Background
Bipolar disorder is a chronic disorder characterized by a significant disease burden. While many agents effectively treat symptoms of mania, treatments for depressive episodes associated with bipolar disorder are limited. Lumateperone, a mechanistically novel antipsychotic, is Food and Drug Administration (FDA) approved for the treatment of schizophrenia and depressive episodes associated with bipolar I and bipolar II disorder as monotherapy or as adjunctive therapy with lithium or valproate. This Phase 3, randomized, double-blind, placebo-controlled study assessed the safety and efficacy of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression.
Methods
- Patients (18-75 years) with bipolar I or bipolar II disorder undergoing a major depressive episode (MDE), with ineffective therapeutic response to lithium or valproate, were randomized to 1:1:1 to 6 weeks adjunctive therapy with lumateperone 28 mg (n=176), lumateperone 42 mg (n=177), or placebo (n=176).
- The primary and secondary efficacy endpoints were changed from the baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score and the Clinical Global Impression Scale-Bipolar Version-Severity Scale (CGI-BP-S) depression subscore.
- Safety examinations included adverse events, vital signs, laboratory evaluations, extrapyramidal symptoms, and suicidality.
Results
- Patients treated with adjunctive lumateperone 42 mg indicated significantly greater improvement compared with adjunctive placebo in MADRS total score and CGI-BP-S depression subscore.
- Adjunctive lumateperone 28 mg indicated numerical improvement in MADRA total score and improvement in the CGI-BP-S depression subscore.
- Adjunctive lumateperone treatment was well-tolerated.
- Treatment-emergent adverse events were reported at rates >5% and twice the placebo for lumateperone 42 mg were dizziness, somnolence, and nausea with limited risk of metabolic abnormalities or increased prolactin.
Conclusion
Lumateperone 42 mg treatment adjunctive to lithium and valproate significantly improved depression symptoms and was commonly well tolerated in patients with major depressive episodes associated with either bipolar I or bipolar II disorder.