A randomized, double-blind, parallel-group comparison of venlafaxine and clomipramine in outpatients with major depression

A multicentre, randomized, double-blind study was conducted to compare the safety and antidepressant efficacy of venlafaxine and clomipramine in 102 outpatients with major depression. The patients received either venlafaxine or clomipramine at a dose titrated from 50 mg to a maximum of 150 mg/day during the first 2 weeks of treatment. Treatment was continued for up to 43 days. Montgomery Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D) scores decreased significantly (p < or = 0.05) from baseline in each treatment group but were not significantly different between groups. Response rates on the MADRS and HAM-D were 62% and 59%, respectively, with venlafaxine and 54% and 43%, respectively, with clomipramine. Treatment-emergent study events were the primary reason for withdrawal in only 13% of venlafaxine-treated patients and 20% of clomipramine-treated patients. On questionnaires, the incidence of anticholinergic-type events was 60% with venlafaxine and 68% with clomipramine. However, significantly (p = 0.043) more patients in the clomipramine group reported multiple anticholinergic events than in the venlafaxine group. In the clomipramine group, mean ventricular heart rate increased significantly (p = 0.003) and mean systolic blood pressure decreased significantly (p = 0.028) from baseline, but no clinically significant electrocardiographic changes were observed. These results confirm the efficacy and safety of venlafaxine in the treatment of outpatients suffering from major depression.     

A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder

This was a 6-week, double-blind comparison of fluoxetine, imipramine, and placebo in 89 patients with bipolar depression. Using the criteria of greater than or equal to 50% improvement in the HAMD-total score after at least 3 weeks on study drug, endpoint analysis showed 86% of the fluoxetine-treated patients improved compared with 57% of the imipramine-treated and 38% of the placebo-treated patients. Significantly fewer fluoxetine-treated patients discontinued due to adverse events than did imipramine-treated patients (7% vs. 30%, respectively).     

A comparison of nefazodone, imipramine, and placebo in patients with moderate to severe depression

In this sample of moderately to severely depressed outpatients, nefazodone therapy proved superior to placebo. Nefazodone therapy was also associated with fewer dropouts from adverse effects than was imipramine. In view of these efficacy findings as well as the promising side effect and safety profile of nefazodone, further research is warranted to evaluate its therapeutic potential in the treatment of depressive illness.     

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.     

Effects of fluoxetine on the polysomnogram in outpatients with major depression.

This study investigated the effects of open-label fluoxetine (20 mg/d) on the polysomnogram (PSG) in depressed outpatients (n = 58) who were treated for 5 weeks, after which dose escalation was available (< or = 40 mg/d), based on clinical judgment. Thirty-six patients completed all 10 weeks of acute phase treatment and responded (HRS-D < or = 10). PSG assessments were conducted and subjective sleep evaluations were gathered at baseline and at weeks 1, 5, and 10. Of the 36 subjects who completed the acute phase, 17 were reevaluated after 30 weeks on continuation phase treatment and 13 after approximately 7 weeks (range 6-8 weeks) following medication discontinuation. Acute phase treatment in responders was associated with significant increases in REM latency, Stage 1 sleep, and REM density, as well as significant decreases in sleep efficiency, total REM sleep, and Stage 2 sleep. Conversely, subjective measures of sleep indicated a steady improvement during acute phase treatment. After fluoxetine was discontinued, total REM sleep and sleep efficiency were found to be increased as compared to baseline.     

A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness

One hundred and eighty three patients with DSM-III-R major depressive illness were allocated randomly to treatment with one of two new generation antidepressants, fluoxetine and lofepramine. Both patient groups had significantly lower mean scores on the Hamilton Depression Rating Scale (HDRS) 6 weeks after entry to the trial (p < 0.001), but there were no differences between the groups, either at baseline or after 6 weeks, in total HRDS score or in subscores for anxiety or suicidality. Anticholinergic side effects were commoner with lofepramine; adverse effects were on the whole mild and few patients dropped out because of them. This study does not support previous claims of specific adverse effects of fluoxetine on anxiety and suicidality.     

Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder

The aim of this study was to compare the efficacy and tolerability of reboxetine, a uniquely selective noradrenaline reuptake inhibitor, with the selective serotonin reuptake inhibitor, fluoxetine. A double-blind, randomized, parallel-group, multicentre design was employed. One hundred and sixty-eight patients with acute major depressive episodes were randomized to receive oral reboxetine (8-10 mg/day) or oral fluoxetine (20-40 mg/day). The treatment period was 8 weeks. Reboxetine and fluoxetine were similarly effective as assessed by the mean reduction in total Hamilton Depression Rating Scale score, the percentage of responders and patients in remission, Clinical Global Impression severity of illness and global improvement scores and Montgomery-Asberg Depression Rating Scale. A sub-analysis of patients with severe depression indicated that reboxetine had superior efficacy compared with fluoxetine. Both treatments resulted in some improvement in Social Adaptation Self-evaluation Scale total scores and this was more evident for those patients treated with reboxetine who achieved remission. Both treatments were well tolerated. The results indicate that reboxetine is an effective and well tolerated antidepressant, being more effective than fluoxetine in patients with severe depression, and more effective in terms of social functioning in those patients who achieved remission.     

Controlled comparison of milnacipran and fluoxetine in major depression

The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P=0.01) including five individual items, Hamilton depression scale (P=0.002) including ten individual items, CGI of severity (P=0.01) and therapeutical index (P=0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P=0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P=0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.     

A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression

Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression.     

A comparison of fluoxetine and amitriptyline in the treatment of major depression

Fluoxetine, a new serotonin uptake blocking antidepressant, was compared with amitriptyline in a double-blind study. Patients were diagnosed as having major depression, according to DSM-III criteria, when interviewed with the Diagnostic Interview Schedule. There was significant improvement in patient and observer ratings of depression in both groups, with no difference between groups. Recent memory improved significantly in the fluoxetine group but not in the amitriptyline group. Numbers of patients reporting side-effects were similar but the profiles of side-effects were different, with more patients on amitriptyline reporting anticholinergic and intolerable side-effects.     

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.     

Comparing the effects of fluoxetine and imipramine on total cholesterol, triglyceride, and weight in patients with major depression

Background

Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata.

Methods

The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection in immunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazole and itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns of the organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI). The potential gene(s) implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP). Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s) in resistant isolates as compared to sensitive and reference strains.

Results and conclusions

The aldo-keto-reductase superfamily (AKR gene) was upregulated in the resistant clinical isolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.     

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 double-blind controlled study of viloxazine and imipramine in depression

Summary

Fifty-nine depressed patients entered a double-blind, between patient comparison of viloxazine hydrochloride (300?mg./day expressed as base) and imipramine hydro-chloride (150?mg./day expressed as salt). Twenty-nine patients took viloxazine and 30 imipramine. Depression was assessed at weekly intervals, using the Hamilton Scale over a period of 6 weeks, and both drugs produced a statistically significant antidepressant effect. No difference emerged between the response to the two agents. Imipramine was associated with a significantly higher incidence of side-effects than viloxazine and they were more persistent. Imipramine produced a mean increase in weight over 6 weeks of 5.9 kg. whereas viloxazine produced a rise of only 2.4 kg. Viloxazine produced few anticholinergic side-effects; imipramine, on the other hand, was associated with frequent and persistent side-effects such as dry mouth, blurred vision, disturbed micturition and constipation. Drowsiness was not seen with viloxazine but was seen in over half the patients on imipramine. It is concluded that, whereas viloxazine has antidepressant properties equal to those of imipramine, it has a much lower incidence of side-effects, and what side-effects it does have are transient.     

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.     

Tianeptine and fluoxetine in major depression: a 6-week randomised double-blind study

In a 6-week, multicentre, randomised, double-blind controlled study, tianeptine (37.5 mg/day) and fluoxetine (20 mg/day) were compared for efficacy and safety in 178 patients with major depression. No significant difference was shown between the two drugs, either in terms of efficacy (MADRS, CGI, COVI) or in terms of safety, except for the CGI 'severity of illness' which was lower at the end point with tianeptine than with fluoxetine. The percentages of responders (as defined by a 50% decrease of the MADRS score from baseline to end point) were 75% with tianeptine and 67% with fluoxetine, showing the efficacy of both drugs. In conclusion, both tianeptine and fluoxetine are effective and well-tolerated treatments for major depression.     

Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety

The aim of this double-blind study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of patients with depression and anxiety. A total of 146 moderately depressed patients with associated anxiety were randomized to receive 75 mg/d venlafaxine or 20 mg/d fluoxetine for 12 wk. Dose increases were permitted after 2 wk of treatment, to 150 mg/d venlafaxine and 40 mg/d fluoxetine, to optimize response. At the final visit, a statistically significantly greater efficacy of venlafaxine over fluoxetine was observed on depressive symptoms and concomitant anxiety, and 75.0 and 50.7% of patients administered venlafaxine and fluoxetine, respectively, showed an overall response. A sustained response (for at least 2 wk), present at the end of the study was achieved in 57.8 and 43.3% of patients in the venlafaxine and fluoxetine groups, respectively, and at the final visit, 59.4 and 40.3% of patients, respectively, were in remission (virtually asymptomatic). Dose increases were required by a greater percentage of patients in the fluoxetine group (52.9%), than in the venlafaxine group (37.1%), and in those patients whose dose was increased, a higher efficacy was again observed with venlafaxine. Venlafaxine and fluoxetine were well tolerated, with the most frequently experienced adverse events being nausea and headache. Fewer patients in the venlafaxine group than in the fluoxetine group reported at least one adverse event (55.7 and 67.1% patients, respectively). Venlafaxine therefore proved to be significantly more effective than fluoxetine in improving depressive symptoms and concomitant anxiety.