The results of an updated meta-analysis on the comparative benefits and harms of second-generation antidepressants in the treatment of major depressive disorder (MDD) have been published in the Annals of Internal Medicine.

The authors note that MDD affects over 16% of adults at some point in their lifetime, and the condition is associated with a high economic burden. Pharmacotherapy is the primary choice for its medical management, with second-generation antidepressants (e.g. selective serotonin reuptake inhibitors [SSRIs], serotonin and norephinephrine reuptake inhibitors, and related drugs) accounting for the majority of prescriptions.  Several previous systematic reviews have sought to compare the safety and efficacy of the available second-generation antidepressants, coming to differing conclusions.  The current article updates a previous review, including an assessment of effects in different patient subgroups.  

The authors conducted a search of PubMed, Embase, PsycINFO, the Cochrane Library, and International Pharmaceutical Abstracts from 1980 to August 2011, with additional search of a number of other sources to identify unpublished data.  For the assessment of efficacy, they sought head-to-head RCTs of at least 6 weeks’ duration comparing two drugs (placebo-controlled studies were included for indirect comparisons).  For harms, they examined data from both RCTs and observational studies (including at least 1000 patients, with follow-up of ≥12 weeks).

Meta-analyses of head-to-head comparisons were conducted if relevant data were available from at least three studies.  As many comparisons lack head-to-head data, mixed-treatment comparisons of head-to-head and placebo-controlled studies were conduced, using Bayesian methods.  The analysis included 234 studies (of which 118 were head-to-head), the majority of which were sponsored by pharmaceutical companies.

The authors report that overall, there were no substantial differences seen between the different second-generation antidepressants in efficacy for the treatment of acute, continuation or maintenance phases of MDD, or in any of the patient subgroups studied.  Although some of the comparisons were statistically significant, the authors comment that the absolute differences were small and unlikely to be clinically relevant.  Individual drugs do however differ with respect to adverse effects and onset of action and this may influence the choice for a particular patient.   

The authors discuss the limitations of their analysis, for example the bulk of the data were from efficacy studies with highly selected populations, the use of indirect comparisons (which have their own methodological limitations), and the possibility of publication bias.  They conclude that the existing evidence does not support the prescribing of a particular second-generation antidepressant first-line, or as a subsequent treatment in those who do not respond.  An informed decision should take into account the differences in adverse events, dosing regimen and onset of action, taking patient preferences into account.