A Double-Blind, Placebo-Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol Dependence

Authors

  • Mary Stedman,

    1. From Stedman Clinical Trials (MS), Tampa, Florida; University of Pennsylvania School of Medicine (HMP), Philadelphia, Pennsylvania; The University of Texas Southwestern Medical Center (ESB), Dallas, Texas; Case Western Reserve University, University Hospitals of Cleveland (MK, JRC), Cleveland, Ohio; AstraZeneca Pharmaceuticals LP (SR), Wilmington, Delaware.
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  • Helen M. Pettinati,

    1. From Stedman Clinical Trials (MS), Tampa, Florida; University of Pennsylvania School of Medicine (HMP), Philadelphia, Pennsylvania; The University of Texas Southwestern Medical Center (ESB), Dallas, Texas; Case Western Reserve University, University Hospitals of Cleveland (MK, JRC), Cleveland, Ohio; AstraZeneca Pharmaceuticals LP (SR), Wilmington, Delaware.
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  • E. Sherwood Brown,

    1. From Stedman Clinical Trials (MS), Tampa, Florida; University of Pennsylvania School of Medicine (HMP), Philadelphia, Pennsylvania; The University of Texas Southwestern Medical Center (ESB), Dallas, Texas; Case Western Reserve University, University Hospitals of Cleveland (MK, JRC), Cleveland, Ohio; AstraZeneca Pharmaceuticals LP (SR), Wilmington, Delaware.
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  • Margaret Kotz,

    1. From Stedman Clinical Trials (MS), Tampa, Florida; University of Pennsylvania School of Medicine (HMP), Philadelphia, Pennsylvania; The University of Texas Southwestern Medical Center (ESB), Dallas, Texas; Case Western Reserve University, University Hospitals of Cleveland (MK, JRC), Cleveland, Ohio; AstraZeneca Pharmaceuticals LP (SR), Wilmington, Delaware.
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  • Joseph R. Calabrese,

    1. From Stedman Clinical Trials (MS), Tampa, Florida; University of Pennsylvania School of Medicine (HMP), Philadelphia, Pennsylvania; The University of Texas Southwestern Medical Center (ESB), Dallas, Texas; Case Western Reserve University, University Hospitals of Cleveland (MK, JRC), Cleveland, Ohio; AstraZeneca Pharmaceuticals LP (SR), Wilmington, Delaware.
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  • Shane Raines

    1. From Stedman Clinical Trials (MS), Tampa, Florida; University of Pennsylvania School of Medicine (HMP), Philadelphia, Pennsylvania; The University of Texas Southwestern Medical Center (ESB), Dallas, Texas; Case Western Reserve University, University Hospitals of Cleveland (MK, JRC), Cleveland, Ohio; AstraZeneca Pharmaceuticals LP (SR), Wilmington, Delaware.
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  • Previous presentations: 48th Annual New Drug Clinical Evaluation Unit Meeting. May 27–30, 2008; Phoenix, Arizona, USA; Annual Scientific Meeting of the Research Society on Alcoholism. June 28–July 2, 2008; Washington, DC, USA.

  • Clinical trial registration information: Efficacy and Safety of Quetiapine Fumarate (SEROQUEL®) in the Treatment of Alcohol Dependency in Patients With Bipolar Disorder (D144AL00002). Available at: http://clinicaltrials.gov/ct2/show/NCT00114686?term=D144AL00002&rank=1

Reprint requests: Mary Stedman, MD, Stedman Clinical Trials, 3212 Cove Bend Dr., Tampa, FL 33613; Tel.: 813-971-8311; Fax: 813-971-0862; E-mail: marystedman@tampabay.rr.com

Abstract

Background:  This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence.

Methods:  Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score.

Results:  Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was −0.36 with quetiapine and −0.36 with placebo (= 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine.

Conclusions:  The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence.

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