What are the indications for Caplyta (lumateperone)?

Caplyta (Lumateperone) Indications

Caplyta is FDA-approved for two specific indications in adults: (1) schizophrenia, and (2) depressive episodes associated with bipolar I or II disorder (bipolar depression), either as monotherapy or as adjunctive therapy with lithium or valproate. 1

FDA-Approved Indications

Schizophrenia in Adults

• Lumateperone is indicated for the treatment of schizophrenia in adults at a fixed dose of 42 mg once daily, with no titration required 1
• The drug is classified as a third-generation antipsychotic alongside aripiprazole, cariprazine, and brexpiprazole 2
• Clinical trials demonstrated statistically significant reduction in Positive and Negative Syndrome Scale (PANSS) scores compared to placebo over 4-week periods 3

Bipolar Depression in Adults

• Lumateperone is approved for depressive episodes associated with bipolar I or II disorder in adults 1
• Can be used as monotherapy or as adjunctive therapy with lithium or valproate 1
• The same 42 mg once daily dosing applies, with no titration needed 1

Dosing Specifications

Standard Dosing

• The recommended dose is 42 mg administered orally once daily with or without food 1
• No dose titration is required, which simplifies initiation 1

Dose Adjustments Required

• Moderate CYP3A4 inhibitors: Reduce to 21 mg once daily 1
• Strong CYP3A4 inhibitors: Reduce to 10.5 mg once daily 1
• Moderate or severe hepatic impairment (Child-Pugh class B or C): Reduce to 21 mg once daily 1

Critical Contraindications and Black Box Warnings

Absolute Contraindications

• History of hypersensitivity reaction to lumateperone, including pruritus, rash (allergic dermatitis, papular rash, generalized rash), and urticaria 1

Black Box Warnings

• Increased mortality in elderly patients with dementia-related psychosis: Caplyta is NOT approved for dementia-related psychosis and carries a 1.6 to 1.7 times increased risk of death compared to placebo 1
• Suicidal thoughts and behaviors: Antidepressants, including lumateperone when used for bipolar depression, increase risk of suicidal ideation in pediatric and young adult patients (age <25 years) 1
• Close monitoring is required during initial months of therapy and at dosage changes 1

Additional High-Risk Populations to Avoid

• Pregnant or breastfeeding women 4
• Children and adolescents (safety and effectiveness not established in pediatric patients) 1
• Patients at risk for cerebrovascular diseases 4
• Patients using CYP3A4 inducers or moderate/strong inhibitors without dose adjustment 4
• Patients using alcohol and other sedating agents concurrently 4

Clinical Considerations

Potential Advantages

• Favorable safety profile with lower risk of extrapyramidal symptoms (EPS) compared to other antipsychotics 3
• Lower risk of metabolic disturbances (weight gain, metabolic syndrome) compared to many second-generation antipsychotics 4, 3
• May benefit patients with treatment-resistant schizophrenia 4
• Addresses multiple symptom domains including social function and depression through simultaneous modulation of serotonin, dopamine, and glutamate neurotransmission 5

Common Adverse Effects

• Most common treatment-emergent adverse events in clinical trials were headache, somnolence, and dizziness 3
• Additional reported effects include sedation, constipation, and fatigue 6
• These effects were generally mild at the 42 mg recommended dose 6

Important Monitoring

• Monitor for clinical worsening and emergence of suicidal thoughts, especially in young adults treated for bipolar depression 1
• Assess for cerebrovascular adverse reactions in elderly patients, though use in dementia-related psychosis is contraindicated 1