lumateperone

Antipsychotic

Brands: CAPLYTA

Last reviewed 2025-12-29

Reviewed by PsychMed Editorial Team.

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Quick answers

What is lumateperone?
Lumateperone (Caplyta; lumateperone tosylate) is a serotonin–dopamine activity modulator approved for adults with schizophrenia, depressive episodes associated with bipolar I or II disorder, and adjunctive treatment of major depressive disorder.
What is CAPLYTA?
CAPLYTA is a brand name for lumateperone.
What is CAPLYTA (lumateperone) used for?
Label indications include: Schizophrenia; depressive episodes associated with bipolar I or II disorder; adjunctive treatment of major depressive disorder.
What drug class is CAPLYTA (lumateperone)?
Antipsychotic.
What is the mechanism of action of CAPLYTA (lumateperone)?
5‑HT2A antagonism; D2 presynaptic partial agonist and postsynaptic antagonist; SERT inhibition.
What strengths does CAPLYTA (lumateperone) come in?
Oral capsules 10.5 mg, 21 mg, 42 mg (therapeutic target 42 mg once daily with or without food).
Is CAPLYTA (lumateperone) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.
What is CAPLYTA (lumateperone) dosing for schizophrenia?
Schizophrenia, bipolar depression, and adjunctive major depressive disorder: 42 mg orally once daily with or without food; no titration required.
What is the maximum recommended dose of CAPLYTA (lumateperone)?
Maximum recommended dose: 42 mg once daily.
What is the maximum dose of CAPLYTA (lumateperone) for major depressive disorder (clinical depression)?
Schizophrenia, bipolar depression, and adjunctive major depressive disorder: 42 mg orally once daily with or without food; no titration required.

Snapshot

Class: Antipsychotic
Common US brands: CAPLYTA
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-29

Label indications

Schizophrenia; depressive episodes associated with bipolar I or II disorder; adjunctive treatment of major depressive disorder.

View labelExact

Clinical Highlights

Lumateperone (Caplyta; lumateperone tosylate) is a serotonin–dopamine activity modulator approved for adults with schizophrenia, depressive episodes associated with bipolar I or II disorder, and adjunctive treatment of major depressive disorder. Lumateperone mechanism of action pairs 5-HT2A antagonism with presynaptic D2 partial agonism, postsynaptic D2 antagonism, and serotonin reuptake inhibition, yielding antipsychotic and antidepressant effects with comparatively low EPS and metabolic impact.

It is dispensed as a fixed 42 mg once-daily capsule without titration, offering placebo-like EPS rates and minimal metabolic change—useful when weight gain, prolactin elevation, or EPS with other SGAs limit therapy.
Because it lacks antimanic efficacy, maintain concurrent mood stabilizers or antipsychotics that cover mania/hypomania when relapse prevention is needed.
The compare tool and lumateperone evidence feed can help contextualize sedation, metabolic impacts, and dosing logistics alongside alternative therapies; share bipolar education via the bipolar disorder hub.
Adoption is rising for patients needing a low-metabolic-burden option without titration. Insurance coverage, somnolence, and CYP3A4 interaction constraints remain practical barriers; screen medication lists are typically reviewed for interactions before initiation.
Schizophrenia (adults) (FDA 2019)
Bipolar I or II depressive episodes (adults, monotherapy or adjunct) (FDA 2021)
Adjunctive major depressive disorder (adults) (FDA 2025)

Dosing & Formulations

Oral capsules 10.5 mg, 21 mg, 42 mg (therapeutic target 42 mg once daily with or without food). Schizophrenia, bipolar depression, and adjunctive major depressive disorder: 42 mg orally once daily with or without food; no titration required.

Maximum recommended dose: 42 mg once daily.
Reduce to 21 mg once daily when co-administered with moderate CYP3A4 inhibitors (e.g., fluconazole, diltiazem); avoid strong CYP3A4 inhibitors or inducers.
Limit to 21 mg/day in moderate hepatic impairment; contraindicated in severe hepatic impairment. Severe renal impairment (CrCl <30 mL/min) is commonly approached cautiously.
Missed dose: if remembered within 12 hours, it is typically taken then; otherwise skipped and resumed at the next scheduled dose (doubling is avoided).

Monitoring & Risks

Boxed warning: Increased mortality in elderly patients with dementia-related psychosis (class warning). Boxed warning: Suicidal thoughts and behaviors in children, adolescents, and young adults treated with antidepressants; closer monitoring for worsening is common.

Somnolence/sedation: ≈17%; evening dosing or review of concurrent sedatives is often considered.
Dizziness: ≈10%; fall-prone patients may need closer monitoring.
Nausea: ≈10%; usually mild and transient.
Dry mouth: ≈10%; hydration and oral hygiene counseling is common.

Drug Interactions

Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole) markedly increase exposure and are contraindicated. Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John’s wort) substantially reduce exposure and are contraindicated.

Moderate CYP3A4 inhibitors warrant dose reduction to 21 mg/day with close monitoring.
Grapefruit/grapefruit juice is typically avoided due to CYP3A4 inhibition potential.
Additive CNS depression occurs with alcohol, benzodiazepines, opioids, or other sedatives—driving and machinery precautions are commonly discussed.

Practice Notes

Fixed once-daily dosing can aid adherence; pharmacy coverage and prior authorization are often reviewed early. Routine metabolic labs and blood pressure monitoring are typically continued despite favorable averages to maintain SGA safety standards.

Sedation, cognition, and fall risk are often reassessed within the first few weeks; evening dosing can minimize daytime somnolence.
Complementary antimanic therapy (e.g., lithium, valproate, or another SGA) is typically maintained or added when lumateperone is used for bipolar depression, since it does not prevent manic relapse.
Education for patients/caregivers often covers hypersensitivity symptoms (swelling, difficulty breathing) that warrant emergency care.
New prescriptions and over-the-counter products are typically reviewed with the prescribing team due to CYP3A4 sensitivity.

References

CAPLYTA (lumateperone) prescribing information — DailyMed (2025)
Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial — JAMA Psychiatry (2020)
Lumateperone FOR THE Treatment OF Bipolar Depression: Results From A Randomized, Double Blind, Placebo Controlled Trial — The Journal of Clinical Psychiatry (2021)
Lumateperone AS Adjunctive Therapy IN Patients With Major Depressive Disorder: Results From A Randomized, Double Blind, Phase 3 Trial. — Journal of Clinical Psychiatry (2025)
Adjunctive Lumateperone IN Patients With Major Depressive Disorder: Results From A Randomized, Double Blind, Phase 3 Trial. — American Journal of Psychiatry (2025)
The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)Guidelineschizophreniaclinical