Efficacy and safety of pharmacological interventions for the maintenance of bipolar disorder: A systematic review and dose-related network meta-analysis across different age groups.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 41985753 · doi:10.1016/j.jad.2026.121798
What was done
A systematic review and dose-related network meta-analysis of randomized controlled trials (searched through January 12, 2026 across PubMed/MEDLINE, Embase, Web of Science, and Scopus) evaluated pharmacological maintenance therapies versus each other or placebo in bipolar disorder across age groups. Co-primary outcomes were relapse into an acute mood episode of any polarity and tolerability (discontinuation due to side effects). Secondary outcomes included polarity-specific relapse rates (depressive, manic, mixed), all-cause discontinuation (acceptability), and specific adverse events. Certainty was evaluated using the Confidence-In-Network-Meta-Analysis framework.
What was found
Across 44 RCTs covering 23 treatment combinations and 10,867 participants, sensitivity analyses restricting to low risk-of-bias trials and excluding effect-modifier outliers found that several specific regimens outperformed placebo: asenapine (20 mg/day), aripiprazole (20 mg/day, 30 mg/day), quetiapine (300, 550, and 600 mg/day), lithium (800 mg/day), lurasidone (80 mg/day), carbamazepine (400 and 650 mg/day), valproate (71–125 µg/mL), olanzapine (20 mg/day), long-acting injectable aripiprazole (400 mg/4 weeks), long-acting risperidone (25 mg/2 weeks), and combination aripiprazole 30 mg/day plus lamotrigine 200 mg/day. Numerical point estimates and confidence intervals for efficacy and tolerability outcomes were not reported in the abstract.
Why it matters
This review provides dose-specific comparative evidence across multiple classes of maintenance pharmacotherapy in bipolar disorder, supporting granular dosing decisions for long-term relapse prevention.
Limits
Numerical effect estimates, confidence intervals, tolerability rates, and age-group breakdown statistics were not reported in the abstract. Several drugs could not be reliably evaluated without outlier exclusion due to baseline imbalances across trials in participant age, sex ratios, BD-I versus BD-II subtypes, baseline episode severity, and study duration.
Cited by
- supports The anti-seizure medications lamotrigine, valproate, and carbamazepine are used to treat bipolar disorder.