In Reply We thank Gouse et al for raising 2 points regarding the efficacy and safety of lumateperone.1 The effect size of −0.30 for lumateperone, 42 mg, on the Positive and Negative Syndrome Scale total score is in the range of other recently approved antipsychotics: brexpiprazole (−0.26), cariprazine (−0.34), and lurasidone (−0.36).2 More recent trials of antipsychotics2,3 had higher placebo responses and therefore smaller effect size but not necessarily smaller improvement, which is what the patient and clinician would detect. Evaluated side by side in a separate study,4 lumateperone, 42 mg, and risperidone, 4 mg, a commonly used dose of a frequently prescribed antipsychotic, showed the same effect size of −0.4. The least-squares mean improvement from baseline in the Positive and Negative Syndrome Scale total score for lumateperone was similar in both studies (−14.5 in the current study1 vs −13.2 in the previous study4); only the placebo response differed (−10.3 in the current study1 vs −7.4 in the previous study4).