Lurasidone Versus Quetiapine for Bipolar Depression in Adolescents and Young Adults: A Randomized Non- Inferiority Trial

Abstract Background Treating bipolar depression in adolescents and young adults is challenging, and clinical trial evidence guiding its management—particularly in non-Western populations—remains limited. Although both lurasidone and quetiapine are used in this population, no head-to-head comparison has been conducted. This study therefore compared the efficacy and safety of the two agents in Chinese patients aged 14–24 years with bipolar depression. Methods This was a single-center, open-label, randomized non-inferiority trial with flexible dosing. Sixty patients were randomly assigned to receive 8 weeks of treatment with either lurasidone or quetiapine. The primary outcome was the change from baseline in MADRS total score at week 8. Secondary outcomes included treatment response, remission, anxiety symptoms, social functioning, and safety outcomes. Fifty-five patients were included in the primary analysis. Results Ultimately, 55 patients were included in the full analysis set. Both lurasidone and quetiapine significantly reduced MADRS total scores after 8 weeks of treatment. No significant between-group difference was observed in MADRS score changes at week 8 (mean difference = −4.38, 95% CI [−8.67, 2.24], P = 0.098) or at any follow-up time point, or in anxiety symptom improvement, social functioning, treatment response, or remission rates. Additional intention-to-treat and sensitivity analyses confirmed the robustness of the primary findings. The two drugs showed distinct adverse event profiles: lurasidone was associated with higher incidences of akathisia, parkinsonism, nausea, and anxiety, whereas quetiapine was associated with more frequent somnolence. No serious adverse events, clinically significant metabolic abnormalities, or manic switches occurred in either group, and suicide risk remained stable throughout the trial. Conclusions Lurasidone demonstrated efficacy comparable to that of quetiapine in Chinese adolescents and young adults with bipolar depression, with a distinct tolerability profile characterized by a lower sedative burden but higher rates of akathisia and parkinsonism. Given its lower sedative burden, lurasidone may be particularly suitable for students and young patients in educational or occupational settings, although further study is warranted. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100049426. Registered 02 August 2021. Ethics approval number: 2021(55h)-202199FS-2.