title: 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: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System , Glen Oaks, New York , USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Galling
authors.forename: Maryam A
authors.initials: MA
authors.lastname: Garcia
authors.forename: Uzoma
authors.initials: U
authors.lastname: Osuchukwu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hagi
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000208:Acute Disease; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents
keywords: adverse effects; antipsychotic; augmentation; bipolar disorder; co-treatment; combination; meta-analysis; mood stabilizer; safety; tolerability