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Featured Clinical Article: Lumateperone for Treatment of Schizophrenia

06 Apr 2022 5:21 PM | Anonymous

Lumateperone for Treatment of Schizophrenia

By: Hae Shim, PharmD Candidate 2022, St. Louis College of Pharmacy

Mentor: Danielle Moses, PharmD, BCPP, SSM Health DePaul Hospital


Schizophrenia is a chronic psychological disorder that affects 1% of the general population1 and is considered one of the top 15 leading causes of disability worldwide.2 Schizophrenia is characterized by having two symptoms present for a significant portion of one month (less if treated). Symptoms may include delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms. At least one presenting symptom must be a positive symptom of schizophrenia- delusions, hallucinations, or disorganized speech.3 Although the progression of schizophrenia may differ among individuals, it can affect the quality of life if not managed properly.4

Treatment for schizophrenia requires pharmacological and psychosocial interventions. Pharmacological treatments include first-generation or second-generation antipsychotics. Second-generation antipsychotics are typically preferred due to the lower dopamine-mediated adverse effects.4 Current antipsychotic treatments are effective in reducing symptoms, but many medications are associated with adverse effects such as metabolic disturbances, cardiovascular risks, and hyperprolactinemia.1

Lumateperone (Caplyta)

On December 23, 2019, the Food and Drug Administration (FDA) approved lumateperone (Caplyta) for the treatment of schizophrenia.5 Lumateperone has shown to only need 40% striatal D2 receptor occupancy for treatment improvement in schizophrenia compared to other available antipsychotics that need 60-80% occupancy.1 The approved dose of lumateperone is 42 mg by mouth once daily with food. Although lumateperone is a once-daily administered oral medication due to its half-life of 13 to 21 hours, there are strict caloric requirements (at least 350 calories) during administration for its absorption.5

Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial

Lumateperone was  studied in a 4 week randomized, double-blinded, phase 3, placebo- controlled study conducted at 12 clinical sites from November 13, 2014, to July 20, 2015.1 Patients experiencing an acute exacerbation of psychosis were eligible to participate in the inpatient study, and were randomized in a 1:1:1 ratio to 42 mg lumateperone, 28 mg lumateperone, or placebo.1 All three groups were given once-daily oral administration in the morning. The study revealed significant improvement in symptoms of schizophrenia beginning at the first week and maintained throughout the 28 day treatment period.1 The study completion rates were 85.3% in the 42 mg lumateperone group, 80.0% in the 28 mg lumateperone group, and 74.0% in the placebo group.1 Overall, 20 participants in the 42 mg lumateperone group, 28 participants in the 28 mg lumateperone group, and 38 participants in the placebo group discontinued the study.1

Participants treated with 42 mg of lumateperone displayed a statistically significant improvement in the PANSS total score from baseline compared to placebo or treatment with lumateperone 28 mg (Table 1). Common adverse events observed were somnolence, sedation, fatigue, and constipation (Table 2). There was no increase in suicidal ideation or behavior as measured by Columbia Suicide Severity Rating Scale. No extrapyramidal symptoms related to treatment-emergent adverse events occurred in ≥ 5% of any treatment arm. There were no significant mean changes in metabolic parameters (cholesterol, glucose, triglycerides, prolactin, and insulin levels) from baseline to 28 days, and no QTc > 500 milliseconds or a change in QTc > 60 milliseconds from baseline.1


Lumateperone 42 mg demonstrated efficacy and safety for treatment of schizophrenia.1 Lumateperone may represent a preferred option for those who desire treatment with minimal cardiac, metabolic, and motor adverse events, though longer-term studies and head-to-head comparison trials are warranted to recommend its use over widely used agents with similar adverse effect profiles (e.g., aripiprazole).


  1. Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical Trial. JAMA Psychiatry. 2020;77(4):349-358.
  2. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390(10100):1211-1259.
  3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington D.C.: 2013.
  4. Keepers GA, Fochtmann LJ, Anzia JM, et al. The american psychiatric association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872.
  5. Lumateperone. In: Lexi-Drugs. Lexi-Comp, Inc. Updated September 30,2021. Accessed October 19, 2021.

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