Correlation of MADRS and Q-LES-Q-SF in patients with Bipolar II depression: A post-hoc analysis of an Indian Phase 3 study

Introduction Lumateperone, an atypical antipsychotic drug approved in 2021 for bipolar depression, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors. In India, Quetiapine is one of the approved drugs for use in depressive episodes for bipolar disorder. Objectives This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the correlation of severity of depression assessed via Montgomery-Asberg depression rating scale (MADRS) and quality of life assessed via Quality-of-life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) when treated with Lumateperone 42mg or Quetiapine 300mg. Methods The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a MADRS score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. In this post-hoc analysis, correlation between MADRS and Q-LES-Q-SF were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583] Results This post-hoc analysis included 462 patients [231 each in Test and Comparator]. The baseline demographic characteristics were comparable in between treatment arms. The Pearson’s correlation coefficient between change from baseline in MADRS score and Q-LES-Q-SF score was statistically significant for both treatment arms at Day 42 [Test: -0.192, p=0.0043; Comparator: -0.299, p<0.0001] and the linear regression between 2 arms was not statistically significant (p=0.0853), indicating weak negative correlation between the 2 scales [Figure 1 and Figure 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported. Image 1: Image 2: Conclusions This post-hoc analysis demonstrated that patient with Bipolar II depression when treated with Lumateperone 42mg or Quetiapine 300mg, the reduction in MADRS score is inversely proportional to Q-LES-Q-SF score. Disclosure of Interest A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. G. Goyal: None Declared, S. Mangalwedhe: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, S. Saha Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma