Lumateperone Shown to Significantly Improve Bipolar Depressive Symptoms

Treatment with lumateperone was found to significantly improve both depressive symptoms and severity of symptoms in patients with bipolar depression, with and without mixed features, according to the results of a study presented at Psych Congress 2021, held both virtually and in person from October 29 to November 1, 2021.

Patients diagnosed with bipolar disorder often experience symptoms of major depression — known as bipolar depression — either separately or concurrently with symptoms of mania.  To address this, investigators conducted a phase 3, randomized, double-blind, placebo-controlled study to assess the effect of treatment with lumateperone 42 mg on symptoms of bipolar depression. 

Lumateperone is a “mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission,” according to the investigators. Lumateperone was approved by the US Food and Drug Administration (FDA) in 2019 for schizophrenia treatment.

The 6-week bipolar disorder study involved patients aged 18 to 75 years with a diagnosis of bipolar I or II disorder who were experiencing a major depressive episode, as determined by the Montgomery-Åsberg Depression Rating Scale [MADRS] (total score ≥20), the Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] (score ≥4), and the Young Mania Rating Scale (score ≤12).

Primary and secondary endpoints included change from baseline to day 43 in MADRS Total and CGI-BP-S scores. Post hoc analyses examined patients with and without mixed features.

Of the 376 total patients treated, 41% exhibited mixed features. Compared with placebo, lumateperone was found to significantly improve MADRS total score for patients with mixed features (least square mean difference [LSMD], -4.4; 95% CI, -7.26 to -1.52; P =.0030) and without mixed features (LSMD, -4.2, 95% CI; -6.46 to -1.92; P =.0004) by day 43. Improvements in CGI-BP-S scores were similar in patients with mixed features (LSMD, -0.7; 95% CI, -1.43 to -0.05; P =.0369) and without mixed features (LSMD, -1.0; 95% CI, -1.62 to -0.47; P =.0004). The study revealed few instances of treatment-emergent mania or hypomania events (lumateperone, 3; placebo, 5).

Disclosure: This study was sponsored by Intra-Cellular Therapies, which also employed 6 of the 7 study authors.  Please refer to the original document for a full list of disclosures.

Reference

McIntyre R, Durgam S, Escher T, Huo J, Mates S, Stahl S. The efficacy of lumateperone in patients with bipolar depression with and without mixed features.  Poster presented at: Psych Congress 2021, October 29-November 1, 2021; San Antonio, Texas. Poster 39.