ReviewAntidepressant combination for major depression in incomplete responders—a systematic review
Introduction
Antidepressants are a mainstay of the treatment of major depression. However the overall treatment outcome of depressed patients is usually far from optimal. Regardless of the initial choice of antidepressant, 30–50% of patients with a major depressive episode will not respond satisfactorily to adequate standard treatment (Bauer et al., 2007). Remission rates vary from 42% to 46% (Casacalenda and Perry, 2002, Smith and Dempster, 2002) and about 30% of patients may not reach remission after multiple treatment trials (Rush et al., 2006). A review of four meta-analyses of efficacy trials submitted to the US Food and Drug Administration (FDA) suggests that antidepressants are only marginally efficacious compared with placebo and documents a profound publication bias that inflates their apparent efficacy (Pigott et al., 2010).
Antidepressant combination has been suggested as a strategy to increase treatment efficacy. There are two kinds of studies that evaluate antidepressant combination. One uses the combination from the beginning of treatment. We have published a systematic review and meta-analysis of this approach (Rocha et al., 2012). Another strategy is to add a second antidepressant to the treatment regimen of patients with persistent major depression despite adequate antidepressant monotherapy. However there are sparse data to support this strategy since the few trials that investigated this strategy have methodological flaws and involve small samples (Dodd and Horgan, 2005, El-Mallakh and Kaur, 2010, Rush, 2010, Thase, 2011). The larger studies about antidepressant combination in incomplete responders were conducted as part of the STAR⁎D trial but the lack of placebo control in these studies, among other drawbacks, prevents definite conclusions about the results. The objective of the present study was to perform a systematic review and meta-analysis of the combination of antidepressants versus a single antidepressant for the treatment of major depressive disorder with incomplete remission.
Section snippets
Material and methods
This systematic review was conducted at Instituto de Previdência dos Servidores do Estado de Minas Gerais, Faculdade da Saúde e Ecologia Humana, Faculdade de Medicina da Universidade Federal de Minas Gerais, and Faculdade de Ciências Médicas de Minas Gerais.
Studies were retrieved from the following sources: PubMed (1966 to February, 2012), Cochrane Library (until February, 2012), Excerpta Medica Database (Embase) (1980 to February, 2012), PsycINFO (1980 to February, 2012) and Literatura
Description of studies with potential for inclusion
Out of the 4,884 studies retrieved through the search strategy, 809 were excluded because they were duplicated records and 4,063 were excluded because they failed to meet the inclusion criteria (non-randomized controlled trials, narrative reviews, case reports, retrospective studies and studies not dealing with the clinical condition or intervention of interest). Twelve full-text studies were assessed for eligibility. Out of the 12 full-text studies, 7 were excluded due to several reasons. Four
Discussion
The results of this systematic review showed a paucity of studies evaluating antidepressant combination for depressed patients with incomplete response. There were only five studies with methodological differences and some methodological drawbacks involving a total of 565 patients (483, considering only the arms of interest). Only two small trials reported benefits with antidepressant combination (Ferreri and Lavergne, 2001, Carpenter and Yasmin, 2002). In both studies, the combination arm was
Role of funding source
The authors didn't receive support or grant of any funding body.
Conflict of interest
Fábio Lopes Rocha—Principal investigator in clinical trials (Current: AstraZeneca, Eli Lilly, Roche, and Servier; Past: Janssen Cilag, Pfizer)
Cíntia Fuzikawa—none
Rachel Riera—none
Melissa Guarieiro Ramos—none
Cláudia Hara—Sub-investigator in clinical trials (Current: AstraZeneca, Eli Lilly, Roche, and Servier; Past: Janssen Cilag, Pfizer)
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