A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II)

J Clin Psychiatry. 2010 Feb;71(2):163-74. doi: 10.4088/JCP.08m04942gre. Epub 2010 Jan 26.

Abstract

Objective: The aim of this study was to evaluate the efficacy and tolerability of quetiapine and paroxetine monotherapy for major depression in bipolar disorder.

Method: 740 patients (478 bipolar I, 262 bipolar II) with major depressive episodes (DSM-IV) were randomly assigned to quetiapine 300 mg/d (n = 245), quetiapine 600 mg/d (n = 247), paroxetine 20 mg/d (n = 122), or placebo (n = 126) for 8 weeks. The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from May 2005 to May 2007.

Results: Mean MADRS score change from baseline at 8 weeks was -16.19 for quetiapine 300 mg, -16.31 for quetiapine 600 mg, -13.76 for paroxetine, and -12.60 for placebo (P < .001 for both quetiapine doses, P = .313 for paroxetine, vs placebo). Quetiapine-treated (both doses), but not paroxetine-treated, patients showed significantly greater improvements (P < or = .05) in most secondary outcomes measures at week 8 versus the placebo group. Paroxetine significantly improved Hamilton Anxiety Rating Scale scores versus placebo (P < .05) but not MADRS or Hamilton Depression Rating Scale (HDRS) scores. Both quetiapine doses were associated with greater improvements than paroxetine for MADRS and HDRS scores. The most common adverse events were dry mouth, somnolence, sedation, and dizziness with quetiapine (both doses) and dry mouth, sedation, headache, insomnia, and nausea with paroxetine. The incidence of treatment-emergent mania/hypomania was lower with quetiapine compared with paroxetine and placebo.

Conclusions: Quetiapine (300 or 600 mg/d), but not paroxetine, was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated.

Trial registration: clinicaltrials.gov Identifier: NCT00119652.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Antimanic Agents / adverse effects
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / adverse effects
  • Paroxetine / therapeutic use*
  • Placebos
  • Psychiatric Status Rating Scales
  • Quetiapine Fumarate
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Antimanic Agents
  • Dibenzothiazepines
  • Placebos
  • Quetiapine Fumarate
  • Paroxetine

Associated data

  • ClinicalTrials.gov/NCT00119652