Lumateperone ($ Caplyta)
Second generation antipsychotic (dopamine D2 angaonist with low occupancy (40%); antagonist at serotonin 5-HT2A receptors; inhibits serotonin areuptake)
- Bipolar I & II Depression [1]
- Schizophrenia [1]
- Bipolar Mania and Mixed [1]
- Treatment resistant depression [2]
Features
Dosing
Start 10.5-21 mg qhs, raise every 3-5 days to 42mg/d. Same dose in mood disorders and schizophrenia.
INTERACTIONS: Metabolized by 3A4. Raise 3-5x with carbamazepine. Lower 2x with nefazodone and grapefruit juice. May need to lower a little with non-pram SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline ≥ 150 mg/day).
Management
Main SE is sedation. Low risk of weight gain, akathisia, prolactin or metabolic problems. Although it has efficacy in acute bipolar depression and mania, it has no known ability to prevent future episodes.
TOLERABILITY: Weight gain, sedation, akathisia, EPS (dystonia, stiffness), anticholinergic.
RISKS: Tardive dyskinesia (25% over 10 years, higher in elderly), metabolic, prolactinemia (can lead to breast cancer, osteopenia, sexual dysfunction), orthostasis (falls), QTc prolongation, temperature imbalance in elderly, NMS (muscle rigidity, fever, tachycardia).
EMR Text
Bipolar depression
Lumateperone use based on FDA approval in bipolar depression.
Antipsychotic side effects, including metabolic and TD, reviewed with patient.
Bipolar mania
Lumateperone use based on a large, randomized trial in bipolar mania (Cutler AJ et al, poster presented at Psych Congress 2026).
Antipsychotic side effects, including metabolic and TD, reviewed with patient.
Schizophrenia
Lumateperone use based on FDA approval in schizophrenia.
Antipsychotic side effects, including metabolic and TD, reviewed with patient.