Lumateperone

The mechanism of action of lumateperone for the treatment of schizophrenia in adults, for the treatment of depressive episodes associated with bipolar depression (as monotherapy or as adjunctive therapy with lithium or valproate), and as adjunctive therapy with antidepressants for the treatment of MDD is unknown. However, the mechanism of action of lumateperone for these uses could be mediated through a combination of antagonist activity at central serotonin 5-HT 2A receptors, and partial agonist activity at central dopamine D 2 receptors.

• CAPLYTA is indicated for: Treatment of schizophrenia in adults [see Clinical Studies (14.1) ] . Treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate [see Clinical Studies (14.2) ] .ICD-10: F20.9

• CAPLYTA is contraindicated in patients with history of hypersensitivity reaction to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g.contraindicated

Recommended oral dosage of CAPLYTA is 42 mg once daily with or without food. ( 2.1 ) Moderate hepatic impairment or severe hepatic impairment: Recommended dosage is 21 mg once daily. ( 2.3 , 8.6 ) 2.1 Recommended Dosage The recommended CAPLYTA dosage is 42 mg administered orally once daily with or without food. Dose titration is not needed. 2.2 Dosage Recommendations for Concomitant Use with Moderate or Strong CYP3A4 Inhibitors The recommended CAPLYTA dosage in patients who receive [see Drug Interactions ( 7.1 ) ] : Strong CYP3A4 inhibitors is 10.5 mg once daily. Moderate CYP3A4 inhibitors is 21 mg once daily. 2.3 Dosage Recommendations for Patients with Hepatic Impairment For patients with moderate hepatic impairment (HI) (Child-Pugh class B) or severe HI (Child-Pugh class C), the recommended CAPLYTA dosage is 21 mg once daily [see Use in Specific Populations (8.6) ] . The recommended CAPLYTA dosage in patients with mild HI is the same as those with normal hepatic function.

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke and transient ischemic attack). ( 5.3 ) Neuroleptic Malignant Syndrome: If NMS is suspected, immediately discontinue CAPLYTA and provide intensive symptomatic treatment and monitoring. ( 5.4 ) Tardive Dyskinesia: If signs and symptoms of TD occur consider discontinuing CAPLYTA treatment. ( 5.5 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.6 ) Leukopenia, Neutropenia, and Agranulocytosis : In patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia, perform complete blood counts (CBC). Consider discontinuing CAPLYTA if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue CAPLYTA in patients with clinically significant neutropenia or ANC < 1000/mm 3 and monitor closely until the neutropenia resolve. ( 5.7 ) Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure in patients who are vulnerable to hypotension. ( 5.8 ) Seizures: Use cautiously in patients with a history of seizures or with other conditions that lower seizure threshold. ( 5.10 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery and driving a motor vehicle until patients are reasonably certain that therapy with CAPLYTA does not affect them adversely.

The following adverse reactions are discussed in detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning , Warnings and Precautions (5.1) ] Suicidal Thoughts and Behaviors [see Boxed Warning , Warnings and Precautions (5.2) ] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-related Psychosis [see Warnings and Precautions (5.3) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.4) ] Tardive Dyskinesia [see Warnings and Precautions (5.5) ] Metabolic Changes [see Warnings and Precautions (5.6) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.7) ] Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.8) ] Falls [see Warnings and Precautions (5.9) ] Seizures [see Warnings and Precautions (5.10) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.11) ] Body Temperature Dysregulation [see Warnings and Precautions (5.12) ] Dysphagia [see Warnings and Precautions (5.13) ] Most common adverse reactions in clinical trials (incidence ≥ 5% and greater than twice placebo) were ( 6.1 ): Schizophrenia: somnolence/sedation and dry mouth. Bipolar depression: somnolence/sedation, dizziness, nausea, dry mouth. MDD: dizziness, dry mouth, somnolence/sedation, nausea, fatigue, diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Intra-Cellular Therapies, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including CAPLYTA, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ). Available data from case reports on CAPLYTA use in pregnant women are insufficient to establish any drug associated risks for birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including CAPLYTA, during pregnancy (see Clinical Considerations ). In animal reproduction studies, no malformations were observed with oral administration of lumateperone to pregnant rats and rabbits during organogenesis at doses up to 2.4 and 9.7 times, respectively, the maximum recommended human dose (MRHD) of 42 mg/day on a mg/m 2 basis.

Metabolism

Following once daily oral administration of CAPLYTA, lumateperone steady state is reached in about 5 days. Lumateperone steady-state exposure is approximately dose-proportional in the range of 3.5 mg to 56 mg (0.08 to 1.3 times the approved recommended daily dosage).

No specific antidotes for CAPLYTA are known. In managing a CAPLYTA overdose, provide supportive care, including close medical supervision and monitoring and consider the possibility of multiple drug involvement. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

• Dec 20, 2019NDANDA209500Intra-cellular

1. 1Dizziness66111%
2. 2Nausea4978.0%
3. 3Headache4497.2%
4. 4Somnolence3726.0%
5. 5Off Label Use3555.7%
6. 6Drug Ineffective2864.6%
7. 7Mania2544.1%
8. 8Feeling Abnormal2494.0%
9. 9Sedation2464.0%
10. 10Anxiety2403.9%
11. 11Insomnia2253.6%
12. 12Fatigue2213.6%
13. 13Vomiting2133.4%
14. 14Burning Sensation2033.3%
15. 15Suicidal Ideation1953.1%

The 10 most recently updated of 32 ClinicalTrials.gov registrations naming Lumateperone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Caplyta in Borderline Personality Disorder
  Completed · Phase 2 · Interventional · 60 enrolled · University of Chicago
  NCT05356013updated 2026-06-09
• Lumateperone for Late-Life Depression
  Not yet recruiting · Phase 3 · Interventional · 100 enrolled · Eric Lenze
  NCT07623135updated 2026-06-03
• Metabolic Effects of Adjunctive Lumateperone Treatment in Clozapine-Treated Patients With Schizophrenia
  Recruiting · Phase 4 · Interventional · 50 enrolled · University of Massachusetts, Worcester
  NCT06174116updated 2026-05-22
• Safety, Tolerability, and Pharmacokinetics of Lumateperone Long-Acting Injectable Formulations in Patients With Schizophrenia or Schizoaffective Disorder
  Completed · Phase 1 · Interventional · 52 enrolled · Intra-Cellular Therapies, Inc.
  NCT06627413updated 2026-03-12
• Neurocircuitry Mechanisms and Efficacy of Lumateperone as Adjunctive Therapy for Major Depressive Disorder and History of Early Life Abuse
  Not yet recruiting · Phase 4 · Interventional · 50 enrolled · University of Texas at Austin
  NCT07369115updated 2026-01-27
• Safety, Tolerability, and Pharmacokinetics of Lumateperone in Pediatric Patients With Schizophrenia or Schizoaffective Disorder
  Completed · Phase 1 · Interventional · 26 enrolled · Intra-Cellular Therapies, Inc.
  NCT04779177updated 2025-11-12
• An Open-label Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
  Completed · Phase 3 · Interventional · 812 enrolled · Intra-Cellular Therapies, Inc.
  NCT05061719updated 2025-11-03
• Clinical Trial Evaluating ITI-007 (Lumateperone) as a Monotherapy for the Treatment of Bipolar Depression
  Completed · Phase 3 · Interventional · 554 enrolled · Intra-Cellular Therapies, Inc.
  NCT02600494updated 2025-11-03
• Study of a Novel Antipsychotic ITI-007 in Schizophrenia
  Completed · Phase 2 · Interventional · 335 enrolled · Intra-Cellular Therapies, Inc.
  NCT01499563updated 2025-10-03
• A Trial to Assess the Antipsychotic Efficacy of ITI-007 Over 6 Weeks of Treatment
  Completed · Phase 3 · Interventional · 696 enrolled · Intra-Cellular Therapies, Inc.
  NCT02469155updated 2025-10-02

Frequently asked questions

How does Lumateperone work?

The mechanism of action of lumateperone for the treatment of schizophrenia in adults, for the treatment of depressive episodes associated with bipolar depression (as monotherapy or as adjunctive therapy with lithium or valproate), and as adjunctive therapy with antidepressants for the treatment of MDD is unknown. However, the mechanism of action of lumateperone for these uses could be mediated through a combination of antagonist activity at central serotonin 5-HT 2A receptors, and partial agonist activity at central dopamine D 2 receptors.

What is Lumateperone used for?

According to FDA labeling, Lumateperone carries indications including: CAPLYTA is indicated for: Treatment of schizophrenia in adults [see Clinical Studies (14.1) ] . Treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate [see Clinical Studies (14.2) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lumateperone?

Lumateperone is classified as Butyrophenone derivatives, Atypical Antipsychotic, Unknown Cellular or Molecular Interaction, Dopamine Activity Alteration, Serotonin Activity Alteration.

What are the brand names for Lumateperone?

Lumateperone is marketed under brand names including Caplyta.

What are the contraindications for Lumateperone?

Lumateperone labeling lists contraindications including: CAPLYTA is contraindicated in patients with history of hypersensitivity reaction to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g.. Always consult the full prescribing information and a clinician.