The FDA has approved caplyta (lumateperone, from Intra-Cellular Therapies, Inc) for the treatment of schizophrenia in adults, which affects about 2.4 million Americans with a diverse presentation.1

Treatment is often stopped because of adverse effects (AEs), such as movement disorders and weight gain.2

Caplyta is an atypical antipsychotic and is thought to exert its effect through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors. Caplyta reaches steady-state plasma concentrations after about 5 days and has a terminal elimination half-life of about 18 hours.1

The recommended dose of Caplyta is 42 mg once daily with food. It does not require dose titration.1

The role of Caplyta in schizophrenia was studied in 2 placebo-controlled trials. Study 1 was a double-blind, multicenter, placebo-controlled, randomized, 4-week study of 335 adults with a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria. Participants were randomized to receive Caplyta 42 mg, Caplyta 84 mg, an active comparator, or a placebo. Because of the study’s design, comparison of efficacy between Caplyta and the active comparator was not possible. At the end, participants who received Caplyta 42 mg displayed a statistically significant reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared with those who received a placebo. No statistically significant difference was found between those taking Caplyta 84 mg and a placebo.

Study 2 was a double-blind, multicenter, placebo- controlled, randomized, 4-week study of 450 adults with a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. Participants were randomized to receive Caplyta 28 mg, Caplyta 42 mg, or a placebo. Compared with the placebo group, patients using Caplyta 42 mg showed a statistically significant reduction in the PANSS total score. There was no statistically significant difference between the participants using Caplyta 28 mg and a placebo.1

Pooled data from short-term studies showed that the mean changes from baseline in fasting glucose, total cholesterol, triglycerides, and weight gain were similar between patients using Caplyta or a placebo.

Caplyta carries a boxed warning stating that elderly patients with dementia-related psychosis who are treated with antipsychotic medications are at an increased risk of death, so should not be used for these patients.

Caplyta is contraindicated in patients with a hypersensitivity to the medication or any of its components.

Elderly patients with dementia who are treated with certain antipsychotic agents may have an increased incidence of cerebrovascular AEs, including fatal stroke. If neuroleptic malignant syndrome is suspected, Caplyta should be discontinued immediately, and intensive symptomatic treatment and monitoring should be provided. Discontinuation of treatment may be warranted if signs and symptoms of tardive dyskinesia occur. Patients using Caplyta should be monitored for diabetes mellitus, dyslipidemia, hyperglycemia, and weight gain. Leukopenia and neutropenia have been reported during treatment with antipsychotic agents, including Caplyta. Agranulocytosis, including fatal cases, has been reported with other antipsychotic agents. Patients with a history of leukopenia, neutropenia, or a pre-existing low white blood cell count should have a complete blood count checked frequently during the first few months of treatment. Consider discontinuation of Caplyta if a clinically significant decline in white blood cell count occurs without other causative factors. Because atypical antipsychotics can cause orthostatic hypotension and syncope, patients with known cardiovascular or cerebrovascular disease and those at risk for dehydration or syncope should have their blood pressure and heart rates monitored.

Caplyta should be used cautiously in patients with a history of seizures or conditions that lower the seizure threshold. Caplyta should not be used with cytochrome P450 3A4 inducers or moderate or strong cytochrome P450 3A4 inhibitors or in those with moderate or severe hepatic impairment. When used in the third trimester of pregnancy, Caplyta may cause extrapyramidal and/ or withdrawal symptoms in neonates. It should not be used in women who are breastfeeding.

The most common AEs were dry mouth, sedation, and somnolence.1
Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Health Care System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

  1. Caplyta.Prescribing information. Intra-Cellular Therapies, Inc; 2019. Accessed February 25, 2020.
  2. FDA approves Intra-Cellular Therapies’ novel antipsychotic, Caplyta (lumateperone) for the treatment of schizophrenia in adults.Newsrelease. Intra-Cellular Therapies, Inc; December 23, 2019. Accessed February 25,