Lumateperone (Caplyta)

Class

Atypical antipsychotic with multimodal activity

Mechanism

Potent antagonism at serotonin 5-HT₂A receptors, presynaptic partial agonism and postsynaptic antagonism at dopamine D₂ receptors, and indirect modulation of glutamatergic neurotransmission via dopamine D₁ receptor-dependent mechanisms. This multi-receptor activity is thought to underlie its antipsychotic, antidepressant, and procognitive effects, distinguishing it from other second-generation antipsychotic agents.

FDA-Approved Use

Schizophrenia; depressive episodes associated with bipolar I or II disorder (monotherapy and adjunctive to lithium or valproate)

Off-Label Use

Limited off-label use due to novel status; potential utility in neuropsychiatric symptom management

Formulation

Oral capsules

Titration

42 mg p.o. once daily with food; no titration required

Dose Range

42 mg daily

Kinetics

Oral bioavailability improved with food; metabolized primarily via CYP3A4 and CYP1A2; half-life approximately 18 hours

Common AEs

Somnolence, dry mouth, dizziness, nausea

Serious/Rare AEs

Low risk of weight gain, extrapyramidal symptoms, or metabolic abnormalities reported

Monitoring

Monitor for sedation, metabolic parameters, and extrapyramidal symptoms as clinically indicated

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis

Considerations

Lumateperone may be preferred in patients with dementia, Parkinson’s disease (PD), or traumatic brain injury (TBI) due to its low sedation, metabolic, and extrapyramidal symptom risks. Its once-daily dosing can improve adherence in neuropsychiatric populations.