Lumateperone 42 mg/d is effective in the treatment of schizophrenia and has no clinically significant effects on body weight, metabolic variables, motor function, the ECG QT interval, or prolactin levels, with a likelihood to be helped or harmed (LHH) much greater than 1 when comparing therapeutic response to these tolerability/safety outcomes. When comparing therapeutic response versus a somnolence/sedation AE, lumateperone appears to be associated with somnolence/sedation, and LHH approaches 1. In indirect comparisons with other antipsychotics, this somnolence/sedation AE profile is not dissimilar; however, the absence of weight gain, glucose/lipid abnormalities, and akathisia, as well as the absence of prolactin elevations, distinguishes lumateperone.