Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study

Am J Psychiatry. 2014 Feb;171(2):160-8. doi: 10.1176/appi.ajp.2013.13070984.


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-├ůsberg 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.

Trial registration: NCT00868699.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Isoindoles / adverse effects
  • Isoindoles / therapeutic use*
  • Lurasidone Hydrochloride
  • Male
  • Middle Aged
  • Placebos
  • Psychiatric Status Rating Scales
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents
  • Isoindoles
  • Placebos
  • Thiazoles
  • Lurasidone Hydrochloride

Associated data