Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies

Abstract

Objective To systematically review published and unpublished efficacy studies of agomelatine in people with depression.Design Systematic review and meta-analysis. Eligibility criteria Double blind randomised placebo and comparator controlled trials of agomelatine in depression with standard depression rating scales. Data sourcesData synthesis Studies were pooled by using a random effects model with DerSimonian and Laird weights for comparisons with placebo and comparator antidepressant. The primary efficacy measure (change in rating scale score) was summarised with standardised mean difference (SMD; a measure of effect size) and secondary outcome measures with relative risks. All results were presented with 95% confidence intervals. Statistical heterogeneity was explored by visual inspection of funnel plots and by the I 2 statistic. Moderators of effect were explored by meta-regression. ResultsWe identified 20 trials with 7460 participants meeting inclusion criteria (11 in the published literature, four from the European Medicines Agency file, and five from the manufacturer). Almost all studies used the 17 item Hamilton depression rating scale (score 0-50). Agomelatine was significantly more effective than placebo with an effect size (SMD) of 0.24 (95% confidence interval 0.12 to 0.35) and relative risk of response 1.25 (1.11 to 1.4). Compared with other antidepressants, agomelatine showed equal efficacy (SMD 0.00, −0.09 to 0.10). Significant heterogeneity was uncovered in most analyses, though risk of bias was low. Published studies were more likely than unpublished studies to have results that suggested advantages for agomelatine. ConclusionsAgomelatine is an effective antidepressant with similar efficacy to standard antidepressants. Published trials generally had more favourable results than unpublished studies.

Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder

“…36 Among patients with severe depression, the SMD of 0.61 clearly separates SSRIs from placebo, and this can be considered a clinically important reduction in depressive symptoms, as measured by the HAM-D; however, this result is difficult to achieve with antidepressant treatment for MDD. 36,37 According to the previous metaanalyses of agomelatine, which was also recently approved for the treatment of MDD, the SMDs were 0.18-0.26 38,39 ; these results are similar to those of the present meta-analysis.…”

Vortioxetine: a review of efficacy, safety and tolerability with a focus on cognitive symptoms in major depressive disorder

“…In the first, vortioxetine was found to be superior in efficacy to agomelatine [30]. While these results are interesting, they are limited by the fact that agomelatine is not available in North America and is considered to be only a modestly effective agent [51]. More promising are the results from the second active comparator trial that demonstrated non-inferiority of vortioxetine versus venlafaxine, a commonly used SNRI [31].…”

Inflammation and the Silent Sequelae of Stroke

“…A variety of more traditional antiinflammatory therapies has also been used for the treatment of depression, including aspirin and other nonsteroidal antiinflammatory drugs, statins, and cytokine inhibitors like etanercept (which blocks TNF) [92][93][94][95]. Agomelatine is a a b c d member of a novel class of new antidepressants which are melatonin agonists; it has been approved by the European Union, after being shown to have similar efficacy to SSRIs for the treatment of depression [96,97]. Melatonin agonists have numerous effects on the immune system, most of which serve to limit inflammation [98].…”