Lumateperone for the Treatment of Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed

To describe lumateperone for the treatment of schizophrenia in adults using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Data were obtained from the 3 phase 2/3 lumateperone trials, conducted between 2011 and 2016, in patients with schizophrenia diagnosed using the , Fourth Edition, Text Revision, or Fifth Edition. Efficacy was assessed using various response criteria; tolerability was principally assessed using rates of adverse events (AEs). Pooled data of the 2 informative studies showed statistically significant estimates of NNT versus placebo for lumateperone 42 mg/d for the responder thresholds of ≥ 20% and ≥ 30% improvement on Positive and Negative Syndrome Scale (PANSS) total scores, with NNT for response versus placebo at 4 weeks and endpoint of 9 (95% confidence interval [CI], 5-36) and 8 (95% CI, 5-21), respectively. Pooling all studies, discontinuation because of AEs was uncommon, and the NNH versus placebo was 389 (not statistically significant from placebo [NS]). Rates of individual AEs resulted in NNH versus placebo \u3e 10 except for somnolence/sedation (NNH of 8; 95% CI, 6-12). The occurrence of weight gain ≥ 7% from baseline yielded a NNH estimate of 122 (NS). Rates of akathisia were lower for patients receiving lumateperone compared with placebo. LHH for response versus somnolence/sedation was ~ 1 for lumateperone (similar to the risperidone active control group); otherwise, lumateperone exhibited LHH ratios that were much greater than 1 for all other AEs and that ranged from 13.6 to 48.6 for these other benefit-risk calculations. In 3 phase 2/3 trials, the benefit-risk assessment of lumateperone was favorable as measured by NNT, NNH, and LHH. ClinicalTrials.gov identifiers: NCT01499563, NCT02282761, NCT02469155