THE EFFICACY OF LURASIDONE IN BIPOLAR I DEPRESSION: SUBGROUP ANALYSIS BY SEVERITY OF ANXIETY SYMPTOMS
Authors: Inoue *Takeshi , Masuda Takahiro , Sano Fumiya , Maruyama Hidenori 
Published: February 2025

Abstract

Background
Anxiety symptoms are commonly seen in patients with bipolar depression, and are reported to the relationship to more persistent depressive symptoms and increased suicidal ideation.1,2)

Aims & Objective
To examine the effect of anxiety severity on the efficacy of lurasidone in patients with bipolar I depression.

Method
In this post-hoc analysis, data were pooled from two 6-week phase 3, double-blind, placebo- controlled studies of lurasidone monotherapy (20-60 mg/day or 80-120 mg/day) in patients with bipolar I depression3,4) excluding rapid-cycling. Patients were dichotomized into two groups: severe and non-severe anxiety. Severe anxiety was defined as baseline Hamilton Anxiety Rating Scale (HAM-A) total score 18 or more.5) Least square (LS) mean changes from baseline to week 6 in Montgomery/Asberg Depression Rating Scale (MADRS) total score were compared between lurasidone and placebo by mixed- effects model for repeated measures. Number needed to treat (NNT) for response (50% or more reduction from baseline in MADRS total score) was calculated.

Results
In the severe anxiety group (n=346), LS mean change from baseline to week 6 in MADRS total score was significantly greater for the lurasidone 20-60 mg/day group (-15.5; p=0.004) compared to placebo (-11.4). LS mean change from baseline to week 6 on the MADRS total score was numerically superior to placebo for the lurasidone 80-120 mg/day group but not statistically significant (-13.5; p=0.164). NNT to achieve a response was 5 (95%CI: 3,13) in the lurasidone 20-60 mg/day group. In the non-severe anxiety group (n=576), lurasidone treatment significantly reduced LS mean MADRS total scores at week 6 for both the 20–60 mg/day group (-15.0, p&lt;0.001) and the 80–120 mg/day group (- 15.2, p&lt;0.001) compared with placebo (-10.7). NNTs were 5 (95%CI: 3,10) in lurasidone 20-60 mg/day and 6 (95%CI: 3,10) in lurasidone 80-120 mg/day groups.

Discussion and Conclusion
In this post-hoc analysis, the results suggest that lurasidone 20-60 mg/day may improve depressive symptoms in patients with bipolar I depression regardless of their anxiety level.

References
1)Coryell W, Fiedorowicz JG, Solomon D, Leon AC, Rice JP, Keller MB (2012) Effects of anxiety on the long-term course of depressive disorders. Br J Psychiatry 200:210-5.
2)Young LT, Cooke RG, Robb JC, Levitt AJ, Joffe RT (1993) Anxious and nonanxious bipolar disorder. J Affect Disord 29:49-52.
3)Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G (2014) Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry.171:160-8.
4)Kato T, Ishigooka J, Miyajima M, Watabe K, Fujimori T, Masuda T, Higuchi T, Vieta E (2020) Double- blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression. Psychiatry Clin Neurosci 74:635-644.
5)Tohen M, Calabrese J, Vieta E, Bowden C, Gonzalez-Pinto A, Lin D, Xu W, Corya S (2007) Effect of comorbid anxiety on treatment response in bipolar depression. J Affect Disord. 104:137-46.