A Randomized, Double-Blind, Placebo-Controlled Add-On Trial of Quetiapine in Outpatients With Bipolar Disorder and Alcohol Use Disorders

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-8849, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 02/2008; 69(5):701-5. DOI: 10.4088/JCP.v69n0502
Source: PubMed


Alcohol dependence is extremely common in patients with bipolar disorder, and it is associated with unfavorable outcomes, including treatment nonadherence, violence, and cognitive impairment. However, few treatment trials have been conducted in this population. Quetiapine is an atypical antipsychotic medication that is used to treat the mood symptoms of bipolar disorder. In this study, the efficacy of quetiapine in reducing alcohol use and improving mood symptoms was assessed in patients with bipolar disorder and alcohol abuse or dependence.
One hundred fifteen outpatients with bipolar disorder and alcohol abuse or dependence were randomly assigned to 12 weeks of quetiapine (titrated to 600 mg/day) add-on therapy or placebo. Alcohol use and mood were assessed. The study was conducted from November 2002 to September 2005.
One hundred two participants (49% with bipolar I disorder, 82% depressed, and 97% with alcohol dependence) returned for at least 1 postbaseline assessment and were used in the random regression analysis. No statistically significant between-group differences were found on alcohol use measures or the Young Mania Rating Scale. However, based on a random regression analysis, scores on the Hamilton Rating Scale for Depression (HAM-D) decreased statistically significantly more in the quetiapine than in the placebo group during the trial (p < .05). The between-group difference was largely due to differences in HAM-D scores during the first 6 weeks of the trial, with the placebo group showing greater improvement during the second half of the trial.
Quetiapine therapy was associated with a statistically significant decrease in depressive symptoms, but not alcohol use, in patients with bipolar disorder and alcohol dependence (p < .05).

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    • "Drinks per day during the trial for the quetiapine and placebo groups. as compared to placebo (Brown et al., 2008). However, a multisite study of quetiapine in this population did not find a significant difference between treatment groups on the Montgomery-Asberg Depression Rating Scale (Stedman et al., 2010). "
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    ABSTRACT: Background: Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study. Methods: Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model. Results: Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups. Conclusions: Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence.
    No preview · Article · Jun 2014 · Alcoholism Clinical and Experimental Research
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    • "An RCT comparing quetiapine (303 + 152 mg/day) with risperidone (3.1 + 1.2 mg/day) reported that both medications improved psychiatric symptoms and stimulant cravings (Nejtek et al., 2008) (Ib). An RCT of add-on quetiapine (600 mg/day) found no improvement in alcohol use or craving in those with bipolar disorder and alcohol abuse or dependence (Brown et al., 2008) (Ib). An open trial that included patients with alcohol dependence and bipolar disorder (n = 10), or schizoaffective disorder (n = 2) and/or borderline personality disorder (n = 10) found that quetiapine alone improved psychiatric symptoms, and decreased alcohol consumption and craving (Martinotti et al., 2008) (IIb). "
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    ABSTRACT: The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.
    Full-text · Article · May 2012 · Journal of Psychopharmacology
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    • "However, it is important to note that positive clinical trials involving dually diagnosed patients have been scarce, and attempts to replicate such positive findings have not been uniformly successful. For example, though Brown et al. (2008) found that quetiapine reduced depressive symptoms in bipolar alcoholics, these findings were not replicated in a subsequent multi-site clinical trial (Stedman et al., 2010). In contrast, our results regarding the impact of anxiety disorders on clinical outcomes are largely consistent with previous investigations. "
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    ABSTRACT: Despite the high prevalence and detrimental impact of alcoholism on bipolar patients, the diagnostic and treatment factors associated with better or worse clinical outcomes in alcohol-dependent patients with bipolar disorder are not well understood. The present study investigated the prospective impact of baseline psychiatric comorbidities and treatment regimens on clinical outcomes in bipolar alcoholics. Data were drawn from an 8-week randomized controlled clinical trial of acamprosate for individuals (n=30) with co-occurring bipolar disorder and alcohol dependence. Depressive and manic symptoms, and alcohol craving and consumption were monitored longitudinally using standardized instruments. Path analysis was used to estimate the prospective associations between patient characteristics and outcomes. More than 50% of patients were diagnosed with at least one anxiety (76.7%) or drug dependence disorder (60.0%). Comorbid anxiety disorders were prospectively associated with increased depressive symptoms and alcohol use. Participants were prescribed an average of 2.6 psychotropic medications at baseline. Antipsychotics and anticonvulsants were prospectively associated with increased alcohol use; anticonvulsants and benzodiazepines were associated with increased alcohol craving. Antidepressants were associated with increased depressive symptoms. Conversely, lithium was associated with decreased alcohol craving and depressive symptoms. The findings from the present study suggest areas for future research in this population.
    Full-text · Article · Jun 2011 · Psychiatry Research
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