Naltrexone and disulfiram in patients with alcohol dependence and current depression

Department of Psychiatry, Yale University, New Haven, Connecticut, United States
Journal of Clinical Psychopharmacology (Impact Factor: 3.76). 05/2007; 27(2):160-5. DOI: 10.1097/jcp.0b13e3180337fcb
Source: PubMed

ABSTRACT Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression.
Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events.
One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone.
The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.

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    • "However in the present analyses we were able to mitigate the loss of power issue by using repeated measures analyses on up to nine time-points per subject. Lastly the potential influence of naltrexone on both drinking and depression outcomes in this study was not known, although it is now suggested naltrexone has little effect on depressive symptoms (Petrakis et al., 2007). "
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    ABSTRACT: Depression commonly co-occurs with alcohol use disorders but predictors of depression treatment outcome in patients with both conditions are not well established. Outpatients with alcohol dependence and major depression (n=138) were prescribed naltrexone and randomized to citalopram or placebo for 12 weeks, followed by a 12-week naturalistic outcome phase. General linear mixed models examined predictors of Montgomery Asberg Depression Rating Scale (MADRS) score over 24 weeks. Predictors included whether depression was independent or substance-induced, and demographic, alcohol use, and personality variables (Temperament and Character Inventory subscales). Most improvement in drinking and depression occurred between baseline and week 3. During follow-up, patients with substance-induced depression reduced their drinking more and they had better depression outcomes than those with independent depression. However, greater reduction in drinking was associated with better depression outcomes for both independent and substance-induced groups, while antidepressant therapy had no effect for either group. Baseline demographic and alcohol use variables did not predict depression outcomes. Among personality variables, high self-directedness was a strong predictor of better depression outcomes. Subjects were not abstinent at baseline. The influence of naltrexone on depression outcomes could not be tested. Alcohol dependent patients with substance-induced depression have better short term depression outcomes than those with independent depression, but this is largely because they reduce their drinking more during treatment. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 12/2014; 174C:503-510. DOI:10.1016/j.jad.2014.11.052 · 3.71 Impact Factor
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    ABSTRACT: INTRODUCTION Although alcoholism is a severe public health problem having a worldwide impact, there are a limited number of pharmacological interventions used for its treatment. OBJECTIVES To evaluate the contribution of disulfiram use for retention of alcohol-dependent outpatients in treatment with focus on gender. METHODS This is a retrospective cross-sectional study using a sample of 810 alcohol-dependent patients (652 men and 158 women) who attended the clinic between 2000 and 2006. The patients were divided into three groups depending on their treatment retention. RESULTS A greater concentration of men and women who took the aversive medication among the patients remained longer in treatment. CONCLUSION Disulfiram is an instrument that can contribute to improve retention in outpatient treatment, but this approach should be viewed as part of a complex and dynamic therapeutic process.
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    ABSTRACT: Addiction to substances continues to be a significant public health concern in the United States. The following review of current pharmacological treatments discusses a range of substances: nicotine, alcohol, cocaine, and opioids. The goal is to provide an overview of currently available and new pharmacological treatments for substance use disorders, while also addressing the pharmacotherapeutic challenges remaining. The significant advances in pharmacotherapy have had limited utilization, however. For example, naltrexone for alcoholism is infrequently prescribed, buprenorphine for opiates still has relatively few qualified prescribers, and stimulants have no Food and Drug Administration-approved pharmacotherapy. These pharmacotherapies are needed, with the rate of even the relatively uncommon abuse of opiates now rising sharply.
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