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Randomized Controlled Trial
. 2023 Mar:68:78-88.
doi: 10.1016/j.euroneuro.2022.12.012. Epub 2023 Jan 13.

The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses

Roger S McIntyre  1 , Suresh Durgam  2 , Susan G Kozauer  2 , Richard Chen  2 , Jason Huo  2 , Robert E Davis  2 , Andrew J Cutler  3
Affiliations
Free article
Randomized Controlled Trial

The efficacy of lumateperone on symptoms of depression in bipolar I and bipolar II disorder: Secondary and post hoc analyses

Roger S McIntyre et al. Eur Neuropsychopharmacol. 2023 Mar.
Free article

Abstract

A recent Phase 3, randomized, double-blind, placebo-controlled study established that lumateperone 42-mg monotherapy significantly improved symptoms of depression in patients with bipolar depression. This manuscript reports prespecified secondary and post hoc efficacy analyses. Patients with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1 to lumateperone 42 mg or placebo, administered orally once daily for 6 weeks. Prespecified analyses evaluated change from baseline to Day 43 in individual Montgomery-Åsberg Depression Rating Scale (MADRS) item scores in the modified intent-to-treat population (mITT) and bipolar I and bipolar II disorder subgroups. Post hoc analyses investigated the MADRS anhedonia factor and categorical shifts in MADRS item scores. In the mITT, there was significant improvement from baseline to Day 43 with lumateperone 42 mg compared with placebo for all 10 MADRS items; most MADRS items significantly improved in subgroups with bipolar I (9 items) and bipolar II disorder (8 items). A significantly higher proportion of patients receiving lumateperone compared with placebo shifted from baseline MADRS item score ≥4 to ≤2 at end of treatment in Reported Sadness, Reduced Sleep, Concentration Difficulties, Lassitude, Inability to Feel, and Pessimistic Thoughts. Lumateperone significantly improved the MADRS anhedonia factor from baseline to Day 43 compared with placebo in the mITT (effect size, -0.47) and subgroups with bipolar I (-0.36) and bipolar II disorder (-0.90). Lumateperone 42 mg treatment significantly improved depression symptoms compared with placebo, with consistent efficacy across a broad range of symptoms in people with bipolar I and bipolar II disorder.

Keywords: Anhedonia; Antipsychotic agents; Bipolar I disorder; Bipolar II disorder; Bipolar depression; Lumateperone.

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Conflict of interest statement

Conflict of Interest R. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC); speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, Inc., NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences. R. McIntyre is a CEO of Braxia Scientific Corp. S. Durgam, S.G. Kozauer, R. Chen, and R.E. Davis are full-time employees of Intra-Cellular Therapies, Inc., and may hold company stock/stock options. A.J. Cutler has been a consultant for or received speaker/promotional honoraria from AbbVie/Allergan, Acadia Pharmaceuticals, Inc., AiCure, Alfasigma, Alkermes, Avanir Pharmaceuticals, Inc., Axsome Therapeutics Inc., BioXcel, Blackthorn, Boehringer Ingelheim, Cerevel, Corium, Gedeon Richter, Idorsia, Intra-Cellular Therapies, Inc., Janssen Pharmaceuticals, Inc., Karuna, Lundbeck, Luye Pharma, MedAvante-ProPhase, Inc., Neumora Therapeutics, Neurocrine Biosciences, Novartis, Noven Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Relmada, Sage Therapeutics, Supernus, Sunovion Pharmaceuticals, Inc., Takeda Pharmaceutical Co., Teva Pharmaceutical Industries Ltd., Tris Pharma, and Vanda Pharmaceuticals, Inc.; he has received research grants from AbbVie/Allergan, Acadia Pharmaceuticals, Inc., Alkermes, Axsome Therapeutics, Inc., Biohaven Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Intra-Cellular Therapies, Inc., Janssen Pharmaceuticals, Inc., KemPharm, Lundbeck, Neurocrine Biosciences, Novartis, Noven Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Sage Therapeutics, Supernus, Sunovion Pharmaceuticals, Inc., Takeda Pharmaceutical Co., and Tris Pharma; and he is on the DSMB for COMPASS Pathways and is on the board of the Neuroscience Education Institute.

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