title: Onset and Early Behavioral Effects of Pharmacologically Different Antidepressants and Placebo in Depression Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline A study comparing paroxetine placebo and imipramine in depressed patients. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care Reboxetine, a New Noradrenaline Selective Antidepressant, Is at Least as Effective as Fluoxetine in the Treatment of Depression A double‐blind trial of fluoxetine, 20 mg, and placebo in out‐patients with DSM‐III-R major depression and melancholia Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder. Paroxetine versus placebo: a double-blind comparison in depressed patients. The safety and efficacy of paroxetine compared with placebo in a double-blind trial of depressed outpatients. Fluoxetine, a Selective Serotonin Uptake Inhibitor, for the Treatment of Outpatients with Major Depression Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. The timing, specificity and clinical prediction of tricyclic drug effects in depression. Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients. Sertraline safety and efficacy in major depression: A double-blind fixed-dose comparison with placebo The oral dose-effect relationship for fluvoxamine: a fixed-dose comparison against placebo in depressed outpatients. Use of pattern analysis to identify true drug response. A replication. Identification of true drug response to antidepressants. Use of pattern analysis. A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor. Escitalopram (10–20 mg/day) is effective and well tolerated in a placebo‐controlled study in depression in primary care A placebo-controlled trial of paroxetine in the treatment of major depression. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. A double-blind, placebo-controlled study of paroxetine in depressed outpatients. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression.
abstract: 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 OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy 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 Citalopram is a racemic selective serotonin reuptake inhibitor ( SSRI ) indicated for the treatment of depression . Citalopram is a racemate and its serotonin reuptake inhibitory activity resides primarily in the single S-isomer , escitalopram , which is now being evaluated for its potential usefulness in the treatment of depression and other psychiatric disorders . RESULTS from placebo-controlled studies that also included citalopram as an active control have shown that escitalopram is effective in treating depression and associated symptoms of anxiety . However , none of these studies was powered sufficiently to detect differences between active treatment groups . The goal of the present analysis is to evaluate the efficacy of escitalopram compared with citalopram in the treatment of major depressive disorder . METHOD Data were pooled from three similarly design ed , r and omized , double-blind , placebo-controlled trials of escitalopram ( 10 - 20 mg/day ) and citalopram ( 20 - 40 mg/day ) . Patients were male or female , greater than or equal to 18 years of age , who met criteria for a major depressive episode with a Montgomery Asberg Depression Rating Scale ( MADRS ) score greater than or equal to 22 at baseline . Efficacy measures included change from baseline in MADRS score and the Clinical Global Impression of Improvement ( CGI-I ) scale . Improvement in associated symptoms of anxiety was measured using the change from baseline in the MADRS inner tension item . RESULTS Both escitalopram and citalopram significantly improved depression and anxiety symptoms compared with placebo , and there were significantly more MADRS responders ( defined as > /=50 % improvement in MADRS scores at end point ) in the escitalopram and citalopram treatment groups . Escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment , whereas citalopram treatment statistically separated from placebo at the end of week 4 ( CGI-I and MADRS inner tension ) or week 6 ( MADRS ) . Escitalopram treatment also was statistically significantly superior to citalopram treatment at a number of time points . CONCLUSION These data support the effectiveness of escitalopram and citalopram in the treatment of major depressive disorder , and suggest escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day  ( n = 191 ) or placebo  ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated The clinical profile of reboxetine , a selective noradrenaline reuptake inhibitor , was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind , multicenter , parallel-group clinical trial of patients with major depression . Among the 381 patients treated with reboxetine 8 to 10 mg/day , fluoxetine 20 to 40 mg/day , or placebo for up to 8 weeks , a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression ( 21-item HAM-D ) total score ( the primary efficacy variable ) was seen for both active treatment groups compared with placebo ( p < 0.024 ) . A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response ( ≥50 % reduction in HAM-D ) or remission ( HAM-D ≤10 points ) than those who received placebo ( p < 0.01 for both analyses ) . Similar findings were recorded in a sub population of severely ill patients , with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo ( p < 0.024 ) . Additional efficacy assessment s ( Montgomery-Åsberg Depression Rating Scale , Clinical Global Impression ) reflected the primary efficacy analysis , with both active treatments offering comparable efficacy that was superior to that of placebo . Reboxetine and fluoxetine are more effective  than placebo in the treatment of major depression . Futhermore , both antidepressants are well tolerated but possess different adverse event profiles As part of a study in which reduced rapid eye movement latency was used to predict treatment response , fluoxetine and placebo were compared in 89 out patients with major depression with ( n = 52 ) and without ( n = 37 ) DSM-III-R melancholia , to determine whether the presence or absence of melancholia predicted antidepressant and /or placebo response . Following a 2-week , single blind placebo lead-in , men and women were assigned by r and om allocation to double-blind fluoxetine , 20 mg/day , or placebo for 8 weeks . Fluoxetine was statistically significantly superior to placebo in patients with melancholia  ( endpoint change in the Montgomery-åsberg Depression Rating Scale [ MADRS ] score , response rates and remission rates ) . A weekly analysis demonstrated statistical superiority of fluoxetine compared with placebo at week 3 and continuing for the remainder of the study . Fluoxetine was statistically significantly more likely to reduce suicidal ideation compared with placebo , using the MADRS item 10 ( suicidal ideation question ) CONTEXT Paroxetine controlled release ( CR ) is approved for the treatment of major depressive disorder ( MDD ) in the dosage range of 25 to 62.5 mg daily . However , lower daily doses ( 12.5 mg and 25 mg ) of this formulation have not been investigated in the treatment of MDD . If the 12.5-mg and 25-mg doses are found to be efficacious , these lower doses may well convey a superior tolerability profile for paroxetine CR in the treatment of MDD . OBJECTIVE To evaluate the antidepressant efficacy and tolerability profile of daily doses of paroxetine CR 12.5 mg and 25 mg versus placebo in the treatment of MDD . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 40 clinical investigation centers in the United States . PARTICIPANTS 447 adult ( > or = 18 years of age ) out patients who met DSM-IV criteria for MDD and with a baseline 17-item Hamilton Rating Scale for Depression ( HAM-D ) score of at least 20 comprised the intent-to-treat study population ( mean age = 38.8 years ; 58.4 % female ; 75.6 % white ) . INTERVENTION Eligible patients completing a 1-week single-blind placebo run-in period were r and omly assigned to receive once-a-day study medication ( paroxetine CR 12.5 mg [ N = 156 ] , paroxetine CR 25 mg [ N = 154 ] , or placebo [ N = 149 ] ) in an 8-week , double-blind , parallel cell comparison . MAIN OUTCOME MEASURES The primary efficacy measure was the change from baseline to study endpoint ( week 8) as measured by the HAM-D. Secondary efficacy measures included change from baseline to study endpoint as assessed by both the depressed mood item on the HAM-D and the Clinical Global Impressions ( CGI ) Severity of Illness scale ( CGI-S ) . The proportion of patients considered at study endpoint to be in response ( CGI-Improvement score of 1 or 2 ) or in remission ( HAM-D < or = 7 ) in the 3 treatment groups was also compared . Quality of life was assessed by the change from baseline in total score of the short form of the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) . Safety observations were made by assessing the proportion of patients who had adverse experiences , including laboratory and electrocardiographic abnormalities , during the treatment period . RESULTS The primary efficacy analysis revealed that both the 12.5-mg and the 25-mg paroxetine CR treatment groups were associated with significant therapeutic effects ( change in HAM-D score ) from baseline to study endpoint ( LOCF : p = .038 , 95 % CI = -3.38 to -0.09 and p = .005 , 95 % CI = -4.06 to -0.74 , respectively ) . Results from the Wilcoxon rank sum test of the depressed mood item of the HAM-D ( p = .011 , 95 % CI = -0.57 to -0.07 ) demonstrated significant efficacy in the 25-mg treatment group but not in the 12.5-mg group . However , LOCF analysis of the CGI-S revealed significant therapeutic effects for both the 12.5-mg ( p = .018 , 95 % CI = -0.61 to -0.06 ) and 25-mg ( p < .001 , 95 % CI = -0.78 to -0.22 ) treatment groups . Significantly more patients in the 25-mg paroxetine CR-treated group than in the placebo-treated group met criteria for response ( CGI-Improvement score of 1 or 2 , p = .035 , OR = 1.68 , 95 % CI = 1.04 to 2.73 ) as well as for remission ( HAM-D score < /= 7 , p = .013 , OR = 1.96 , 95 % CI = 1.15 to 3.33 ) . Neither HAM-D remission analysis nor CGI responder analysis showed statistical separation from placebo for paroxetine CR 12.5-mg treatment . Quality of life improvements were statistically significant for the 25-mg treatment ( p = .041 , 95 % CI = 0.17 to 8.03 ) on the Q-LES-Q total score . Post hoc LOCF analyses of HAM-D sleep disturbance , psychic anxiety , and anxiety/somatization factors revealed significant improvements from baseline in the paroxetine CR 25-mg and 12.5-mg treatment groups . The types of adverse events reported in the 12.5-mg and 25-mg groups were similar to those reported with paroxetine CR at the customary 25-mg to 62.5-mg range ; however , the lower doses of paroxetine CR were associated with a relatively reduced incident rate of these adverse events and an overall improved tolerability compared with the incident rate and tolerability profile associated with the customary dose range of paroxetine CR ( 25 to 62.5 mg ) . CONCLUSION Paroxetine CR , at 12.5 mg/day and 25 mg/day , demonstrated significant antidepressant effects BACKGROUND Paroxetine is a potent and selective serotonin reuptake inhibitor ( SSRI ) . The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed out patients . METHOD A double-blind , parallel-group study was undertaken in four st and -alone centers . Patients aged 18 - 65 years , meeting DSM-III criteria for major depression , and having a Hamilton Rating Scale for Depression ( HAM-D ) score > or = 18 on the first 17 items of the HAM-D-21 were r and omized to paroxetine or placebo for 6 weeks of treatment . Efficacy outcome variables included the HAM-D , the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impressions Scale ( CGI ) , and the Covi Anxiety Scale . Tolerability was assessed by asking a non-leading question . Routine laboratory safety and vital sign data from all four centers were pooled . The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed . Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables . RESULTS Significant differences ( p < or = .05 ) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4 . Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor . Similar results were obtained when an adequate treatment group ( therapy for > or = 28 days ) was considered . A full clinical response ( CGI-severity of illness score 1 or 2 ) was seen in over 40 % of subjects . Adverse events were more common for paroxetine compared with placebo ( p < or = .01 ) . Somnolence was twice more common than nervousness . Dropout due to adverse events was similar between therapies . Paroxetine had no clinical ly significant effect on laboratory safety data or vital signs . CONCLUSION Paroxetine was an effective , well tolerated , and safe antidepressant . Side effects were typical of the SSRI class of drugs . Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects Considerable research shows that serotonin dysfunction is implicated in major depression .  Paroxetine is an investigational antidepressant that appears to act by selectively blocking neuronal serotonin uptake . Seventy-two out patients with moderate-to-severe major depression entered this 6-week , double-blind comparison of paroxetine and placebo . The results showed clear and significant superiority of paroxetine on all of the major outcome variables . These included physician-rated measures such as the Hamilton Rating Scale for Depression and its four factor scores , the Clinical Global Impressions scale , the Montgomery and Asberg Depression Rating Scale , and the Raskin Depression Scale . Results on these agreed well with patient-rated measures like the Hopkins Symptom Checklist and Patient Global Evaluation Scale .  Paroxetine was also very well tolerated . Nausea and constipation occurred significantly more often with paroxetine , but only 9 % of paroxetine patients dropped out of the study due either in whole or in part to an adverse effect . This compares to 8 % of the placebo patients who were discontinued for the same reason . This study suggests that paroxetine is a safe and effective medication for the treatment of major depression In a double-blind , placebo-controlled study the authors found that fluoxetine , a potent and selective inhibitor of serotonin reuptake , was an effective antidepressant in moderately depressed , ambulatory out patients . Typical adverse effects reported by patients treated with fluoxetine  included agitation , nausea , fatigue , and insomnia . Compared to imipramine , fluoxetine was associated with fewer complaints of dry mouth , constipation , and dizziness OBJECTIVE The present study aim ed to 1 ) assess facial expression recognition in subjects with a previous history of major depressive disorder relative to subjects with no history of depression and 2 ) characterize the effects of acute citalopram infusion on recognition performance for both groups . METHOD Unmedicated euthymic women with a history of major depression and matched comparison subjects with no history of depression were given a facial expression  recognition task following intravenous infusion of saline or citalopram ( 10 mg ) in a double-blind , between-group design . RESULTS Following saline infusion , subjects with a previous history of depression showed a selectively greater recognition of fear relative to the subjects with no history of depression . The abnormal fear processing observed in the subjects with a previous history of depression was normalized following citalopram infusion , an effect that was opposite to that seen with the subjects with no history of depression . CONCLUSIONS These results suggest that increased recognition of fear is a trait vulnerability marker for depression and that this is normalized following a single dose of citalopram BACKGROUND We conducted a r and omized , double-blind , placebo-controlled study of the efficacy and safety of once-daily venlafaxine extended release ( XR ) and fluoxetine in out patients with major depression and concomitant anxiety . METHOD Patients who met DSM-IV criteria for major depressive disorder and satisfied eligibility criteria were r and omly assigned to once-daily venlafaxine XR , fluoxetine , or placebo for 12 weeks . Efficacy was assessed with the Hamilton Rating Scale for Depression ( HAM-D ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scale . RESULTS Among 359 out patients , venlafaxine XR and fluoxetine were significantly superior ( p < .05 ) to placebo on the HAM-D total score beginning at week 2 and continuing to the end of the study . Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2 on the HAM-D depressed mood item . At week 12 , the HAM-D response rate was 43 % on placebo , 67 % on venlafaxine XR , and 62 % on fluoxetine ( p < .05 ) . The HAM-D remission rate was significantly higher ( p < .05 ) at weeks 3 , 4 , 6 , 8 , 12 , and final evaluation with venlafaxine XR and at weeks 8 , 12 , and final evaluation with fluoxetine than with placebo . The HAM-A response rate was significantly higher ( p < .05 ) with venlafaxine XR than with fluoxetine at week 12 . The incidence of discontinuation for adverse events was 5 % with placebo , 10 % with venlafaxine XR , and 7 % with fluoxetine . CONCLUSION Once-daily venlafaxine XR is effective and well tolerated for the treatment of major depression and concomitant anxiety and provides evidence for superiority over fluoxetine This research was aim ed at study ing the rate of action of tricyclic drugs in depressive disorders , specifying the behavioural effects associated with recovery , and predicting clinical response . The research design involved comparison of a recovered group with a group treated for the equivalent four weeks , who showed minimal to no response . The findings indicated significant differences in baseline characteristics between responders and non-responders . Further , the drugs were found to act early in the responders , within the first week of treatment . Specific changes at one week which distinguished responder and non-responder groups occurred in the disturbed affects , and in cognitive functioning . Improvements also occurred in somatic symptoms , but these latter changes were general and not associated with later recovery . At 2 1/2 weeks , all facets of the depressed condition showed positive change in the responders . Implication s of the results for assessing rate of tricyclic drug actions , their effects on the interaction of affect and neurochemistry , and the practical application of the results for the clinical situation , are discussed 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 In a 6-week , r and omized , double-blind , multicenter trial , sertraline 50 mg , 100 mg , or 200 mg , or placebo , was administered once daily to 369 patients with DSM-III-defined major depression . Efficacy variables included changes from baseline scores for total Hamilton Rating Scale for Depression ( HAMD ) , HAMD Bech Depression Cluster , Clinical Global Impressions ( CGI ) Severity , CGI Improvement , and Profile of Mood States Depression/Dejection Factor . For the evaluable- patients analysis , all sertraline groups showed significantly ( p < 0.05 or better ) greater improvements in all efficacy variables except one when compared with the placebo group . For the all- patients analysis , all efficacy variables in the 50 mg group were statistically significantly ( p < 0.05 ) better than placebo .  Side effects increased with increasing dosage but were usually mild and well tolerated . The results of this study show that sertraline 50 mg once daily is as effective as higher dosages for the treatment of major depression with fewer side effects and therapy discontinuations This 7- to 8-week , multicenter , r and omized , double-blind , placebo-controlled study was performed to determine the dose-effect relationship and minimum effective dose for fluvoxamine maleate in a titrated fixed-dose study of major depressive disorder . Gradual titration over 2 weeks to fixed maintenance doses was employed to minimize dropout due to initial side effects . The study enrolled 600 out patients , male and female , age 18 - 65 , meeting DSM-III-R criteria for major depressive disorder . A 13-item subscore of the st and ard 21-Item Hamilton Depression Scale was used to minimize the possible contribution of known side effects from serotonin reuptake inhibitors to the overall HAM-D score . Secondary efficacy assessment s included the HAM-D retardation factor , HAM-D depressed mood item , CGI-severity of illness item , and SCL depression factor .  Fluvoxamine ( 50 - 150 mg/day ) was therapeutically effective and well tolerated during 6 weeks of therapy . Based on the HAM-D depressed mood item , efficacy was dose dependent . The minimum effective dose was 50 mg/day . Fluvoxamine maleate shows dose-related effectiveness in the acute treatment of major depressive disorder In any antidepressant study , placebo response in patients assigned active drug is a troubling source of variance . There have been few attempts to identify the patients whose conditions improve as a result of true drug effect , in contrast with improvement that is a result of nonspecific effects . In a previous report we demonstrated that true drug effect seemed to be characterized by a two-week delay in onset and persistence . We described a method of pattern analysis to identify such patients . In this report , we describe the use of pattern analysis to replicate our initial findings . Data from a new sample of 150 nonmelancholic patients support the hypothesis that true drug effect is characterized by a two-week delay in onset and persistence of improvement , once achieved . There was little evidence of the onset of antidepressant effect before two weeks . The theoretical and clinical implication s of this work are discussed The purpose of this study was to develop a method for differentiating specific ( " true " ) and nonspecific antidepressant drug response for the individual patient . Patterns of clinical response , based on weekly global ratings of clinical status , were generated for each of 185 patients participating in six-week placebo-controlled drug trials .  We hypothesized and found that substantially more patients receiving active than placebo medication displayed treatment response patterns characterized both by two-week or greater delay in onset of initial improvement and nonfluctuating persistence of improvement once achieved . Identification of a distinctive pattern of clinical response to an active drug has both research and clinical applications . Pattern analysis may contribute to underst and ing the nature of drug mechanisms of action , may clarify some ambiguous treatment study outcomes , and in the individual case , may facilitate clinical management 1 . The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 out patients with major depressive disorder . 2 . Although overall drug effects were relatively weak , there were trends suggesting separation of both active drugs from placebo at week six . Both drugs were well tolerated . 3 . Studies of major depression ought to be design ed to last 8 - 10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks OBJECTIVE The authors used magnetic resonance spectroscopy ( MRS ) to assess the effect of acute administration of the selective serotonin reuptake inhibitor ( SSRI ) citalopram on cortical levels of gamma-aminobutyric acid ( GABA ) . METHOD Ten healthy volunteers received either intravenous citalopram ( 10 mg ) or saline in a r and omized , double-blind , crossover design . The occipital GABA/creatine ratio was measured with a proton MR spectral editing technique . RESULTS In comparison with saline , citalopram produced a mean increase of 35 % in relative brain GABA concentration in the occipital cortex . CONCLUSIONS These findings extend previous work showing that SSRI treatment increases cortical GABA in depressed patients and suggest that this results from an action of SSRIs on GABA neurons rather than as a secondary consequence of mood improvement & 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 Paroxetine is a phenylpiperidine compound that selectively inhibits neuronal serotonin uptake in man . In this study , the efficacy of paroxetine was compared with that of placebo in the treatment of 66 out patients with the diagnosis of moderate-to-severe major depression . The research was a 6-week , prospect i ve , double-blind design after a 1-week placebo baseline phase . Paroxetine was associated with a consistent pattern of greater improvement on the primary efficacy scales , but the differences were not statistically significant . Paroxetine did produce significantly greater improvement than placebo for patients whose illness had lasted more than 1 year , and there was a significant reduction in suicidal ideation . Significantly fewer dropouts were due to lack of efficacy in those patients treated with paroxetine compared with those in the placebo group . Paroxetine was well tolerated . There was no difference between paroxetine and placebo in the rate of adverse effects or in the number of patients who dropped out because of adverse effects A double-blind , placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline , a specific serotonin uptake inhibitor . Patients with DSM-III-defined major depression r and omly received either sertraline  ( N = 149 ) , amitriptyline ( N = 149 ) , or placebo ( N = 150 ) once daily for the 8-week study period . The mean final daily medication dose for the all- patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups , respectively . As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale , both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline ( p less than or equal to .001 ) than the placebo group . The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group . The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo Paroxetine is an investigational antidepressant that acts through selective inhibition of serotonin reuptake at the synapse . In this study , 81 out patients with major depression according to 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 all major efficacy variables , including depression as well as anxiety , cognitive disturbance , insomnia , psychomotor retardation , and sleep disturbance . Significant differences in favor of paroxetine were apparent by Week 2 . Paroxetine was also well tolerated . The results support the efficacy and safety of paroxetine as a treatment for patients with major depression Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant to be marketed in the U.S. In this double-blind trial fluoxetine was compared with imipramine and placebo among 198 out patients with DSM-III major depression , of whom 145 completed at least 2 weeks of active treatment and were evaluated for efficacy . Significantly fewer patients in each active drug group terminated early due to lack of efficacy compared to placebo . Both imipramine and fluoxetine were significantly superior to placebo on most measures . There were no consistently significant differences between the two active drugs although a trend favored imipramine on a number of measures . Fluoxetine was generally well tolerated . Significantly more imipramine than placebo patients terminated early due to side-effects while the fluoxetine-placebo difference was not significant . The results support previous studies which suggest fluoxetine 's superior side-effect profile and the approximate antidepressant equivalence of fluoxetine and TCAs
target: Treatment with SSRIs rather than placebo was associated with clinical improvement by the end of the first week of use .
  CONCLUSIONS Treatment with SSRIs is associated with symptomatic improvement in depression by the end of the first week of use , and the improvement continues at a decreasing rate for at least 6 weeks
background: CONTEXT Selective serotonin reuptake inhibitors ( SSRIs ) are often described as having a delayed onset of effect in the treatment of depression .
  However , some trials have reported clinical improvement as early as the first week of treatment .
  OBJECTIVE To test the alternative hypotheses of delayed vs early onset of antidepressant action with SSRIs in patients with unipolar depression .