A double-blind comparison of fluoxetine, imipramine and placebo in outpatients 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 outpatients 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.     

A double-blind study of the efficacy and safety of sertraline and clomipramine in outpatients with severe major depression

This study compared the efficacy and safety of the selective serotonin reuptake inhibitor sertraline with that of the tricyclic antidepressant clomipramine in patients with severe depression, as defined by a baseline 17-item Hamilton Depression Rating Scale (HAM-D) of at least 25. The study included 166 outpatients, randomized to double-blind treatment with sertraline (50-200 mg) or clomipramine (50-150 mg) for 8 weeks. The efficacy of both treatments was similar, 74% of patients in the sertraline group and 71% of clomipramine patients being classified as responders at the end-point, as defined by a Clinical Global Impression-Improvement (CGI-I) score of 1 or 2. Mean HAM-D scores fell from 29.8 at baseline to 12.3 at endpoint in the sertraline group, and from 29.6-12.7 in the clomipramine group. There were more withdrawals due to adverse events in the clomipramine group than in the sertraline group (17% versus 12%). Dry mouth, tremor, dizziness and constipation were all substantially more common in the clomipramine group, whereas diarrhoea/loose stools was more common in the sertraline group. Overall, sertraline was as effective as clomipramine in this group of severely depressed outpatients, and showed better tolerability.     

Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia

The purpose of this study was to compare the efficacy and tolerability of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. This was an 8-week, multicentre, randomized, double-blind, parallel-group comparison of venlafaxine and amitriptyline. Outpatients with DSM-IV major depression, a minimum score of 20 on the 21-item Hamilton Depression Rating Scale (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to venlafaxine or amitriptyline, both drugs titrated to a maximum of 150 mg/day until study day 15. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression severity scales. Data were evaluated on an intent-to-treat basis using the LOCF method. One hundred and 16 patients were randomized, and 115 were evaluated for efficacy. Both drugs showed efficacy in the treatment of depression with or without melancholia. No significant differences were noted between treatments for any efficacy parameter. However, significantly (p < 0.05) more patients in the amitriptyline group had at least one adverse event. These results should support the efficacy and tolerability of venlafaxine in comparison with amitriptyline for treating major depression with or without melancholia.     

A comparison of zopiclone and propiomazine as hypnotics in outpatients: A multicentre,double-blind,randomized, parallel-group comparison of zopiclone and propiomazine in insomniacs

Summary

In a double-blind, parallel-group study of 135 patients with a mean age of 60 years, zopiclone 5?mg was compared with propiomazine 25?mg. The patients rated their sleep in a diary. There were statistically significant differences in favour of zopiclone for nine out of 13 variables measuring subjective sleep quality and quantity. Concerning side-effects, bad taste was reported more frequently in the zopiclone group and restless legs in the propiomazine group.     

文拉法辛缓释剂治疗抑郁症的双盲、随机、平行对照、多中心临床研究

目的 :比较文拉法辛缓释剂与氟西汀治疗抑郁症的疗效及安全性。方法 :文拉法辛缓释剂组(文拉法辛组 ) 6 4例 ,年龄为 4 1a±s 13a ,氟西汀组6 3例 ,年龄为 4 2a± 12a。按双盲双模拟法文拉法辛组用量 75m·d- 1,qd或氟西汀组用量 2 0mg·d- 1,qd。共 6wk。疗效评定采用HAMD ,HAMA及CGI。安全性评价应用TESS、实验室检查及体检。结果 :经过 6wk治疗 ,文拉法辛组痊愈率 6 9% ,有效率为 83%。氟西汀组的痊愈率 5 9% ,有效率为 71% ,P >0 .0 5。另外 ,文拉法辛组的抗抑郁作用起效较快 ,对伴随的焦虑症状也有较好疗效。文拉法辛组不良反应轻 ,安全性好 ;常见不良反应有 :恶心、呕吐、口干及出汗等。结论 :文拉法辛缓释剂是一种安全而有效的抗抑郁药 ,病人对药物的耐受性及依从性好     

解郁汤与氟西汀治疗抑郁症的对比临床研究

目的 评价解郁汤治疗抑郁症的临床疗效和安全性.方法 96例符合CCMD-3诊断标准的抑郁症患者入组,随机分人解郁汤治疗组48例及氟西汀对照组48例,观察8周,使用汉密尔顿抑郁量表(24项版本)(HAMD)判断疗效,并记录不良反应.结果 85例完成试验(解郁汤组43例,对照组42例,分别脱落5例及6例),结果显示:在试验结束时,解郁汤组有效率为60%,与氟西汀对照组(65%)无显著差异(P＞0.05);解郁汤组HAMD减分(-10.56±3.95),氟西汀组HAMD减分(-11.82±3.82),两组比较无显著差异(P＞0.05);解郁汤组在治疗后第7d HAMD评分及因子分(焦虑、躯体症状及睡眠紊乱评分)与氟西汀组比较有显著差异(P＜0.05);两组均有较高的耐受性,多数不良反应为轻中度.结论 解郁汤治疗抑郁症有效,耐受性好,不良反应少,尤其适合于有明显焦虑和失眠的轻、中度抑郁症患者.     

Single-blind comparison of venlafaxine and nortriptyline in elderly major depression

The objective of this single-blind study was to compare the efficacy and safety of venlafaxine extended-release and nortriptyline in elderly patients with moderate to severe major depression. In- and out-patients (N=68) with unipolar major depression were randomized to receive 6-month treatment with either nortriptyline or venlafaxine. Outcomes of the two groups were compared using measures including the Hamilton Depression Rating Scale (HDRS) and the Newcastle Scale. Side effects were assessed with the UKU side-effect rating scale. Of the 34 venlafaxine-treated patients, 22 were remitters, 7 were nonremitters, and 5 dropped out. The intent-to-treat remission rate was 71% (22 of 31). Of the 34 who received nortriptyline, 21 were remitters, 7 were nonremitters, and 6 dropped out. The intent-to-treat remission rate was 70% (21 of 30). These results suggest that the remission rate with a therapeutic plasma level of nortriptyline is similar to the remission rate with a standard dose of venlafaxine in this group of elderly major depressed patients. No significant differences were observed between dropout rates in the two groups, but autonomic side-effects were significantly more frequent for nortriptyline than for venlafaxine. These results confirm the efficacy and safety of venlafaxine extended-release for treating elderly major depression.     

A randomized, single-blind, comparison of venlafaxine with paroxetine in elderly patients suffering from resistant depression

It is estimated that up to 45% of patients with depression do not have an adequate response to a first trial of antidepressant therapy with even higher reported rates for the elderly patients. To compare the efficacy and the tolerability of venlafaxine vs. paroxetine in elderly patients suffering from resistant major depression, who did not respond to at least two previous adequate trials of antidepressants. Patients entered an 8-week single-blind study. Patients were rated using the Clinical Global Impression Scale, Hamilton Rating Scale for Depression, and the Geriatric Depression Scale. Assessments were performed at baseline and on days 7, 14, 21, 28, 42 and 56. Side effects were recorded in a systemic manner. Thirty patients were included in the study, (17 women, 13 men; mean age=75.9 years, range: 68-83) and all had completed the 6-week trial. Mean dose of venlafaxine used was 165 mg/day (SD=73.8; range 75-300 mg). Mean dose of paroxetine used was 26 mg/day (SD=15.04; range 10-60 mg). Nine patients treated with venlafaxine (60%) and five patients treated with paroxetine (33%) remitted after 8 weeks of treatment. Four patients treated with venlafaxine and eight patients treated with paroxetine failed to respond. Significant improvement in Hamilton Rating Scale for Depression scores between baseline and endpoint were observed in both groups of patients. The mean Hamilton Rating Scale for Depression change for paroxetine was -12.5 and for venlafaxine -19.1 (P<0.05). The mean Geriatric Depression Scale change for paroxetine was -3.2 and for venlafaxine -6.0 (P<0.3). The mean Clinical Global Impression Scale change was -2.3 for paroxetine and -3.5 for venlafaxine (P<0.05). Venlafaxine was significantly superior to paroxetine on Clinical Global Impression Scale and Hamilton Rating Scale for Depression measures. Side effects were transient and did not differ between treatment groups. Elderly depressed patients resistant to previous treatments had responded to a trial of paroxetine or venlafaxine. Remission rates were higher for venlafaxine and tolerability was acceptable for both compounds.     

Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study

The primary endpoints in this study were the remission rates [final Hamilton Rating Scale for Anxiety (HAM-A) total score < or =7] and reduction from baseline in the HAM-A total score in patients with generalized anxiety disorder (GAD) and no associated depression. Patients with GAD (DSM-IV and HAM-A total score >18) were randomly assigned to treatment with venlafaxine XR or placebo for 8 weeks. A 1-week placebo run-in period preceded the double-blind phase. Patients with a >20% drop in their total HAM-A score during the run-in period, were excluded from the double-blind phase. All patients started therapy with 75 mg/day venlafaxine XR or matched placebo. Patients with less than 30% decrease in their HAM-A total score at the end of the second week, doubled their dose. Patients on the 150 mg/day dose underwent a 1-week taper period. Of the 24 patients in the venlafaxine XR group, 62.5% achieved remission versus 9.1% in the placebo group (P=0.0006). The mean decrease from baseline in HAM-A total score was 19.2 points for the venlafaxine XR group and 10.8 points for the placebo group (P<0.001). Eleven placebo-treated patients and seven venlafaxine XR treated patients doubled their dose at the end of the second week of double-blind treatment. No patient interrupted therapy because of side-effects. No changes in systolic or diastolic blood pressure were observed. Venlafaxine XR 75-150 mg/day was well tolerated. The remission rates achieved with venlafaxine 75-150 mg/day in non-depressed GAD patients were high with good tolerability.     

Adinazolam--a new antidepressant: findings of a placebo-controlled, double-blind study in outpatients with major depression

Adinazolam mesylate, a new triazolobenzodiazepine with antidepressant properties, was significantly superior to placebo based on the following efficacy measures: number of subjects who completed the study; number of subjects whose total score on the 21-item Hamilton Rating Scale for Depression (HAM-D) decreased by 50% or more; and number of subjects who reported that the drug helped them. Mean scores on three HAM-D clusters (anxiety/somatization, sleep disturbance, and an endogenomorphic cluster) also showed significant differences in favor of adinazolam. Side effects were generally mild and transient; however, a seizure of moderate intensity occurred during rapid tapering of adinazolam from 90 to 40 mg/day. There were no significant anticholinergic effects, and no mania or hypomania was reported in any subject. No consistently significant differences were observed between subjects whose primary diagnosis was major depression and those with a diagnosis of bipolar II depression.     

A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression

We examined the efficacy and tolerability of augmentation with an extended release formulation of methylphenidate (OROS MPH, Concerta) in patients with major depression who were nonresponders or partial responders to antidepressants. Sixty subjects with treatment-resistant depression (TRD) participated in a 4-week, randomized, double-blind, placebo-controlled study of augmentation with methylphenidate (18-54 mg/d). The preexisting antidepressant dose was unchanged. The primary efficacy measure was change in the 21-item Hamilton Depression Rating Scale from randomization to end of treatment. Data were analyzed with intent-to-treat with last observation carried forward approach. There were no statistically significant differences between the methylphenidate (n = 30) and placebo (n = 30) groups in reduction in 21-item Hamilton Depression Rating Scale scores (drug, -6.9; placebo, -4.7) from baseline to end of treatment (F1,47 = 1.24, P = 0.22), although responders were numerically higher in the extended-release methylphenidate group (40.0%) than in the placebo group (23.3%). On the secondary efficacy measures of changes in Clinical Global Impression-Improvement and Severity scores and Beck Depression Inventory-Second Edition, the drug failed to separate from placebo, although the proportion of responders in the drug group were numerically higher than placebo. There were no significant differences in weight, heart rate, and blood pressure changes between the 2 groups. The common adverse events were loss of appetite, nausea, headache, and anxiety. The mean dose of drug was 34.2 mg/d. The study did not demonstrate a statistically significant benefit for augmentation with methylphenidate in TRD. Combination of methylphenidate with antidepressants was well tolerated. Adequately powered, randomized, controlled trials are necessary to fully evaluate the efficacy of extended-release methylphenidate in TRD.     

盐酸文拉法辛缓释胶囊治疗青少年抑郁症对照研究

目的：评价盐酸文拉法辛缓释胶囊治疗抑郁症的疗效与安全性。方法：采用随机、双盲、双模拟、氟西汀平行对照研究。60例青少年抑郁症患者随机分为盐酸文拉法辛缓释胶囊组30例与氟西汀组30例,分别口服盐酸文拉法辛缓释胶囊150mg/d或氟西汀20mg/d,疗程8周。以汉密尔顿抑郁量表（HAMD）和临床疗效总评量表（CGI）为评估临床疗效的工具。结果：两组HAMD评分在治疗结束时较基线均显著减少（P〈0.01）;盐酸文拉法辛缓释胶囊组与氟西汀组有效率分别为70.0%与65.5%,差异无统计学意义（P〉0.05）。取Λ=0.1,α=0.05进行等效性检验,u=1.97,P〈0.05。盐酸文拉法辛缓释胶囊组常见的不良反应为恶心、头痛、失眠和食欲减退,发生率与氟西汀组差异无统计学意义（P〉0.05）。结论：两组药物不良反应发生率无统计学差异,盐酸文拉法辛缓释胶囊治疗青少年抑郁症和氟西汀一样有效。     

A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features

The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d). The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score. For trial 1, endpoint improvement for the OLZ group (-14.9) was not significantly different from the PLA or OFC groups. The OFC group had significantly greater endpoint improvement (-20.9) than the PLA group (-10.4, P = 0.001); this significant difference was present within 7 days of therapy and maintained at every subsequent visit. The OFC group also had significantly higher response rate (63.6%) than the PLA (28.0%, P = 0.004) or OLZ (34.9%, P = 0.027) groups. For trial 2, there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates. The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo. Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial; however, an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated.     

博乐欣与阿米替林治疗门诊抑郁症患者对照研究

目的比较博乐欣（文拉法辛）与阿米替林治疗门诊抑郁症的临床疗效和不良反应。方法对63例抑郁症患者随机分为两组,分别给予博乐欣和阿米替林治疗8周。采用汉密尔顿抑郁量表（HAMD）、药物不良反应量表（TESS）进行评临床疗效评定不良反应。结果博乐欣与阿米替林嗪显效率差异有显著性,博乐欣组显效快,不良反应少。结论博乐欣是一种安全有效的抗抑郁剂。     

文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效比较

目的 :比较文拉法辛与氯米帕明治疗抑郁症伴焦虑症状的疗效及安全性。方法 :文拉法辛组2 6例 ,用文拉法辛 50～ 2 0 0mg·d- 1,po ,bid～tid ;氯米帕明组 2 4例 ,用氯米帕明 50～ 2 0 0mg·d- 1,po ,bid～tid ;2组均以HAMD ,HAMA ,TESS评定观察 6wk。结果 :对抑郁症状的治疗 ,文拉法辛组与氯米帕明组显效率均为 84 % (P >0 .0 5) ;对伴随的焦虑症状的治疗 ,文拉法辛组显效率为 92 % ,氯米帕明组显效率为 63% (P <0 .0 5)。文拉法辛组常见不良反应为恶心 ( 2 7% )、口干 ( 19% )、便秘( 19% )、震颤 ( 12 % )、乏力 ( 8% )、头晕 ( 8% )等。结论 :文拉法辛治疗抑郁症伴焦虑症状的疗效肯定、耐受性良好 ,而且对焦虑症状的治疗效果优于氯米帕明     

A double-blind,randomized parallel-group,efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder

S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression. SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression.     

A double-blind comparison of sertraline and clomipramine in the treatment of major depressive disorder and associated anxiety in general practice

In this double-blind study in primary care patients, the efficacy and safety of sertraline, an antidepressant which is a selective inhibitor of serotonin re-uptake, was compared with clomipramine. Patients with DSM-III-defined major depression and with significant anxiety randomly received 50-150 mg of either sertraline (N=51) or clomipramine (N=55) once daily for 6 weeks. The mean final daily dose was 63.5 mg sertraline and 60.6 mg clomipramine. Seventy five percent of sertraline-treated and 79% of clomipramine-treated patients were maintained on the lowest dose of 50 mg once daily. The mean scores of all the rating scales (HAM-D, HAM-A, HAD, CGI) showed similar efficacy between the treatments in reducing the symptoms of depression and anxiety. Clomipramine was less well tolerated than sertraline with a greater overall incidence of side effects, or significantly greater incidence of anticholinergic side effects and significantly more patient withdrawals due to side effects; 18% in the clomipramine group compared with 4% in the sertraline group. The results indicate that sertraline is an effective agent to use in primary care patients with depression and associated symptoms of anxiety and is better tolerated than the tricyclic comparator clomipramine.