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: 3.24). 05/2007; 27(2):160-5. DOI: 10.1097/jcp.0b13e3180337fcb
Source: PubMed


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 · 3.38 Impact Factor
    • "Thus playing an important role in long term management in alcohol de-addiction along with effective psychotherapy and counseling unlike to the writings of Mann and Williams.[22] Other studies supporting for long term DSM management and it being better than other treatment protocols are Petrakis et al,[23] and De Souza.[24] "
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    ABSTRACT: Assessment of safety and efficacy profile of disulfiram (DSM) in the alcoholic de-addiction regimen. a. Assessment of Adverse Drug Reaction (ADR) profile; b. Evaluation of effectiveness of various deaddiction regimen; c. Defaulters and dropouts Fifty-one patients in a de-addiction center were investigated on 0(th) , 30(th) and 60(th) day along with psychiatric evaluation, ADR surveillance was made. Statistical analysis was done thereafter. 125 mg DSM given OD for 2 months. 76.5% patients had taken full course of treatment, 45% didn't complain of any ADR. Of ADR reported 27.4% had drowsiness, 21.4% tiredness, 7.8% skin manifestation. DSM is the main drug among naltrexone, acamprosate, nalmefene and other drugs used in alcoholic de-addiction. Relative and effectiveness is lost by the degree of dropouts and hence relapses. Low-dose DSM had decreased adverse effects with 76.5% patients taking the full course of treatment. DSM alters liver functions as there were significant changes in the lab parameters of SGPT(P=0.007), SGOT(P=0.001), GGT(P=<0.001) between first and third samples. Occurrence of ADR is not the cause of default; patients find it confusing to differentiate between the symptoms of alcohol withdrawal and those due to ADR of DSM.
    Indian Journal of Psychiatry 03/2011; 53(1):25-9. DOI:10.4103/0019-5545.75557
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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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