Naltrexone and disulfiram in patients with alcohol dependence and current depression
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.
SourceAvailable from: Avinash Desousa[Show abstract] [Hide abstract]
ABSTRACT: Disulfiram remains a viable option as a treatment for alcohol dependence and has been shown in recent studies to be successful in treating patients with alco-hol dependence in a manner that is superior to both naltrexone and acamprosate. It is also useful in dual diagnosis patients and those with co-morbid cocaine and alcohol dependence. Although disulfiram's me-chanism of action in alcohol dependence was long thought to be its effects as a psychological deterrent, more recent studies have uncovered potential anti-craving effects as well. Recent reviews exhort to the importance of supervised disulfiram therapy in high-lighting many of the potential and unique benefits of disulfiram. The present article will review the major clinical trials of disulfiram spanning nearly 60 years. It also discusses the usage of disulfiram across diverse populations along with monitoring for compliance and various adverse effects that may be encountered. The paper also reviews certain studies on long acting di-sulfiram therapy, recent comparative trials of disul-firam and its use in alcohol dependence. The review concludes with the role of disulfiram in the present day and long-term pharmacotherapy of alcohol de-pendence along with future research needs in this area.Open Journal of Psychiatry 01/2014; 4(1):43-52. DOI:10.4236/ojpsych.2014.41007
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ABSTRACT: Almost 10% of the world's population is affected by alcohol use disorders, and the treatment of alcohol dependence (AD) still remains a challenge. Patients with AD can differ in many traits. Three drugs (disulfiram, naltrexone, and acamprosate) have been approved by the FDA for the treatment of AD, and in some European countries sodium oxybate is also approved for this purpose. Combined pharmacological therapy has not provided such convincing results. Considering the fact that the "ideal" and effective drug for all types of alcoholic patients does not exists, the future challenge will be to identify a personalized approach. Recent data has shown that this objective can be achieved by investigating the genetic variability of the patient. Moreover, the use of replacement molecules can probably be considered an advantageous therapeutic opportunity (i.e. sodium oxybate). In addition, reduction of alcohol consumption is increasingly accepted as a viable treatment goal, and the use of nalmefene "as-needed" (a pharmacological approach similar to naltrexone, but, possibly, with lower hepatotoxicity) may help in the treatment of AD. Thus, it is important to stress that a pharmacological approach to treat AD should be preceded by the definition of patient characteristics; this may help in the choice of the most appropriate drug and it can be done more easily when more pharmacological options approved for the treatment of AD are also available.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 10/2013; DOI:10.1016/j.euroneuro.2013.10.004 · 3.68 Impact Factor
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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 · 3.76 Impact Factor