Efficacy and safety of pharmacological and non-invasive brain stimulation for adolescent bipolar depression: a systematic review and network meta-analysis.

This network meta-analysis evaluates the efficacy and safety of pharmacological and physical treatments for depressive episodes in adolescents with bipolar disorder (BD), incorporating evidence from six randomized controlled trials (RCTs), total N = 879. Due to the absence of shared comparators, pharmacological treatments and non-invasive brain stimulation (NIBS) were analyzed in separate evidence networks rather than being directly compared.Pharmacological treatments included lurasidone, olanzapine-fluoxetine combination (OFC), and quetiapine, while NIBS consisted of transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS). P-scores probabilities showed lurasidone as the most effective for reducing depressive symptoms (CDRS-R SMD: -0.41, 95% CI: -0.62 to -0.19) and improving response rates (RR: 1.64, 95% CI: 1.30-2.04). OFC had the highest remission rates (RR: 1.39, 95% CI: 1.03-1.89). Quetiapine demonstrated limited antidepressant efficacy (CDRS-R SMD: -0.12, 95% CI: -0.38-0.15) but significantly reduced treatment-emergent mania risk (RR: 0.22, 95% CI: 0.05-0.97). In NIBS, tDCS outperformed both iTBS and placebo for reducing depressive (HAMD SMD: -2.56, 95% CI: -3.40 to -1.73) and anxiety symptoms (HAMA SMD: -3.21, 95% CI: -4.15 to -2.28). These results suggest that lurasidone and tDCS may be promising options for symptom management in adolescents with BD, while quetiapine may be considered for preventing manic switching. Further studies, including head-to-head trials, are needed to better understand the long-term effects and address gaps in suicide risk management and multimodal treatment strategies.