Caplyta as Adjunctive Therapy
Caplyta (lumateperone) is FDA-approved as adjunctive therapy with lithium or valproate for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults. 1
FDA-Approved Indications
Caplyta has three distinct FDA-approved uses 1:
- Schizophrenia in adults (as monotherapy)
- Bipolar depression in adults as monotherapy
- Bipolar depression in adults as adjunctive therapy with lithium or valproate 1
Evidence for Adjunctive Use
The adjunctive indication is based on a 6-week, randomized, double-blind, placebo-controlled trial (Study 4) in adult patients with bipolar I or II depression 1:
- 529 patients were randomized to receive Caplyta 42 mg, Caplyta 28 mg, or placebo, all in combination with lithium or valproate 1
- Caplyta 42 mg showed statistically significant improvement compared to placebo on the primary endpoint (MADRS total score change from baseline at Week 6), with a placebo-subtracted difference of -2.4 points (95% CI: -4.4, -0.4) 1
- The secondary endpoint (CGI-BP-S depression score) also showed statistically significant improvement with the 42 mg dose 1
- The 28 mg dose (two-thirds the recommended daily dose) did not achieve statistical significance, establishing 42 mg as the appropriate adjunctive dose 1
Clinical Context
Caplyta is NOT approved as adjunctive therapy for schizophrenia 1. While lumateperone is classified as a third-generation antipsychotic in systematic reviews 2, its adjunctive indication is specifically limited to bipolar depression when combined with mood stabilizers (lithium or valproate) 1.
The historical context from bipolar disorder guidelines indicates that antidepressants may be useful adjuncts for bipolar depression "as long as the patient is also taking at least one mood stabilizer" 2. Caplyta's approval as adjunctive therapy with lithium or valproate follows this established treatment paradigm for bipolar depression 1.