Preventive interventions for individuals at risk of developing bipolar disorder: A systematic review and meta-analysis

Background: This systematic review and meta-analysis aimed to explore whether early interventions can reduce affective symptoms and have long-term benefits among individuals at risk of bipolar disorder (BD). Methods: The PubMed, Embase, and Web of Science databases were searched. The primary outcome was continuous symptom scores before and after treatment. Random effects meta-analyses were conducted for each outcome arm studied and pooled mean difference estimates were calculated. Results: The search identified 10 controlled studies involving 425 participants and 6 single-arm studies involving 90 participants. For controlled trials, meta-analysis showed that the interventions led to greater reduction in clinical global score than placebo (standardized mean differences (SMD) = -0.96, 95 % CI:-1.32, -0.60), and supported a long-term longitudinal effect for pharmacotherapy (SMD = -0.42, 95 % CI: -0.79, -0.05). For single-arm trials, both pharmacotherapy and psychotherapy showed efficacy for depressive symptoms, while pharmacotherapy only showed efficacy for hypomania symptoms (effect size (ES) = -9.16, 95 % CI:-11.29, -7.04). Discontinuation of pharmacotherapy due to adverse effects did not show a difference. Limitations: The primary limitations are the small number of RCTs and the influence of medication dosage. Conclusions: Based on the limited available data, early interventions show efficacy for individuals at risk of BD. Psychological therapy might be more beneficial for depressive symptoms and have long-term benefits for hypomania. Pharmacotherapy may be appropriate in situations of severe hypomanic symptoms and the poor functioning. Large, well-designed, double-blind -controlled trials are needed to make solid conclusions about the efficacy of early interventions.