Mood Stabilizers and Antipsychotics for Acute Mania: A Systematic Review and Meta-Analysis of Combination/Augmentation Therapy Versus Monotherapy

• Published in: CNS drugs 2014-11, Vol.28 (11), p.989-1003
• Main Authors: Ogawa, Yusuke, Tajika, Aran, Takeshima, Nozomi, Hayasaka, Yu, Furukawa, Toshi A.
• Format: Article
• Language: English
• Subjects: Acute Disease; Antimanic Agents - administration & dosage; Antimanic Agents - adverse effects; Antimanic Agents - therapeutic use; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Bias; Bipolar disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - psychology; Drug therapy; Drug Therapy, Combination; Humans; Medicine; Medicine & Public Health; Neurology; Neurosciences; Pharmacotherapy; Psychiatry; Psychopharmacology; Psychotropic drugs; Studies; Systematic Review; Teenagers; Treatment Outcome
• ISSN: 1172-7047; 1179-1934
• DOI: 10.1007/s40263-014-0197-8

Background Pharmacotherapy remains the mainstay of treatment for acute bipolar mania, but there are many choices, including mood stabilizers (MSs) and antipsychotics (APs). Objective To provide an up-to-date and comprehensive review of the efficacy, acceptability and adverse effects of MSs and APs as combination or augmentation therapy versus monotherapy with either drug class for the treatment of acute mania. Data Sources The Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, Scopus, and clinical trial databases were searched for articles published between the inception of the databases and July 1, 2014. The following keywords were used: [ bipolar disorder , mania , manic, mixed bipolar , schizoaffective ] combined with the names of MSs and APs. The reference lists of all the identified randomized controlled trials (RCTs), articles that cited the identified trials, and recent systematic reviews were also checked. Study Selection Double-blind RCTs comparing MS and AP as combination or augmentation therapy with either monotherapy during the acute phase treatment of mania were included in the present study. The electronic search yielded 6,445 potential articles in September 2013 and 264 new references in an updated search performed in July 2014. Finally, 19 RCTs were considered eligible for our meta-analyses: MS plus AP combination or augmentation therapy was compared with MS monotherapy in 14 trials ( n  = 3,651) and with AP monotherapy in 6 trials ( n  = 606) [one study compared combination therapy versus both MS monotherapy and AP monotherapy]. Data Extraction The primary outcomes were the mean change scores on validated rating scales for mania and all-cause discontinuation at 3 weeks. The secondary outcomes included response, remission, the mean change scores for depression, dropouts due to adverse events and to inefficacy, and adverse events at 3 weeks and mean change scores on validated rating scales at 1 week. Using random-effects models, standardized mean difference (SMD), risk ratio (RR) and numbers needed to treat with their 95 % confidence intervals (CIs) were calculated. Results Most patients included in trials comparing combination/augmentation therapy versus MS monotherapy had prior treatment with an MS, while more than 70 % of participants in trials comparing combination/augmentation therapy versus AP monotherapy had not been on medications or were washed out from their previous medication before randomization. MS plus AP combi