What is the appropriate dosing, contraindications, monitoring, and side‑effect considerations for Caplyta (lumateperone) in an adult with schizophrenia or bipolar I depression?

Caplyta (Lumateperone) for Schizophrenia and Bipolar Depression

Dosing

The recommended dosage of Caplyta is 42 mg once daily, taken with or without food, and dose titration is not required. 1

Standard Dosing

• Schizophrenia and bipolar depression: 42 mg once daily 1
• No titration needed—start at full therapeutic dose 1
• Can be taken with or without food 1

Dose Adjustments for Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Reduce to 10.5 mg once daily 1
• Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin): Reduce to 21 mg once daily 1
• CYP3A4 inducers (e.g., carbamazepine, rifampin): Avoid concomitant use entirely 1

Hepatic Impairment

• Moderate or severe hepatic impairment: Reduce to 21 mg once daily 1
• Mild hepatic impairment: No adjustment needed 1

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Contraindications

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

Absolute Contraindications

• Known hypersensitivity to lumateperone 1
• Concomitant use with CYP3A4 inducers 1, 2

Populations Where Use Is Not Recommended

• Elderly patients with dementia-related psychosis: Increased risk of death 1
• Pregnant or breastfeeding women: May cause extrapyramidal and/or withdrawal symptoms in neonates with third-trimester exposure 1, 2
• Children and adolescents: Safety and effectiveness not established in pediatric patients 1
• Patients at risk for cerebrovascular disease: Increased incidence of stroke and transient ischemic attacks 1, 2
• Patients using alcohol or other sedating agents: Additive sedation risk 2

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Monitoring Requirements

Baseline Assessment

Before initiating Caplyta, obtain:

• Metabolic parameters: Body mass index (BMI), waist circumference, blood pressure, fasting glucose, HbA1c, and fasting lipid panel 3
• Complete blood count (CBC): Especially in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia 1
• Cardiovascular assessment: Heart rate and blood pressure, particularly in patients with known cardiovascular or cerebrovascular disease 1
• Movement disorder screening: Document any preexisting abnormal movements to avoid later mislabeling them as medication-induced side effects 4

Ongoing Monitoring

• Metabolic parameters: Monitor BMI monthly for 3 months, then quarterly; reassess blood pressure, fasting glucose, and lipids at 3 months, then annually 5
• CBC: Perform complete blood counts in patients with pre-existing low WBC or history of leukopenia or neutropenia; consider discontinuing Caplyta if clinically significant decline in WBC occurs without other causative factors 1
• Orthostatic vital signs: Monitor heart rate and blood pressure regularly, especially during dose initiation and in patients at risk for dehydration or syncope 1
• Movement disorders: Assess for tardive dyskinesia at each visit; discontinue treatment if clinically appropriate 1
• Mood and suicidality: Closely monitor all patients for worsening depression and emergence of suicidal thoughts and behaviors, particularly during the first few months of treatment 1

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Side Effects and Safety Considerations

Most Common Adverse Reactions (>5% and twice placebo rate)

• Schizophrenia: Somnolence/sedation and dry mouth 1
• Bipolar depression: Somnolence/sedation, dizziness, nausea, and dry mouth 1

Serious Adverse Reactions

Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation and close monitoring for hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability. 1

Tardive Dyskinesia: Risk increases with duration of treatment and total cumulative dose; discontinue Caplyta if clinically appropriate. 1

Metabolic Changes:

• Hyperglycemia/diabetes mellitus: Monitor fasting glucose and HbA1c at baseline, 3 months, then annually 1
• Dyslipidemia: Monitor fasting lipid panel at baseline, 3 months, then annually 1
• Weight gain: Monitor BMI monthly for 3 months, then quarterly 1

Leukopenia, Neutropenia, and Agranulocytosis: Perform CBC in patients with pre-existing low WBC or history of leukopenia or neutropenia; consider discontinuing if clinically significant decline in WBC occurs. 1

Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure; warn patients with known cardiovascular or cerebrovascular disease and those at risk for dehydration or syncope. 1

Seizures: Use cautiously in patients with a history of seizures or conditions that lower seizure threshold. 1

Cognitive and Motor Impairment: Advise patients to use caution when operating machinery or driving until they know how Caplyta affects them. 1

Favorable Safety Profile

• Low extrapyramidal symptoms (EPS): Lumateperone shows relatively low rates of EPS compared to traditional neuroleptics due to less than 50% dopamine D2 receptor occupancy 3, 6
• Minimal metabolic disturbances: Compared to other atypical antipsychotics, lumateperone has a favorable metabolic profile with minimal weight gain and metabolic dysfunction 2, 7
• No endocrine dysregulation: Unlike many antipsychotics, lumateperone does not cause significant prolactin elevation 7

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Clinical Considerations

Unique Pharmacology

Lumateperone is a first-in-class agent that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, providing efficacy across a wide range of symptoms including social function and depression. 7, 8

Indications

• Schizophrenia in adults 1
• Depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate 1

Special Populations

• Bipolar II depression: Lumateperone is the only agent approved as an adjunct to mood stabilizers for bipolar II depression 6
• Treatment-resistant schizophrenia: Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for those vulnerable to developing metabolic dysfunction and movement disorders 2

Common Pitfalls to Avoid

• Do not combine with CYP3A4 inducers: This reduces lumateperone levels below therapeutic range 1, 2
• Do not use in elderly patients with dementia-related psychosis: Increased mortality risk 1
• Do not use in pregnant or breastfeeding women without careful risk-benefit assessment: Risk of neonatal extrapyramidal and withdrawal symptoms 1, 2
• Do not combine with alcohol or other sedating agents: Additive sedation risk 2
• Do not assume efficacy for all phases of bipolar disorder: Long-term maintenance data remain limited 3