Maintenance Pharmacological Treatment of Juvenile Bipolar Disorder: Review and Meta-Analyses

Background: Guidelines for maintenance treatment of juvenile bipolar disorder rely heavily on evidence from adult studies and relatively brief trials in juveniles, leaving uncertainties about optimal long-term treatment. We aimed to systematically review long-term treatment trials for juvenile bipolar disorder. Methods: We analyzed data recovered by a systematic literature search using the PRISMA guidelines statement, through 2018, for peer-reviewed reports on pharmacological treatments for juvenile bipolar disorder lasting >= 24 weeks. Results: Of 13 reports with 16 trials of 9 treatments (18.8% were randomized and controlled), with 1773 subjects (94.4% BD-I; ages 6.9-15.1 years), lasting 11.7 (6-22) months. Pooled clinical response rates were 66.8% (CI: 64.4-69.1) with drugs vs 60.6% (53.0-66.7) in 3 placebo-control arms. Random-effects meta-analysis of 4 controlled trials yielded pooled odds ratio (OR) = 2.88 ([0.87-9.60], P = .08) for clinical response, and OR = 7.14 ([1.12-45.6], P = .04) for nonrecurrence. Apparent efficacy ranked: combined agents >anticonvulsants >= lithium >= antipsychotics. Factors favoring response ranked: more attention deficit/hyperactivity disorder, polytherapy, randomized controlled trial design, nonrecurrence vs response. Adverse events (incidence, 5.50%-28.5%) notably included cognitive dulling, weight-gain, and gastrointestinal symptoms; early dropout rates averaged 49.8%. Conclusions: Pharmacological treatments, including anticonvulsants, lithium, and second-generation antipsychotics, may reduce long-term morbidity in juvenile bipolar disorder. However, study number, quality, and effect magnitude were limited, leaving the status of scientific support for maintenance treatment for juvenile bipolar disorder inconclusive.