title: Sertraline Treatment of Co-occurring Alcohol Dependence and Major Depression Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo-controlled trial Double-blind comparison of citalopram and placebo in depressed outpatients with melancholia. Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. 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 in the treatment of depressed elderly patients. A 6-week, double-blind trial of paroxetine, imipramine, and placebo in depressed outpatients. A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia 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: 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 Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder ( MDD ) treatment in adults . This was a 10-week , multicenter , double-blind , placebo-controlled and active-controlled , fixed-dose trial ( NCT01473381 ) . Adult patients with MDD ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , text revision criteria ) were r and omized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day , citalopram 40 mg/day , or placebo . Primary efficacy : Montgomery – Åsberg Depression Rating Scale ( MADRS ) ; secondary efficacy : Clinical Global Impressions-Severity and sustained response ( MADRS total score⩽12 for at least the last two consecutive double-blind visits ) . The intent-to-treat population comprised 1133 patients , ( placebo=281 ; vilazodone 20 mg/day=288 ; vilazodone 40 mg/day=284 ; citalopram=280  ) . MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day , vilazodone 40 mg/day , and citalopram versus  placebo . Sustained response rates were numerically higher , but not significantly different , in all active treatment groups versus placebo . The most common adverse events ( ≥5 % of vilazodone patients , twice the rate of placebo ) were diarrhea , nausea , vomiting  ( vilazodone 40 mg/day only ) , and insomnia . Improved sexual function ( Changes in Sexual Functioning Question naire scores ) was seen in all groups ; between-group differences were not significant . Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD This multicenter study compared the efficacy and safety of citalopram and placebo in a population of moderately to severely depressed patients with melancholia . This r and omized , double-blind , parallel-group study compared citalopram ( flexible dose ; 20 - 80 mg/day ) with placebo in 180 psychiatric out patients with a DSM-III diagnosis of major depression or bipolar disorder , depressed , who also met DSM-III criteria for melancholia . Following a 1-week placebo washout period , patients meeting study entry criteria were r and omized to 4 weeks of double-blind treatment with either citalopram or placebo .  Efficacy measures included the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) Scale , and the Zung Self-Rating Depression Scale . Patients treated with citalopram showed significantly greater improvement at endpoint than placebo patients on the HAM-D , CGI , and Zung scales . On the HAM-D , citalopram patients exhibited significantly greater improvement than placebo patients after 1 week of double-blind treatment and at all subsequent study visits . Endpoint analyses of the HAM-D subscales demonstrated that citalopram produced significant improvement of the psychomotor retardation , cognitive disturbance , sleep disturbance , and melancholia symptom clusters . Nausea , dry mouth , somnolence , dizziness , and increased sweating were reported at higher rates by citalopram-treated patients than by placebo-treated patients , but there were no significant citalopram-placebo differences in the incidence of activation ( e.g. , anxiety , nervousness , insomnia ) or sexual dysfunction . Analysis of electrocardiograms , vital signs , and laboratory tests did not reveal any clinical ly significant effects of citalopram treatment . The results of this study indicate that citalopram is safe and effective in the treatment of depressed patients with melancholia , and is associated with a favorable side effect profile and a potentially rapid onset of action BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness 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 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 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 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 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 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: After having corrected for these apparent mistakes , we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age ; while this suggests SSRIs to be safe drugs in the non-elderly , they do confirm what is already known , that is , that they may enhance the risk for SAEs in the old .
background: According to a systematic review on the use of selective serotonin reuptake inhibitors ( SSRIs ) in adult depression that was recently published in BMC Psychiatry , the results of which have been widely disseminated in lay media , these drugs increase the risk for serious adverse events ( SAEs ) while exerting poor antidepressant efficacy .