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Lurasidone Monotherapy in the Treatment of Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Study
Antony Loebel, M.D.; Josephine Cucchiaro, Ph.D.; Robert Silva, Ph.D.; Hans Kroger, M.P.H., M.S.; Jay Hsu, Ph.D.; Kaushik Sarma, M.D.; Gary Sachs, M.D.
Am J Psychiatry 2014;171:160-168. doi:10.1176/appi.ajp.2013.13070984
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Dr. Sachs has been a consultant for Sunovion, Otsuka, Johnson & Johnson, and Grunenthal, has stock/other financial relationship with Collaborative Care Initiative, and is an employee of Bracket. Drs. Loebel, Cucchiaro, Silva, Kroger, Hsu, and Sarma are full-time employees of Sunovion Pharmaceuticals, Inc.

This study was sponsored by Sunovion Pharmaceuticals, Inc.

Clinicaltrials.gov identifier: NCT00868699

From Sunovion Pharmaceuticals, Inc., Fort Lee, N.J., and Marlborough, Mass.; and the Bipolar Clinic and Research Program, Massachusetts General Hospital, Boston.

Presented in part at the 165th annual meeting of the American Psychiatric Association, Philadelphia, May 5–9, 2012; the 51st annual meeting of the American College of Neuropsychopharmacology, Hollywood, Fla., December 2–6, 2012; and the 10th International Conference on Bipolar Disorders, Miami Beach, June 13–16, 2013.

Address correspondence to Dr. Loebel (Antony.Loebel@sunovion.com).

Copyright © 2014 by the American Psychiatric Association

Received July 27, 2013; Revised September 09, 2013; Accepted September 10, 2013.

Abstract

Objective  The authors evaluated the efficacy and safety of lurasidone in the treatment of patients with major depressive episodes associated with bipolar I disorder.

Method  Patients were randomly assigned to receive double-blind treatment with lurasidone (20–60 mg/day [N=166] or 80–120 mg/day [N=169]) or placebo (N=170) for 6 weeks. Primary and key secondary endpoints were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and depression severity score on the Clinical Global Impressions scale for use in bipolar illness (CGI-BP), respectively.

Results  Lurasidone treatment significantly reduced mean MADRS total scores at week 6 for both the 20–60 mg/day group (−15.4; effect size=0.51) and the 80–120 mg/day group (−15.4; effect size=0.51) compared with placebo (−10.7). Similarly, lurasidone treatment resulted in significantly greater endpoint reduction in CGI-BP depression severity scores for both the 20–60 mg/day group (−1.8; effect size=0.61) and the 80–120 mg/day group (−1.7; effect size=0.50) compared with placebo (−1.1). Both lurasidone groups also experienced significant improvements compared with placebo in anxiety symptoms and in patient-reported measures of quality of life and functional impairment. Discontinuation rates due to adverse events were similar in the 20–60 mg/day (6.6%), 80–120 mg/day (5.9%), and placebo (6.5%) groups. The most frequent adverse events associated with lurasidone were nausea, headache, akathisia, and somnolence. Minimal changes in weight, lipids, and measures of glycemic control were observed with lurasidone.

Conclusion  Monotherapy with lurasidone in the dosage range of 20–120 mg/day significantly reduced depressive symptoms in patients with bipolar I depression. Lurasidone was well tolerated, with few changes in weight or metabolic parameters.

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FIGURE 1. Patient Disposition in a Double-Blind, Randomized, Placebo-Controlled Trial of Lurasidone for Bipolar I Depression

FIGURE 2. Change From Baseline in Key Efficacy Measures

a Mean scores at baseline were 30.3 (SD=5.0), 30.6 (SD=4.9), and 30.5 (SD=5.0) for the lurasidone 20–60 mg, lurasidone 80–120 mg, and placebo groups, respectively.

b Mean scores at baseline were 4.52 (SD=0.62), 4.55 (SD=0.64), and 4.48 (SD=0.61) for the lurasidone 20–60 mg, lurasidone 80–120 mg, and placebo groups, respectively.

* p<0.05; ** p<0.01; *** p<0.001

FIGURE 3. Baseline-to-Endpoint Change Scores on Additional Secondary Efficacy Measures (intent-to-treat population)a

a LOCF=last observation carried forward.

* p<0.05; ** p<0.01; *** p<0.001

Anchor for Jump
TABLE 1.Demographic and Clinical Characteristics at Baseline (intent-to-treat population) of Patients in a Double-Blind, Randomized, Placebo-Controlled Trial of Lurasidone for Bipolar I Depression
Anchor for Jump
TABLE 2.Adverse Events (incidence ≥5%, with incidence greater for the lurasidone group versus placebo; safety population)
Table Footer Note

a Drooling, dystonia, muscle rigidity, oromandibular dystonia, parkinsonism, torticollis, and tremor.

Anchor for Jump
TABLE 3.Baseline to Endpoint Change in Weight and Laboratory Parameters (last observation carried forward)a
Table Footer Note

a Both confirmed and nonconfirmed fasting values are presented for metabolic parameters.

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