A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients

This double-blind, placebo-controlled study compared venlafaxine (immediate release), the first modern serotonin-norepinephrine reuptake inhibitor, with the selective serotonin reuptake inhibitor fluoxetine. Outpatients were randomly assigned to 6 weeks of treatment with venlafaxine (75-225mg/day; n=102), fluoxetine (20-60mg/day; n=104), or placebo (n=102). Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HAM-D(21)), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression-Severity of Illness (CGI-S) scale, response and remission rates, and several other measures. Intent-to-treat analyses utilized both the last observation carried forward and ETRANK methods to account for missing data. At week 6 or study endpoint, venlafaxine (mean dose: 142mg/day) was superior to placebo on most outcomes measures, whereas the differences between fluoxetine (mean dose: 41mg/day) and placebo were less consistent. Final remission (defined as HAM-D < or =7) rates were 32%, 28%, and 22% for venlafaxine, fluoxetine, and placebo, respectively. Few differences between the active treatments attained statistical significance. Both active therapies were generally well tolerated; however, attrition due to adverse events, incidence of selected side effects, and increases in pulse and blood pressure favored fluoxetine over venlafaxine. This study provides further evidence that venlafaxine is effective after 6 weeks of treatment compared with placebo. The efficacy profile of fluoxetine was somewhat less consistent. It is strongly recommended that future studies of comparative antidepressant efficacy be adequately powered to detect modest between-drug differences in efficacy.     

A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression

The authors employed a double-blind, placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 outpatients with moderate major depression. Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale. Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients.     

Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram

BACKGROUND: The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75-150 mg/day with that of citalopram 10-20 mg/day in elderly patients with major depression according to DSM-IV criteria. METHODS: A randomised, double-blind, parallel group 6-month study. Efficacy was assessed by MADRS, CGI Global Improvement, CGI Severity of Illness and GDS-20 scores and safety by physical examinations, vital signs, adverse events and UKU side effect rating. Plasma levels of venlafaxine, its major metabolite O-desmethylvenlafaxine and citalopram were followed. RESULTS: One hundred and fifty-one male and female patients (64-89 years) were enrolled and 118 patients completed the study. Comparable improvements in MADRS, CGI Severity of Illness, CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment. The MADRS remission rate was 19% for venlafaxine and 23% for citalopram. Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment. There were no clinically significant changes in blood pressure or body weight. CONCLUSION: The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects. Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram.     

Transdermal selegiline in major depression: a double-blind,placebo-controlled,parallel-group study in outpatients

OBJECTIVE: The authors investigated the efficacy and safety of transdermal selegiline in adult outpatients with major depressive disorder. METHOD: Following a 1-week placebo lead-in, 177 adult outpatients with major depressive disorder were randomly assigned to receive transdermal selegiline (20 mg applied once daily by means of a 20-cm(2) patch) (N=89) or placebo (N=88) for 6 weeks. The patients followed a tyramine-restricted diet during the medication trial and for 2 weeks after completion of treatment. Response to medication or placebo was measured by using the 17-item and 28-item versions of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression (CGI) severity and improvement measures. RESULTS: Greater improvement was observed after 6 weeks in patients treated with transdermal selegiline than in those given placebo according to all measures. A statistically significant difference between drug and placebo was seen in Hamilton depression scale and Montgomery-Asberg Depression Rating Scale scores as early as week 1 of treatment. There were no differences in the adverse event profile of the patients given selegiline and those given placebo with the exception of application-site reactions, which were more common with the selegiline transdermal system. No orthostatic hypotensive or hypertensive reactions were observed. CONCLUSIONS: Transdermal selegiline (20 mg applied once daily by means of a 20-cm(2) patch) administered for 6 weeks was an effective and well-tolerated treatment for adult outpatients with major depression. The typical side effects commonly seen with traditional monoamine oxidase inhibitor antidepressants were not observed.     

An 8-week multicenter,parallel-group,double-blind,placebo-controlled study of sertraline in elderly outpatients with major depression

OBJECTIVE: There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients. This placebo-controlled study of sertraline was designed to confirm the results of non-placebo-controlled trials. METHOD: The subjects were outpatients 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 randomly 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 evidenced 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.     

A randomized, double-blind study of fluoxetine and maprotiline in the treatment of major depression.

In a six-week double-blind randomized trial, preceded by a one-week single-blind placebo treatment, the efficacy and the side-effects of fluoxetine (40-80 mg/d) (n = 30) and maprotiline (50-150 mg/d) (n = 35) were compared in hospitalized patients with DSM-III Major Depression without psychotic features. Efficacy was measured by means of the Hamilton Depression Rating Scale, the Raskin Depression Scale, the Covi Anxiety Scale, and a Clinical Global Impression. Side-effects were evaluated by an Adverse Events Scale. A statistically significant improvement was achieved in both treatment groups but success rates were modest. No differences in efficacy were found between the two groups. In addition, no statistically significant differences were found between the two groups either in frequency or in severity of adverse events. In fact, the only statistically significant difference found was in weight change: weight loss in the fluoxetine group and weight gain in the maprotiline group.     

A fixed-dose clinical trial of fluoxetine in outpatients with major depression

Fixed daily doses of 20 mg, 40 mg, or 60 mg of fluoxetine, a highly specific serotonin reuptake inhibitor, were given to 84 depressed outpatients in a double-blind, placebo-controlled, randomized 6-week trial. The 20-mg dose produced improvement of depression in the moderate-severe depression group as expressed in significant reductions of scores on the Hamilton Rating Scale for Depression (p greater than or equal to .007) and the Patient Global Impressions scale (p greater than or equal to .011), and the 20-mg dose caused fewer side effects than did the higher doses. A mildly depressed group of patients showed no improvement at any dose level of fluoxetine.     

A placebo-controlled double-blind randomized study of venlafaxine in the treatment of depression in dementia

BACKGROUND/AIMS: To evaluate the efficacy and safety of venlafaxine in the treatment of major depression in dementia. METHODS: Thirty-one outpatients who had dementia and major depression participated in this randomized, double-blind, placebo-controlled, 6-week, flexible dose clinical trial. The screening measures were Cornell Scale for depression in dementia, DSM-IV for depression and dementia and Mini-Mental State Examination. The outcome measures were response rate, Montgomery-Asberg Depression Rating scale and Clinical Global Impressions. RESULTS: The percentage of patients defined as Montgomery-Asberg Depression Rating scale responders was approximately the same in the placebo and in the venlafaxine groups. Clinical Global Impressions showed no significant difference between the groups. The reasons for dropouts show borderline significance between the two groups. There was no statistically significant difference in the incidence of adverse events between the venlafaxine and placebo-treated groups. CONCLUSIONS: Our data do not support the hypothesis that venlafaxine improves mood in elderly demented patients.     

万拉法新和氟西汀治疗抑郁症的对照研究

目的：对比分析万拉法新与氟西汀治疗抑郁症的疗效和副作用。方法：采用随机分组的对照实验方法，将符合中国精神疾病分类方案和诊断标准第2版修订本抑郁症标准59例抑郁症患者随机分为万拉法新组（32例）和氟西汀组（27例），治疗6周，用汉密尔顿抑郁量表和副反应量表评定两组药的疗效和不良反应。结果：万拉法新和氟西汀疗效及不良反应相近。万拉法新起效更迅速，增加剂量可提高疗效，量效关系较为明显，部分病例氟西汀静坐不能反应可持续存在至疗程结束，结论：万拉法新治疗抑郁症起效迅速。副作用轻微。     

A placebo-controlled, double-blind crossover study of fluoxetine in trichotillomania

OBJECTIVE: It has been proposed by some investigators that trichotillomania, a disorder of chronic hair pulling, is a variant of obsessive-compulsive disorder, and some studies have suggested that the antiobessional agents clomipramine and fluoxetine are useful in treating this disorder. The authors investigated the efficacy of fluoxetine in the treatment of trichotillomania. METHOD: Twenty-one adult chronic hair pullers were recruited into an 18-week placebo-controlled, double-blind crossover study of fluoxetine, in doses up to 80 mg/day. The fluoxetine and placebo treatment phases consisted of 6-week trials of each agent separated by a 5-week washout period. Fifteen subjects (14 female and one male) completed the study; an additional female subject dropped out at 16 weeks after developing a drug reaction. RESULTS: No significant Drug by Period interactions were found in weekly subject ratings of hair pulling, weekly subject ratings of the urge to pull hair, weekly assessments of the number of hair-pulling episodes, or the estimated amount of hair pulled per week. CONCLUSIONS: The short-term efficacy of fluoxetine in the treatment of trichotillomania was not demonstrated in this study.     

A double-blind, placebo-controlled study of memantine in the treatment of major depression

OBJECTIVE: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans. METHOD: In a double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned to receive memantine (5-20 mg/day) (N=16) or placebo (N=16) for 8 weeks. Primary efficacy was assessed by performance on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The linear mixed models for total MADRS scores showed no treatment effect. CONCLUSIONS: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder.     

A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression

Based on preliminary evidence of its usefulness in treatment-resistant depression (TRD), an olanzapine/fluoxetine combination (OFC) was examined in comparison with olanzapine, fluoxetine, and venlafaxine in a TRD population. In this 12-week double-blind study, 483 subjects with unipolar, nonpsychotic TRD, with historic failure on a selective serotonin reuptake inhibitor (SSRI) and prospective failure on open-label venlafaxine, were randomized to an OFC or to an olanzapine, fluoxetine, or venlafaxine monotherapy group. Venlafaxine was continued randomly in the double-blind acute phase to explore the benefits of continuation versus switching therapy. The Montgomery-Asberg Depression Rating Scale (MADRS) total change score at end point was the primary outcome measure. The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment (MADRS mean change =-7.2, baseline =29.6), in comparison to olanzapine (-4.8, P=.03), fluoxetine (-4.7, P=.03), or venlafaxine (-3.7, P=.002) groups and maintained its statistical separation from all three monotherapy groups through week 6. At end point, the OFC group was significantly different only from the olanzapine group (-14.1 vs. -7.7, P<.001). Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode (n=334) revealed statistical separation from both olanzapine and fluoxetine (but not venlafaxine) at end point: OFC (-14.6) versus olanzapine (-9.4, P<.001) versus fluoxetine (-10.7, P=.006) versus venlafaxine (-14.7, P=.98). The OFC had a safety profile comparable to its component monotherapies (i.e., olanzapine and fluoxetine), showed a rapid onset of antidepressant effect, and was effective in this TRD sample. At the study end point, OFC, fluoxetine, venlafaxine, and low-dose OFC all appeared to be similarly effective.     

A comparative trial of fluoxetine versus trazodone in outpatients with major depression

The effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients. The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment. However, that difference was no longer apparent during the remainder of the study. The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone.     

A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease

OBJECTIVE: To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD). METHODS: This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures. RESULTS: Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild. CONCLUSION: Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD.     

A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group

BACKGROUND: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. METHODS: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. RESULTS: Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. CONCLUSION: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.     

文拉法辛与氟西汀治疗抑郁症伴躯体症状对照研究

目的：比较文拉法辛与氟西汀治疗抑郁症伴躯体症状的临床疗效。方法：将77例患者随机分为两组,分别给予文拉法辛与氟西汀治疗6周,用汉密尔顿抑郁量表（HAMD）和治疗中出现的症状量表（TESS）作为评定指标分别于治疗前后评定疗效和不良反应。结果：文拉法辛组总有效率和临床治愈率分别为89.74%和66.67%,明显高于氟西汀组（分别为71.05%和39.47%）;两组HAMD评分治疗后均显著下降（P〈0.01）,文拉法辛组总分和焦虑/躯体化因子分,明显低于氟西汀组（P〈0.05）。结论：在治疗躯体症状方面,文拉法辛优于氟西汀。     

文拉法辛与氟西汀治疗抑郁症的临床对照研究

目的评价文拉法辛治疗抑郁症的临床疗效和安全性。方法将120例抑郁症患者随机分为试验组和对照组各60例,试验组用文拉法辛治疗,起始剂量50mg/d,7~10d加至75~225mg/d;对照组用氟西汀治疗,起始剂量为20mg/d,7~10d内加至40mg/d,两组mg/d疗程均为6周。用汉密顿抑郁量表(HAMD)、临床疗效总评量表病情严重程度(CGI-SI)、和副反应量表(TESS)评价疗效和不良反应。结果实验组完成57例,有效率为84.2%,对照组完成58例,有效率为82.8%,两组mg/d有效率差异无显著性(P<0.05),显效时间实验组为(6.7±3.3)d,对照组为(10.2±4.7)d,试验组显效较早(P<0.05)。TESS评分两组mg/d差异无显著性(P>0.05)。治疗第6周末两组HAMD和CGI-SI评分差异无显著性,治疗6周末两组mg/dTESS评分差异无显著性(P>0.05)。结论文拉法辛起效快,副反应小,是一种安全有效的抗抑郁新药。     

The use of pindolol with fluoxetine in the treatment of major depression: final results from a double-blind, placebo-controlled trial.

BACKGROUND: Preliminary reports have suggested that concomitant institution of pindolol and serotonin reuptake inhibitors robustly hastens clinical response; however, contradictory evidence from a randomized double-blind, controlled trial was recently reported by this group in a population of depressed patients who were prescribed fluoxetine and pindolol. Herein, we report final results from an extended sample size. METHODS: Drug-free outpatients with a major depressive episode were randomized in a double-blind manner to one of two treatment conditions: fluoxetine (20 mg daily) with pindolol (7.5 to 10 mg daily) or fluoxetine (20 mg daily) with placebo. After 6 weeks, patients were followed for 3 more weeks in a single-blind manner, on fluoxetine and placebo pindolol. RESULTS: Eighty-six patients completed at least 1 or more weeks on protocol, with 45 and 41 patients randomized to the pindolol and placebo groups respectively. After 2 weeks on protocol, partial remission (i.e., at least 50% decrease in depression rating scores from baseline) rates for pindolol (16%) and placebo (19%) groups were comparable. By the study's end, a partial remission was achieved, at least transiently, for 67% of the pindolol group and 80% of the placebo group. Pindolol treatment was associated with statistically significant reduction in blood pressure and pulse as compared to the control group. The two groups did not have overall differences in rates of attrition, time to response, and side effects. CONCLUSIONS: In accord with our previously published findings, these extended results do not support the efficacy of pindolol in hastening clinical response to fluoxetine in a patient population with predominantly chronic and recurrent depression.