Safety and tolerability of antipsychotic-mood stabilizer co-treatment in the management of acute bipolar disorder: results from a systematic review and exploratory meta-analysis

Abstract

Introduction: Mood stabilizer (MS) plus antipsychotic (AP) co-treatment is common in patients with acute bipolar disorder (BD), but adverse effects (AEs) of this strategy have not been systematically reviewed.

Areas covered: We conducted a systematic review searching PubMed/MEDLINE and PsycINFO on April 1, 2015 for randomized trials in ≥ 20 adults with acute manic/mixed or depressed BD comparing MS or AP monotherapy with their combination that reported quantitative AE data. Pooled together, MS+AP versus MS monotherapy (studies = 18, n = 4419) was associated with significantly higher burden regarding 21/53 (39.6%) individual AEs, particularly weight gain-related (5/5 = 100%), extrapyramidal (5/12 = 41.7%) and glucose/lipid-related AEs (3/8 = 37.5%). AP+MS versus AP monotherapy (studies = 3, n = 397) was associated with significantly higher burden regarding 4/21 (19.0%) individual AEs (≥ 1 AE, tremor, sedation/somnolence, vomiting).

Expert opinion: Efficacy advantages of AP+MS co-treatment versus monotherapy should be balanced with its greater AE burden. AE risk is higher for adding AP to MS (17 additional AEs) than adding MS to an AP, including the particularly concerning cardiometabolic AEs. More data are needed, as only one or two studies provided data for 21/21 (100%) AEs of MS augmentation of AP, and 13/53 (24.5%) AEs of AP augmentation of MS, and as sparse data suggest clinically relevant AE differences across individual AP+MS combinations.

Keywords:

• adverse effects
• antipsychotic
• augmentation
• bipolar disorder
• combination
• co-treatment
• meta-analysis
• mood stabilizer
• safety
• tolerability

Declaration of interest

CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, 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 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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