Muhammad Youshay Jawad1,2, Yazen Alnefeesi1, Felicia Ceban1,2, Leanna M W Lui1, Saja Jaberi1, Joshua D Di Vincenzo1,3, Leila Amirbeik1, David C J Chen-Li1, Kayla Teopiz1, Lee Phan1, Bing Cao4, Roger Ho5,6, Joshua D Rosenblat1,7, Roger S McIntyre8,9,10,11. 1. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. 2. Brain and Cognition Discovery Foundation, Toronto, ON, Canada. 3. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. 4. Key Laboratory of Cognition and Personality (SWU), Faculty of Psychology, Ministry of Education, Southwest University, 400715, Chongqing, People's Republic of China. 5. Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 6. Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore. 7. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 8. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. roger.mcintyre@bcdf.org. 9. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. roger.mcintyre@bcdf.org. 10. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. roger.mcintyre@bcdf.org. 11. Brain and Cognition Discovery Foundation, Toronto, ON, Canada. roger.mcintyre@bcdf.org.
Abstract
PURPOSE OF REVIEW: Lumateperone (LUM) is the U.S. Food and Drug Administration approved atypical antipsychotic agent for adults with schizophrenia (SCZ) and bipolar depression (for both bipolar I and bipolar II disorder as as monotherapy or as adjunctive treatment to lithium or valproate). LUM simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. The foregoing pleiotropic mechanism of action is predictive of therapeutic benefits across multiple domains of psychopathology in SCZ (i.e., positive, negative, cognitive, and prosocial symptoms). Herein, the overarching aim is to synthesize the extant literature reporting on the efficacy, safety, and tolerability of LUM in adults with SCZ. RECENT FINDINGS: Four clinical studies (i.e., three RCTs and one open-label trial) were included in this synthesis. Overall, LUM significantly reduced the severity of SCZ compared with placebo. The open label study provided the real-world effectiveness of shifting stable patients with SCZ to LUM from other atypical antipsychotics. With respect to safety and tolerability profile, LUM demonstrated placebo-level rates of weight gain, metabolic shift, prolactin elevation, extrapyramidal side effects (EPS), and akathisia across short term trials (i.e., 4-6 weeks). Taken together, our results indicate that LUM significantly improves symptoms severity in adults with SCZ. LUM also exhibits a favorable tolerability and safety 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 treatment strategy for adults with SCZ.
PURPOSE OF REVIEW: Lumateperone (LUM) is the U.S. Food and Drug Administration approved atypical antipsychotic agent for adults with schizophrenia (SCZ) and bipolar depression (for both bipolar I and bipolar II disorder as as monotherapy or as adjunctive treatment to lithium or valproate). LUM simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. The foregoing pleiotropic mechanism of action is predictive of therapeutic benefits across multiple domains of psychopathology in SCZ (i.e., positive, negative, cognitive, and prosocial symptoms). Herein, the overarching aim is to synthesize the extant literature reporting on the efficacy, safety, and tolerability of LUM in adults with SCZ. RECENT FINDINGS: Four clinical studies (i.e., three RCTs and one open-label trial) were included in this synthesis. Overall, LUM significantly reduced the severity of SCZ compared with placebo. The open label study provided the real-world effectiveness of shifting stable patients with SCZ to LUM from other atypical antipsychotics. With respect to safety and tolerability profile, LUM demonstrated placebo-level rates of weight gain, metabolic shift, prolactin elevation, extrapyramidal side effects (EPS), and akathisia across short term trials (i.e., 4-6 weeks). Taken together, our results indicate that LUM significantly improves symptoms severity in adults with SCZ. LUM also exhibits a favorable tolerability and safety 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 treatment strategy for adults with SCZ.