A Double-Blind, Placebo-Controlled Trial to Assess the Efficacy of Quetiapine Fumarate XR in Very Heavy-Drinking Alcohol-Dependent Patients

Authors

  • Raye Z. Litten,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Joanne B. Fertig,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Daniel E. Falk,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Megan L. Ryan,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Margaret E. Mattson,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Joseph F. Collins,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Cristin Murtaugh,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Domenic Ciraulo,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Alan I. Green,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Bankole Johnson,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Helen Pettinati,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Robert Swift,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Maryam Afshar,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Mary F. Brunette,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Nassima A.-D. Tiouririne,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Kyle Kampman,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • Robert Stout,

    1. From the Division of Treatment and Recovery Research (RZL, JBF, DEF, MLR), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Center for Behavioral Health Statistics and Quality (MEM), SAMHSA, Rockville, Maryland; Cooperative Studies Program Coordinating Center (JFC, CM), VA Maryland Health Care System, Perry Point, Maryland; Boston University School of Medicine (DC, MA), Boston, Massachusetts; Department of Psychiatry (AIG), Dartmouth Medical School (DHMC), Lebanon, New Hampshire; Department of Psychiatric Medicine (BJ), University of Virginia, Charlottesville, Virginia; University of Pennsylvania Treatment Research Center (HP, KK), Philadelphia, Pennsylvania; Center for Alcohol and Addiction Studies (RS), Brown University, Providence, Rhode Island; Psychopharmacology Research Group (MFB), Dartmouth Medical School, Concord, New Hampshire; University of Virginia Center for Addiction Research and Education (NA-DT), Richmond, Virginia; and Decision Sciences Institute/PIRE (RS), Pawtucket, Rhode Island.
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  • the NCIG 001 Study Group

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    • See Appendix for authors in NCIG 001 Study Group.


Reprint requests: Daniel E. Falk, Division of Treatment and Recovery Research, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2040, Bethesda, MD 20892; Tel.: 301-443-0788; Fax: 301-443-8774; E-mail: falkde@mail.nih.gov

Abstract

Background:  Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol-dependent population of very heavy drinkers.

Methods:  In this double-blind, placebo-controlled trial, 224 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization.

Results:  No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy-drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%).

Conclusions:  This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy-drinking alcohol-dependent patients.

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