Factors associated with increased risk of lurasidone-induced somnolence: Two case-control studies based on one bioequivalence trial in healthy volunteers.

Somnolence is a common adverse effect of antipsychotic drugs used to treat psychotic disorders. It causes problems in many areas of life, such as gainful employment, driving, childcare, and social interactions. Somnolence is a major problem for a relatively new antipsychotic drug, lurasidone, whose dose-effect relationship remains unclear. Based on data from a bioequivalence study of two 40 mg lurasidone hydrochloride tablets, we designed two case-control studies to explore the correlation between somnolence and exposure to lurasidone and determine the factors associated with lurasidone-induced somnolence. In the first case-control study, lurasidone was administered to healthy volunteers; 30 experienced somnolence (as pre-defined) but 29 did not. Moreover, plasma concentration at 1 h was significantly associated with somnolence (OR = 1.124; p = 0.001). In the second case-control study, 48 volunteers administered lurasidone were classified into somnolence and no-somnolence groups based on different time-related criteria. We observed a positive association between plasma concentration at 0.75 h and somnolence (OR = 1.024; p = 0.002). Receiver operating characteristic analysis revealed that a plasma lurasidone concentration >21.65 ng/mL 1 h after administration strongly predicted somnolence. Our findings in healthy volunteers need to be further validated in patients in clinical settings to determine the optimal dose and duration of lurasidone administration.