Introduction
Caplyta (lumateperone) is an atypical antipsychotic medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia in adults and for depressive episodes associated with bipolar I or bipolar II disorder in adults. Developed by Intra-Cellular Therapies, Caplyta represents a novel therapeutic option with a unique receptor binding profile that distinguishes it from other antipsychotic medications.
Mechanism of Action
Lumateperone's mechanism of action is complex and multifactorial. It functions as a serotonin 5-HT2A receptor antagonist, dopamine D2 receptor antagonist, and serotonin reuptake inhibitor. Additionally, it demonstrates partial agonist activity at serotonin 5-HT1A receptors and modulates glutamatergic neurotransmission through indirect effects on NMDA and AMPA receptors. This unique combination of pharmacological activities is thought to contribute to its efficacy in both schizophrenia and bipolar depression while potentially offering a favorable side effect profile compared to traditional antipsychotics.
Indications
- Treatment of schizophrenia in adults
- Monotherapy or adjunctive therapy for depressive episodes associated with bipolar I or bipolar II disorder in adults
Dosage and Administration
Standard dosing: 42 mg once daily with food Administration: Oral capsule formulation Special populations:- Hepatic impairment: No dosage adjustment required
- Renal impairment: No dosage adjustment required
- Elderly patients: No dosage adjustment required
- CYP3A4 inhibitors: Reduce dosage to 21 mg once daily
- CYP3A4 inducers: Avoid concomitant use
Pharmacokinetics
Absorption: Peak plasma concentrations achieved within 2-4 hours post-dose Distribution: Extensive tissue distribution with volume of distribution >1000 L Metabolism: Primarily metabolized by CYP3A4 and UGT1A4 enzymes Elimination: Terminal half-life approximately 18 hours; primarily excreted in feces (58%) and urine (29%)Contraindications
- Hypersensitivity to lumateperone or any component of the formulation
- Concomitant use with strong CYP3A4 inducers
Warnings and Precautions
- Increased mortality in elderly patients with dementia-related psychosis: Antipsychotics have shown increased risk of death in this population
- Suicidal thoughts and behaviors: Monitor for emergence or worsening of depression
- Neuroleptic malignant syndrome: Monitor for hyperpyrexia, muscle rigidity, altered mental status
- Tardive dyskinesia: May develop with chronic use
- Metabolic changes: Monitor for weight gain, hyperglycemia, dyslipidemia
- Leukopenia/neutropenia: Has been reported with antipsychotic use
- Orthostatic hypotension and syncope: May occur, particularly during initial titration
- Seizures: Use with caution in patients with history of seizures
- Cognitive and motor impairment: May impair judgment, thinking, or motor skills
Drug Interactions
- Strong CYP3A4 inhibitors: Increase lumateperone exposure (reduce dose to 21 mg)
- Strong CYP3A4 inducers: Decrease lumateperone exposure (avoid concomitant use)
- CNS depressants: May potentiate sedative effects
- Antihypertensive agents: May enhance hypotensive effects
Adverse Effects
Common adverse reactions (≥5%):- Somnolence/sedation
- Dry mouth
- Nausea
- Dizziness
- Fatigue
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Metabolic syndrome
- Leukopenia/neutropenia
- Orthostatic hypotension
- Seizures
- Suicidal ideation
Monitoring Parameters
- Baseline and periodic:
- Complete blood count - Metabolic panel (glucose, lipids) - Weight and BMI - Blood pressure (sitting and standing)
- Clinical monitoring:
- Mental status examination - Extrapyramidal symptoms assessment - Suicidal ideation assessment - Treatment response evaluation
Patient Education
- Take medication exactly as prescribed, with food
- Avoid alcohol consumption during treatment
- Do not drive or operate machinery until effects are known
- Report any unusual movements, fever, muscle rigidity, or changes in mental status
- Monitor for weight changes and report significant gain
- Inform all healthcare providers about Caplyta use
- Do not stop medication abruptly without medical supervision
- Use effective contraception during treatment
- Report any thoughts of self-harm or worsening depression
References
1. FDA Prescribing Information: Caplyta (lumateperone). 2023 2. Correll CU, et al. Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2020;77(4):349-358 3. Calabrese JR, et al. Efficacy and Safety of Lumateperone in Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial. Am J Psychiatry. 2021;178(12):1098-1106 4. Snyder GL, et al. The neuropharmacology of lumateperone: a novel therapeutic agent for the treatment of schizophrenia. CNS Spectr. 2021;26(3):227-235 5. Vanover KE, et al. Dopamine D2 receptor occupancy of lumateperone (ITI-007): a positron emission tomography study in patients with schizophrenia. Neuropsychopharmacology. 2019;44(3):598-605
This monograph is intended for educational purposes only and should not replace professional medical advice. Healthcare providers should consult the full prescribing information before initiating therapy.