THE EFFICACY OF LURASIDONE IN BIPOLAR I DEPRESSION: SUBGROUP ANALYSIS BY SEVERITY OF ANXIETY SYMPTOMS

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<0.001) and the 80–120 mg/day group (- 15.2, p<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.