177 ) , or placebo ( N = 180 ) . Patients had major depressive disorder ( DSM-IV criteria ) and 17-item Hamilton Rating Scale for Depression ( HAM-D ) total scores of > or= 18 . The primary efficacy variable was the change from baseline to study endpoint in total HAM-D scores . The study was conducted from June 2003 to October 2004 . RESULTS The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 ( 95 % CI = -3.41 to -0.19 , p = .029 ) for paroxetine CR 12.5 mg , and -3.3 ( 95 % CI = -4.84 to -1.68 , p < .001 ) for paroxetine CR 25 mg . A significantly larger percentage of patients achieved remission ( HAM-D total score < or= 7 at endpoint ) with paroxetine CR 25 mg ( 41 % ) , but not with 12.5 mg ( 31 % ) , as compared with placebo ( 28 % ) ( p = .008 ) . Both doses of paroxetine CR also achieved statistical significance compared to placebo for the Clinical Global Impressions-Severity of Illness scale ( p < .01 ) and the patient-rated measures of depression severity ( p < .05 ) and quality of life ( p < or= .001 ) . Both active treatments were generally well tolerated , with adverse event withdrawal rates of 6 % , 8 % , and 7 % for paroxetine CR 12.5 mg , paroxetine CR 25 mg , and placebo , respectively . CONCLUSION These data demonstrate that paroxetine CR 12.5 mg and 25 mg daily are efficacious and well tolerated in the treatment of major depressive disorder in patients > or= 60 years of age , although effect sizes are relatively smaller with the 12.5 mg/day dose The efficacy and safety of fluoxetine were compared with those of imipramine and of placebo in a 6-week r and omized double-blind parallel study of patients with major depressive illness .  Mean values for all efficacy measurements were improved over baseline with fluoxetine and imipramine treatment ( p less than .001 ) . More fluoxetine patients completed the study than did  imipramine or placebo patients . Predominant adverse experiences reported by imipramine patients were dry mouth and dizziness/lightheadedness . Predominant adverse experiences reported by fluoxetine patients were drowsiness/sedation and excessive sweating . In a subsequent 48-week open-label study , the predominant adverse experience in the fluoxetine group was excessive sweating and in the imipramine group was still dry mouth . In this study , fluoxetine relieved the symptoms of major depressive illness effectively and significantly better than placebo and was better tolerated than imipramine OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo  took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial 1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients . Twenty-two patients received fluvoxamine ( mean dose 101 mg/day ) , 25 received imipramine ( mean dose 127 mg/day ) and 22 received placebo . 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients , no statistically significant changes in haematology or urinalysis were judged to be medically relevant . Fluvoxamine exhibited fewer anticholinergic side effects than imipramine . 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients , as measured using the Hamilton Rating Scale for Depression , and the Clinical Global Impression Scale . Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4 , but not for fluvoxamine patients . It is postulated on the basis of quantitative pharmaco-EEG findings , that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter BACKGROUND Many antidepressants are associated with  sexual dysfunction  , a side effect that may lead to patients ' dissatisfaction and noncompliance with treatment . OBJECTIVE This study compared the efficacy , tolerability , and effects on sexual functioning of bupropion sustained release ( bupropion SR ) and the selective serotonin reuptake inhibitor fluoxetine . METHODS In this multicenter , r and omized , double-blind , double-dummy , parallel-group study , patients with recurrent major depression were treated with bupropion SR 150 to 400 mg/d , fluoxetine 20 to 60 mg/d , or placebo for up to 8 weeks .  Depression and sexual-functioning status were assessed by site-specific trained investigators at weekly clinic visits ; tolerability was assessed primarily by monitoring adverse events . RESULTS Four hundred fifty-six patients participated in the study , 150 receiving bupropion SR , 154 fluoxetine , and 152 placebo .  The majority of patients in each group completed the study ( 63 % each , bupropion SR [ n = 94 ] and fluoxetine [ n = 97 ] ; 67 % , placebo [ n = 102 ] ) . Bupropion SR and fluoxetine were similarly effective in the treatment of depressive symptoms . Beginning at week 2 and continuing throughout the study , significantly more fluoxetine-treated patients experienced orgasm dysfunction than did patients receiving bupropion SR or placebo ( P < 0.001 ) ; similar results were seen in patients defined as clinical responders ( > or = 50 % decrease from baseline in 21-item Hamilton Rating Scale for Depression [ HAM-D ] total score ) ( P < 0.001 ) and in those experiencing remission of depression ( HAM-D total score < 8) ( P < 0.05 ) . At various time points , worsened sexual functioning , sexual desire disorder , sexual arousal disorder , and dissatisfaction with sexual functioning in those satistied at baseline were more frequently associated with fluoxetine treatment than with bupropion SR or placebo . Both active treatments were well tolerated . CONCLUSIONS Bupropion SR and fluoxetine were similarly effective and well tolerated in the treatment of depression . Fluoxetine , however , was more frequently associated with sexual dysfunction compared with bupropion SR . Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning 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 & NA ; Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference . Patients were r and omized to receive flexible doses of 10–20 mg/day escitalopram ( n=155 ) , 20–40 mg/day citalopram ( n=160 ) , or placebo ( n=154 ) over an 8‐week double‐blind period . The primary efficacy parameter was the change from baseline to last assessment in the Montgomery – Asberg Depression Rating Scale total score . Escitalopram produced a statistically significant therapeutic difference of 2.9 points ( P=0.002 ) compared to placebo , and escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards . Analysis of Clinical Global Impression – Severity and Clinical Global Impression – Improvement confirmed the primary efficacy results . By week 8 , significantly more patients had responded to treatment with escitalopram than with citalopram ( P=0.021 ) or placebo ( P=0.009 ) . Escitalopram was as well tolerated as citalopram and had a similar adverse event profile . Both escitalopram‐ and citalopram‐treated patients had  placebo‐level adverse event withdrawal rates ( 3 % and 4 % , respectively ) . This study demonstrates the consistent antidepressant efficacy and excellent tolerability  of escitalopram 10–20 mg/day in primary care patients with major depressive disorder OBJECTIVE Management of depression in elderly patients presents a significant medical challenge , and there is a need for further clinical trials . The authors examined the efficacy and tolerability of escitalopram and fluoxetine versus placebo in the treatment of elderly patients with major depressive disorder ( MDD ) . METHODS This was an 8-week , r and omized , double-blind comparison of the efficacy and tolerability of escitalopram ( 10 mg/day ) and fluoxetine ( 20 mg/day ) , to placebo in elderly patients with MDD . The prospect ively defined primary efficacy parameter was the change from baseline in mean Montgomery-Asberg Depression Rating Scale ( MADRS ) total score at endpoint , using last observation carried forward . RESULTS The intent-to-treat set comprised 517 patients ; the escitalopram group included 173 patients ; fluoxetine , 164 patients ; and placebo , 180 patients . Mean age was 75 years , with a range of 65 to 93 . Formally , this was a " failed study " ( i.e. , neither active treatment was superior to placebo ) , and the efficacy results should , therefore , be interpreted with caution . On the basis of the primary efficacy parameter , fluoxetine showed significantly lower efficacy than both escitalopram and placebo , which were not significantly different from each other . Rates of withdrawal because of adverse events/lack of efficacy were : placebo ( 2.8%/4.4 % , respectively ) , escitalopram ( 9.8%/1.7 % , respectively ) , and fluoxetine ( 12.2%/1.8 % , respectively ) . No single adverse event occurred at an incidence > or = 10 % in escitalopram-treated patients . CONCLUSIONS Both escitalopram and fluoxetine were well tolerated by elderly patients with MDD . Neither demonstrated superior efficacy on primary endpoint versus placebo 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 OBJECTIVES To compare the sensitivity of the 6-item  Hamilton Rating Scale for Depression  ( HRSD6 ) with the more widely used 17-item  Hamilton Rating Scale for Depression  ( HRSD17 ) in patients suffering from major depressive disorder , with or without melancholia and /or dysthymic disorder . A secondary objective was to compare the sensitivity of the HRSD6 to the Montgomery-Asberg Depression Rating Scale ( MADRS ) . DESIGN Retrospective analysis of 4 clinical trials that tested antidepressant therapies . SETTING Outpatient treatment in a major psychiatric hospital . PARTICIPANTS One hundred and forty-three male and female out patients meeting the criteria of the DSM-III-R or DSM-IV for major depressive disorder . OUTCOME MEASURES HRSD17 , HRSD6 and MADRS . RESULTS The HRSD6 correlated strongly with the HRSD17 , both at baseline and termination of treatment , and for the subgroups of double depression and melancholia . The HRSD6 was also correlated significantly with the MADRS at both measurement times , and for the subgroups . Paired t-tests with the HRSD6 , HRSD17 and MADRS demonstrated equal sensitivity to change over the course of treatment , both in the full sample and in the dysthymic and melancholic subgroups . CONCLUSIONS The HRSD6 appears to be as sensitive to change over treatment as the HRSD17 and the MADRS . A shorter , less time-consuming measure of depression may have utility in clinical practice and research Paroxetine is a selective serotonin reuptake inhibitor with significant antidepressant properties . This was a 6-week placebo- and imipramine-controlled study of 120 out patients with major depression .  Paroxetine was statistically significantly superior to placebo on almost all outcome measures . This was apparent as early as 1 week . Paroxetine was also significantly superior to imipramine on the Hamilton Rating Scale for Depression total score .  Paroxetine was generally better tolerated than imipramine . These results strongly support paroxetine 's effectiveness in the treatment of major depression and suggest that paroxetine will be a valuable addition to the options in treating depressive illness A total of 149 patients in 7 centers in Denmark , Norway and Sweden entered a 6‐week double‐blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients ( 65 years of age or older ) who might also suffer from somatic disorders and /or senile dementia . Results of ratings on the Hamilton Rating Scale for Depression , the Montgomery‐Åsberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram‐treated patients improved more than the placebo‐treated patients . Results of ratings on the Gottfries‐Bråne‐Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram‐treated subgroup of patients with dementia than in the placebo‐treated subgroup Paroxetine , a phenylpiperidine derivative , is an antidepressant that selectively inhibits serotonin reuptake . In this study 111 out patients with major depression diagnosed by DSM-III criteria were treated with either paroxetine or placebo in a 6-week , r and omized , double-blind study . Paroxetine was significantly superior to placebo on six of the seven major efficacy variables . Significant differences in favor of paroxetine were apparent by Week 2 . Paroxetine was also well tolerated . These results support the efficacy and safety of paroxetine as a treatment for patients with major depression Aprepitant is a neurokinin 1 receptor antagonist approved for prevention of chemotherapy‐induced and  post‐operative nausea and vomiting . Early studies demonstrated promising antidepressant activity as monotherapy , although this was unsupported by subsequent phase 3 trials . This phase 2 study evaluated whether aprepitant  potentiated the antidepressant effects of paroxetine
target: Our systematic review in BMC Psychiatry concluded that selective serotonin reuptake inhibitors ( SSRIs ) compared with placebo significantly increase the risk of serious adverse events ( SAEs ) in patients with major depression and the potential beneficial effects of SSRIs seem to be outweighed by the harms .
  In their post-hoc analysis of our data , they reported that SSRIs only increase the risk of SAEs in elderly and seems safe for non-elderly patients .
background: nan