Mechanism of Action: Lumateperone is unique among second-generation antipsychotics based on its target profile and dopamine D2 receptor occupancy. Unlike other antipsychotics, lumateperone has partial agonist activity at presynaptic dopamine (D2) receptors, resulting in reduced presynaptic release of dopamine, and antagonistic activity at postsynaptic dopamine (D2) receptors.
Lumateperone also targets dopamine (D1) receptors, and a useful secondary result of D1 activation is increased glutamatergic N-methyl-D-aspartate (NMDA) GluN2B receptor phosphorylation. This is significant since NMDA-mediated glutamate signaling appears to be impaired in patients who have schizophrenia.
Lumateperone is capable of modulating serotonin by inhibiting serotonin transporters (SERT), and by behaving as a 5-HT2A receptor antagonist.
Indications: BP-I, BP-II, schizophrenia
Interactions: There are 566 drugs known to interact with Caplyta (lumateperone), along with 9 disease interactions, and 4 alcohol/food interactions. Of the total drug interactions, 144 are major, 421 are moderate, and 1 is minor. -Drugs.com
Dosing Capsules: 42 mg, 21 mg, 10.5 mg. The typical dose is 42 mg by mouth once a day with food.
Quick Pearls
- What makes it special? First antipsychotic approved for schizophrenia and monotherapy for BP I and II. A great option for schizoaffective disorder.
- Pros: easy dosing (ONCE/day) and adjustments are not needed like with mood stabilizers, less metabolic effects compared to common SGAs; less likely to cause weight gain and movement disorders. No blood draw. Co-pay Savings Card is available for people who are eligible
- Cons: I’m not sure about using this for the initial manic episodes or in a crisis -there are no IV options. Rep recommended that this is for s/p hospitalization and maintenance. I’m still on the fence about the rapid cyclers or severe agitation (may take several weeks to lessen symptoms). Not approved for kids, nursing/pregnant risks. It needs to be taken with FOOD.
- Biggest S/E: sleepiness (take QHS) and nausea but self-limiting, it was recommended to prescribe Zofran for initial use and why it’s best to take with food. Interacts with several medications and supplements.
Additional Information
Official Medication Website: Caplyta (lumateperone)
- Information about Caplyta -Good RX
A New Option for Bipolar Depression –Psychiatric Times and Compared to Options:
Lumateperone for major depressive episodes in bipolar I or bipolar II disorder –MD Edge and Other Comparisons:
