Caplyta (Lumateperone) Indications
Caplyta is FDA-approved for two specific indications in adults: schizophrenia and 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 received FDA approval in December 2019 for the treatment of schizophrenia in adults at a fixed dose of 42 mg once daily. 1, 2
- No dose titration is required for this indication. 1
- The approval was based on two positive, well-controlled randomized trials demonstrating efficacy across positive symptoms, with additional benefits observed in social function and depressive symptoms. 3, 4
Bipolar Depression in Adults
- Caplyta is indicated for depressive episodes associated with bipolar I or II disorder in adults. 1
- It can be used as monotherapy or as adjunctive therapy with lithium or valproate. 1
- The recommended dosage remains 42 mg once daily for this indication. 1
Classification
- Lumateperone is classified as a third-generation antipsychotic alongside aripiprazole, cariprazine, and brexpiprazole, distinguishing it from second-generation and first-generation antipsychotics. 5, 6
Critical Contraindications and Black Box Warnings
Absolute Contraindications
- NOT approved for elderly patients with dementia-related psychosis due to increased mortality risk (1.6 to 1.7 times higher than placebo). 1
- Contraindicated in patients with history of hypersensitivity reactions including pruritus, rash, or urticaria. 1
- NOT approved for pediatric patients (safety and effectiveness not established). 1
Black Box Warning for Suicidal Thoughts
- Carries a black box warning for increased risk of suicidal thoughts and behaviors in pediatric and young adult patients (under 24 years) treated with antidepressants. 1
- Close monitoring is required for clinical worsening and emergence of suicidal ideation, particularly during initial treatment months. 1
Dosing Adjustments Required
Drug Interactions
- Strong CYP3A4 inhibitors: Reduce dose to 10.5 mg once daily. 1
- Moderate CYP3A4 inhibitors: Reduce dose to 21 mg once daily. 1
Hepatic Impairment
- Moderate or severe hepatic impairment (Child-Pugh class B or C): Reduce dose to 21 mg once daily. 1
Clinical Considerations
Potential Advantages
- Favorable safety profile with lower risk of extrapyramidal symptoms (EPS) and metabolic disturbances compared to many other antipsychotics. 7, 4
- Most common adverse effects are mild: headache, somnolence, dizziness, sedation, constipation, and fatigue. 4, 8
- May be particularly beneficial for patients with treatment-resistant schizophrenia or those vulnerable to metabolic dysfunction and movement disorders. 7
Important Cautions
- Should not be used in pregnant or breastfeeding women. 7
- Avoid in patients at risk for cerebrovascular diseases. 7
- Do not use with CYP3A4 inducers or in patients using alcohol and other sedating agents. 7
- Monitor for cerebrovascular adverse reactions including stroke, particularly in elderly patients. 1