Body weight changes after switching to lurasidone for antipsychotic-induced weight gain in bipolar disorder: a multicenter retrospective study of a selected follow-up cohort

Abstract Background Antipsychotic-induced weight gain can undermine long-term treatment adherence and cardiometabolic health in bipolar disorder. Lurasidone has a relatively weight-sparing profile and efficacy in bipolar depression, but real-world data are limited for patients switched to lurasidone because of weight gain during prior antipsychotic treatment. Methods BK-LUD-I01 was a multicenter retrospective observational study conducted at 12 outpatient psychiatric clinics in Korea. Eligible patients were adults with bipolar disorder who had received stable aripiprazole, quetiapine, or olanzapine for at least 8 weeks, were switched to lurasidone because of antipsychotic-induced weight gain, and had 16 weeks of follow-up after switching. Patients who discontinued lurasidone or completely switched to another antipsychotic within the first 8 weeks were excluded. The primary endpoint was change in body weight from baseline to 16 weeks in the Full Analysis Set and was analyzed using the Wilcoxon signed-rank test. Secondary outcomes included body mass index, psychiatric rating scales, and safety. Results The Full Analysis Set included 155 patients; 129 (83.2%) had switched from aripiprazole, 21 (13.6%) from quetiapine, and 5 (3.2%) from olanzapine. Mean body weight decreased from 74.49 to 72.43 kg at 16 weeks (mean change − 2.06 kg, 95% confidence interval − 2.50 to − 1.62; median − 2.0 kg, interquartile range − 3.0 to − 0.75; p < 0.0001). In exploratory secondary analyses, body mass index decreased from 27.03 to 26.28 kg/m² ( p < 0.0001), and mean changes in Hamilton Depression Rating Scale total and Clinical Global Impression-Severity scores were − 5.36 and − 0.80 points, respectively, at 16 weeks (both p < 0.0001). In a post hoc descriptive analysis, 40 patients (25.8%) achieved at least 5% weight reduction. Weight decreases were observed across prior antipsychotic subgroups, including patients switched from aripiprazole. Treatment-emergent adverse events were recorded in 5 patients (3.2%); all were mild. Conclusions In this selected 16-week follow-up cohort of Korean adults with bipolar disorder switched to lurasidone because of antipsychotic-induced weight gain, reductions were observed in body weight, body mass index, depressive symptom severity, and global illness severity, with few recorded adverse events. These descriptive post-switch trajectories warrant prospective controlled evaluation.