What is the indication for Caplyta (lumateperone) in adults with schizophrenia?

Caplyta (Lumateperone) Indications

Caplyta is FDA-approved for two specific indications in adults: (1) treatment of schizophrenia, and (2) treatment of 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

• Caplyta is indicated for the treatment of schizophrenia in adults at a recommended dosage of 42 mg once daily. 1
• No dose titration is required, and it can be taken with or without food. 1
• The approval was based on two positive, well-controlled clinical trials demonstrating efficacy across a wide range of schizophrenia symptoms, including positive symptoms, social function, and depression. 2

Bipolar Depression in Adults

• Caplyta is indicated for depressive episodes associated with bipolar I or II disorder in adults, both as monotherapy and as adjunctive therapy with lithium or valproate. 1
• The same dosing regimen applies: 42 mg once daily without need for titration. 1

Dosing Modifications

Hepatic Impairment

• For patients with moderate or severe hepatic impairment, the recommended dosage is reduced to 21 mg once daily. 1

Drug Interactions

• When co-administered with strong CYP3A4 inhibitors, reduce the dose to 10.5 mg once daily. 1
• When co-administered with moderate CYP3A4 inhibitors, reduce the dose to 21 mg once daily. 1
• Avoid concomitant use with CYP3A4 inducers. 1

Critical Safety Considerations

Boxed Warnings

• Caplyta carries two boxed warnings: (1) increased mortality in elderly patients with dementia-related psychosis, and (2) suicidal thoughts and behaviors in pediatric and young adult patients treated with antidepressants. 1
• Caplyta is NOT approved for treatment of dementia-related psychosis. 1
• Safety and effectiveness have NOT been established in pediatric patients. 1

Contraindications

• Caplyta is contraindicated in patients with known hypersensitivity to lumateperone or any components of the medication. 1

Clinical Profile and Positioning

Unique Pharmacology

• Lumateperone simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, distinguishing it as a first-in-class agent. 2, 3
• It demonstrates higher affinity for serotonin (5-HT2A) receptors compared with dopamine (D2) receptors, but with lower affinities for α-1 and histaminergic receptors than other second-generation antipsychotics. 4

Efficacy Evidence

• In pooled analysis of informative studies, lumateperone 42 mg/day showed statistically significant number needed to treat (NNT) versus placebo of 8-9 for ≥20-30% improvement on PANSS total scores at 4 weeks. 5
• The benefit-risk assessment was favorable, with likelihood to be helped or harmed (LHH) ratios ranging from 13.6 to 48.6 for most adverse events. 5

Safety Profile

• The most common adverse reactions (incidence >5% and greater than twice placebo) in schizophrenia trials were somnolence/sedation and dry mouth. 1
• In bipolar depression trials, the most common adverse reactions were somnolence/sedation, dizziness, nausea, and dry mouth. 1
• Discontinuation due to adverse events was uncommon, with a number needed to harm (NNH) of 389 (not statistically significant from placebo). 5
• Lumateperone was not significantly associated with extrapyramidal symptoms or metabolic adverse effects commonly seen with other antipsychotics. 4
• Rates of akathisia were actually lower for lumateperone compared with placebo. 5

Clinical Positioning

• Lumateperone merits particular consideration for patients with treatment-resistant schizophrenia and for patients vulnerable to developing metabolic dysfunction and movement disorders. 6
• The favorable metabolic and extrapyramidal symptom profile makes it an attractive option for patients intolerant to these effects with other antipsychotics. 4

Populations Where Caplyta Should NOT Be Used

Caplyta should be avoided in the following populations: 6

• Women who are pregnant or breastfeeding (may cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure) 1
• Children and adolescents (safety and effectiveness not established) 1
• Elderly patients with dementia-related psychosis (increased mortality risk) 1
• Patients at risk for cerebrovascular diseases 6
• Patients using CYP3A4 inducers or moderate/strong inhibitors without dose adjustment 1, 6
• Patients using alcohol and other sedating agents 6