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Objective: Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and venlafaxine, and at analysing a potential influence of the investigated drugs on the placebo response. Method: We conducted a comprehensive systematic review and meta‐analysis of placebo‐controlled, double‐blind RCTs, which examined the efficacy of duloxetine and venlafaxine in the acute treatment of major depressive disorder. Results: We included 71 studies (29 duloxetine trials and 43 venlafaxine trials; one study provided data for the duloxetine and the venlafaxine data set). The placebo effect sizes, defined as pre‐postscore change divided by baseline standard deviation, differed significantly between venlafaxine and duloxetine studies (−2.51 vs. −2.09; test for subgroup differences P = 0.028; high heterogeneity). The analysis of effect modifiers and the metaregression analyses confirmed the drug, next to baseline depression severity and publication status, as the most influential independent predictor. Conclusion: Our analyses show a significant difference in the placebo response between venlafaxine and duloxetine trials and suggest that the investigated drug has an influence on the placebo response that is not related to baseline severity, changes over the years or other variables we included. [ABSTRACT FROM AUTHOR]

Schueler Y-B, Koesters M, Wieseler B, Grouven U, Kromp M, Kerekes MF, Kreis J, Kaiser T, Becker T, Weinmann S. A systematic review of duloxetine and venlafaxine in major depression, including unpublished data. To determine the short-term antidepressant efficacy and tolerability of duloxetine and venlafaxine vs. each other, placebo, selective serotonin reuptake inhibitors (SSRIs), and tri- and tetracyclic antidepressants (TCAs) in adults with major depression. Meta-analysis of randomised controlled trials identified through bibliographical databases and other sources, including unpublished manufacturer reports. Fifty-four studies including venlafaxine arms ( n = 12 816), 14 including duloxetine arms ( n = 4528), and two direct comparisons ( n = 836) were analysed. Twenty-three studies were previously unpublished. In the meta-analysis, both duloxetine and venlafaxine showed superior efficacy (higher remission and response rates) and inferior tolerability (higher discontinuation rates due to adverse events) to placebo. Venlafaxine had superior efficacy in response rates but inferior tolerability to SSRIs (OR = 1.20, 95% CI 1.07-1.35 and 1.38, 95% CI 1.15-1.66, respectively), and no differences in efficacy and tolerability to TCAs. Duloxetine did not show any advantages over other antidepressants and was less well tolerated than SSRIs and venlafaxine (OR = 1.53, 95% CI 1.10-2.13 and OR 1.79, 95% CI 1.16-2.78, respectively). Rather than being a first-line option, venlafaxine appears to be a valid alternative in patients who do not tolerate or respond to SSRIs or TCAs. Duloxetine does not seem to be indicated as a first-line treatment. [ABSTRACT FROM AUTHOR]

Guidelines for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults advocate methylphenidate as first-line treatment. The aim of this study was to review the effectiveness of methylphenidate treatment of adult ADHD and to examine the influence of methods on meta-analytic results. Electronic databases were searched to identify clinical trials comparing methylphenidate with placebo in the treatment of adult ADHD. Studies were summarised with meta-analytic methods. Subgroup analyses were conducted with respect to parallel group versus cross-over trials and self versus observer ratings. The relationship between dosage and effect size was explored by weighted regression analysis. The results were tested for publication bias, and several sensitivity analyses were performed. Findings and methods were compared with a previous meta-analysis. Eighteen studies met the inclusion criteria of which 16 were included in the meta-analysis. The overall effect size (d = 0.42) was significantly different from zero, but was only half the size expected on the basis of a previous meta-analysis. No significant differences could be observed in the subgroup analyses. The regression analysis showed no significant influence of mean daily dose on effect size. These results contradict findings of a previous meta-analysis and challenge guideline recommendations. Methodological issues in meta-analyses are discussed. [ABSTRACT FROM AUTHOR]