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

  • Schizophrenia and Other Psychotic Disorders (AK Pandurangi, Section Editor)
  • Published:
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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).

Summary

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.

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Authors and Affiliations

  1. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada

    Muhammad Youshay Jawad, Yazen Alnefeesi, Felicia Ceban, Leanna M. W. Lui, Saja Jaberi, Joshua D. Di Vincenzo, Leila Amirbeik, David C. J. Chen-Li, Kayla Teopiz, Lee Phan, Joshua D. Rosenblat & Roger S. McIntyre

  2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Joshua D. Rosenblat & Roger S. McIntyre

  3. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Joshua D. Di Vincenzo & Roger S. McIntyre

  4. Brain and Cognition Discovery Foundation, Toronto, ON, Canada

    Muhammad Youshay Jawad, Felicia Ceban & Roger S. McIntyre

  5. Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Roger Ho

  6. Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore

    Roger Ho

  7. Key Laboratory of Cognition and Personality (SWU), Faculty of Psychology, Ministry of Education, Southwest University, 400715, Chongqing, People’s Republic of China

    Bing Cao

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  1. Muhammad Youshay Jawad
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Correspondence to Roger S. McIntyre.

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Conflict of Interest

Muhammad Youshay Jawad, Yazen Alnefeesi, Felicia Ceban, Saja Jaberi, Leila Amirbeik, Lee Phan, Bing Cao, and Roger Ho each declare no potential conflicts of interest. Roger McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Leanna M.W. Lui is a contractor Braxia Scientific Corp. Joshua D. Rosenblat is the medical director of the Braxia Health (formally known as the Canadian Rapid Treatment Center of Excellence and is a fully owned subsidiary of Braxia Scientific Corp) which provides ketamine and esketamine treatment for depression; he has received research grant support from the American Psychiatric Association, the American Society of Psychopharmacology, the Canadian Cancer Society, the Canadian Psychiatric Association, the Joseph M. West Family Memorial Fund, the Timeposters Fellowship, the University Health Network Centre for Mental Health, and the University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. Kayla M. Teopiz has received personal fees from Braxia Scientific Corp. Joshua D. Di Vincenzo is a consultant to Braxia Scientific Corp. David C.J. Chen-Li is a consultant to Braxia Scientific Corp.

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Jawad, M.Y., Alnefeesi, Y., Ceban, F. et al. Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review. Curr Psychiatry Rep 24, 359–368 (2022). https://doi.org/10.1007/s11920-022-01344-1

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