Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors.

BACKGROUND: It had been suggested that the antidepressant venlafaxine, which inhibits reuptake of both serotonin and (at higher doses) noradrenaline, may result in better outcomes than treatment with selective serotonin reuptake inhibitors (SSRIs). AIMS: To compare remission rates during treatment with SSRIs or venlafaxine. METHOD: Data from eight comparable randomised, double-blind studies of major depressive disorder were pooled to compare remission rates (Hamilton Rating Scale for Depression score < or = 7) during treatment with venlafaxine (n = 851), SSRIs (fluoxetine, paroxetine, fluvoxamine; n = 748) or placebo (four studies; n = 446). RESULTS: Remission rates were: venlafaxine, 45% (382/851); SSRIs, 35% (260/748); placebo, 25% (110/446) (P: < 0.001; odds ratio for remission is 1.50 (1.3-1.9), favouring venlafaxine v. SSRIs). The difference between venlafaxine and the SSRIs was significant at week 2, whereas the difference between SSRIs and placebo reached significance at week 4. Results were not dependent on any one study or the definition of remission. CONCLUSIONS: Remission rates were significantly higher with venlafaxine than with an SSRI.

Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo.

BACKGROUND: Most examinations of the clinical efficacy of drugs used to treat depression pool subjects across gender and age groups. This investigation compared these patient subpopulations on the basis of remission and response rates associated with venlafaxine and selective serotonin reuptake inhibitor (SSRI) treatment. METHOD: A meta-analysis of original data from 8 comparable double-blind, active-controlled, randomized clinical trials (4 also placebo-controlled) was conducted. Antidepressant efficacy was assessed for patients (N = 2,045) aged 18 to 83 years (subgroups: < or = 40, 41-54, 55-64, and > or = 65 years) who met DSM-III-R criteria for major depression or DSM-IV criteria for major depressive disorder and were randomly assigned to receive venlafaxine (immediate release, N = 474; extended release, N = 377), one of several SSRIs (N = 748), or placebo (N = 446) for up to 8 weeks. Symptoms of depression were assessed using the Hamilton Rating Scale for Depression (HAM-D). Remission was defined as a HAM-D-17 score < or = 7, response was defined as > or = 50% decrease in HAM-D-21 score, and absence of depressed mood was defined as a HAM-D depressed mood item score of 0. RESULTS: We detected no significant age-by-treatment, gender-by-treatment, or age-by-gender-by-treatment interactions; men and women of different ages within a given antidepressant treatment group exhibited similar rates of remission, response, and absence of depressed mood. Regardless of age or gender, remission rates during venlafaxine therapy were significantly higher than during SSRI therapy (remission rates at week 8: venlafaxine, 40%-55% vs. SSRI, 31%-37%; p < .05). Regardless of patient age or gender, onset of remission was more rapid with venlafaxine than with SSRI treatment. By contrast, rates of absence of depressed mood with venlafaxine (34%-42%) and SSRIs (31%-37%) did not differ significantly and tended to be similar for all patient subgroups. CONCLUSION: These data suggest that men and women have comparable responses to SSRIs and venlafaxine across various age groups. Moreover, patients exhibited a more rapid onset and a greater likelihood of remission with venlafaxine therapy than with SSRI therapy regardless of age or gender.

Efficacy of once-daily venlafaxine extended release (XR) for symptoms of anxiety in depressed outpatients.

The effects of once-daily venlafaxine extended release (XR) 75-225 mg/day on symptoms of anxiety in depressed outpatients were assessed in two randomized, double-blind, placebo-controlled trials. In study 1, venlafaxine XR was significantly (p < or = 0.05) more effective than placebo by week 4 in relieving anxiety symptoms among patients with moderate or greater anxiety (anxiety-psychic item score > or = 2) at baseline. Among patients with severe (anxiety-psychic item score > or = 3) anxiety, venlafaxine XR was significantly (p < or = 0.05) more effective than placebo beginning at week 6. In study 2, among patients with moderate or greater anxiety (score > or = 2) at baseline, a significant reduction (p < or = 0.05- < or = 0.001) in HAM-D anxiety-psychic item scores was noted with venlafaxine XR compared with placebo from weeks 1 to 8. Among patients with severe anxiety (score > or = 3) at baseline, venlafaxine XR produced a significant reduction (p < or = 0.05- < or = 0.001) in the anxiety-psychic item score compared with placebo from weeks 1 to 8. Discontinuation for adverse events occurred in 11% of patients on venlafaxine XR, and the most common adverse events were nausea, dizziness, insomnia, somnolence and dry mouth. These results indicate that once-daily venlafaxine XR is effective for the treatment of anxiety symptoms associated with major depression in doses ranging from 75 to 225 mg/day.

Efficacy of venlafaxine and placebo during long-term treatment of depression: a pooled analysis of relapse rates.

The objective of this analysis was to determine the efficacy of venlafaxine in comparison with that of placebo during long-term treatment. A pooled analysis of relapse rates in outpatients with major depression continuing long-term treatment (up to 12 months) after responding to short-term treatment (6 weeks) was performed combining the data from four randomized, double-blind, placebo-controlled clinical trials. Relapses were defined as two consecutive Clinical Global Impression (CGI) severity scores greater than 3 (mildly ill), as a CGI severity score greater than 3 at withdrawal regardless of the reason for withdrawal, or as withdrawal due to lack of efficacy. Data from 304 patients (185 venlafaxine, 119 placebo) well balanced for baseline characteristics were included in the pooled analysis. Percentages of patients completing the long-term phase were 38% venlafaxine and 26% placebo (p = 0.034). Cumulative relapse rates by 6 months of long-term treatment were 11% venlafaxine and 23% placebo (p = 0.019). Cumulative relapse curves for the venlafaxine and placebo groups over the 1-year long-term treatment differed significantly (p = 0.022). The results from this analysis indicate that long-term treatment with venlafaxine in patients with major depressive disorder is effective in maintaining the initial response compared with placebo and suggest that venlafaxine will be effective in the prevention of relapse.

Comparing speeds of effectiveness of two treatments.

A variety of methods have been proposed for analyzing and summarizing data from clinical trials of pharmaceutical agents. Methods directed at evaluating the speed of activity of an agent are an important component of such analyses. We review several parameters that are useful for comparing speed of effectiveness and demonstrate their utility, both with didactic examples and with real data. The "survival function" is well suited to evaluating speed of cure, particularly when there is a fraction of the population that does not respond to a particular treatment. Some conditional parameters, such as the survival function among those who are curable, are shown to be inappropriate for the comparison of speeds of cure because they summarize speed of activity in different, and therefore noncomparable, populations. Comparisons based on these conditional survival curves are inappropriate and can lead to the wrong interpretation even when one treatment completely dominates another with respect to speed and efficacy. Methods appropriate for determining an optimal sequence of treatments are briefly reviewed. Examples from the published literature, as well as data from a recent study of venlafaxine, are used to demonstrate both appropriate and flawed interpretations of clinical trial data.

Effectiveness of venlafaxine treatment in a broad spectrum of depressed patients: a meta-analysis.

The effectiveness of the novel antidepressant venlafaxine was assessed in various subpopulations of depressed patients. Data from six comparable placebo-controlled, double-blind studies were pooled and analyzed (venlafaxine, n = 930; placebo, n = 500). Outcome variables were the Hamilton Rating Scale for Depression total score, Montgomery-Asberg Depression Rating Scale total score, and Clinical Global Impressions severity scores. Venlafaxine had notable antidepressant results in depressed patients regardless of age (although no age differences were apparent, too few patients over age 65 had been enrolled in the six studies to permit definitive conclusions), gender, presence of melancholia, and severity or duration of depression. Our analysis indicates that venlafaxine treatment is effective in a broad range of depressed patients.

Venlafaxine: measuring the onset of antidepressant action.

Venlafaxine, a new antidepressant, inhibits reuptake of norepinephrine and serotonin without appreciable effects on histaminergic, alpha-adrenergic, or cholinergic systems. Pharmacologically the drug is unique: the half-life is short and it exerts both rapid and prolonged beta-adrenergic desensitization after single doses in a rodent model. Venlafaxine has been thought to possess a rapid onset of clinical antidepressant action. Accordingly, two clinical studies in which moderate amounts of venlafaxine were given aggressively were reviewed to examine aspects of the drug's onset of action. Three statistical methodologies were employed--traditional analysis of depression scale scores, pattern analysis based on timing and persistence of response, and survival analysis of sustained response. All three methods showed venlafaxine to have significant effects early in the course of therapy. In addition, venlafaxine is the first drug to meet criteria for early onset using the pattern analysis methodology. Depressed patients aggressively treated with venlafaxine show significant benefit on or before Day 7 of treatment using traditional methods of analysis as well as survival analysis of sustained response.

Cumulative mean change procedure: application to a comparative trial of venlafaxine, imipramine, and placebo in the treatment of major depression.

1. A simple summary measure--namely, cumulative mean change (CMC)--is proposed for analyzing incomplete repeated measures in clinical settings. 2. A simple test statistic that uses the correlation between subject responses was derived and applied to a study comparing an investigational antidepressant, venlafaxine, with imipramine and placebo. 3. The global fashion in which CMC captured all data confirmed the efficacy advantage of venlafaxine over the two control agents.