Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis

Abstract

Introduction: Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common.

Areas covered: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in ≥ 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta-analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 – 1.10) and frequency of ≥ 1 AE (RR = 1.19, 95% CI = 0.95 – 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 – 2.38; sweating: RR = 1.95, 95% CI = 1.13 –3.38, ≥ 7% weight gain: RR = 3.15, 95% CI = 1.34 – 7.41; weight gain = 2.17, 95% CI = 0.71 – 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 – 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs.

Expert opinion: The potential for increased AEs with AD + AD co-treatment needs to be considered vis-à-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed.

Keywords:

• adverse effects
• antidepressant
• augmentation
• combination
• co-treatment
• depression
• major depressive disorder
• meta-analysis
• safety
• tolerability

Declaration of interest

CU Correll has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Actavis, Alkermes, Bristol-Myers Squibb, Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Reviva, Roche, Sunovion, Supernus and Takeda. He has received grant support from Bristol-Myers Squibb, Otsuka and Takeda. K Hagi is an employee of Dainippon Sumitomo Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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