Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review.

Abstract

Lumateperone (LUM) is the U.S. Food and Drug Administration approvedatypical antipsychotic agent for adults with schizophrenia (SCZ) and bipolar depression (for both bipolar I and bipolar IIdisorder as as monotherapy or as adjunctive treatment to lithium or valproate). LUM simultaneously modulatesserotonin, dopamine, and glutamate neurotransmission. The foregoing pleiotropic mechanism of action is predictive oftherapeutic benefits across multiple domains of psychopathology in SCZ (i.e., positive, negative, cognitive, andprosocial symptoms). Herein, the overarching aim is to synthesize the extant literature reporting on the efficacy,safety, and tolerability of LUM in adults with SCZ. Four clinical studies (i.e., threeRCTs and one open-label trial) were included in this synthesis. Overall, LUM significantly reduced the severityof SCZ compared with placebo. The open label study provided the real-world effectiveness of shifting stable patientswith SCZ to LUM from other atypical antipsychotics. With respect to safety and tolerability profile, LUM demonstratedplacebo-level rates of weight gain, metabolic shift, prolactin elevation, extrapyramidal side effects (EPS), andakathisia across short term trials (i.e., 4-6 weeks). Taken together, our results indicatethat LUM significantly improves symptoms severity in adults with SCZ. LUM also exhibits a favorable tolerability andsafety profile with placebo level rates of weight gain, metabolic disruption, akathisia, extrapyramidal side effects(excluding akathisia), and prolactin elevation. Lumateperone should be conceptualized as a first-line treatmentstrategy for adults with SCZ.