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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    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: Ethylglucuronid (EtG) wurde bereits früher in Serum, Urin, Haaren und in Leichengewebe nachgewiesen und hat sich als spezifischer Marker für vorausgegangenen Alkoholkonsum etabliert. In dieser Arbeit wurde erstmalig Ethylsulfat (EtS) gemeinsam mit Ethylglucuronid aus Serum von 21 Probanden (insgesamt 105 Proben) zur retrospektiven Beurteilung von Alkoholkonsum in einer drei-monatigen klinischen Medikamentenstudie mit alkoholkranken Probanden bestimmt. Es zeigte sich eine gute Korrelation zwischen Ethylglucuronid und Ethylsulfat (p < 0,001), wobei die zusätzliche Bestimmung von Ethylsulfat nur in einem Fall einen zusätzlichen Informationsgewinn erbrachte. Im Verlauf des 12-wöchigen Versuchszeitraums ergaben sich bei den Probanden der Verumgruppe tendenziell abfallende Konzentrationen. Dies deckt sich mit den Ergebnissen der Studie, die signifikant niedrigere γ GT Konzentrationen im Verlauf aufzeigte und mit zusätzlich ermittelten CDT-Konzentrationen, die ebenfalls im Verlauf der Studie abfielen. Eine Korrelation von EtG und EtS mit CDT ergab sich jedoch nicht. Weiterhin wurden von 38 Probanden (20 Verum, 18 Placebo) Blutserumproben während der Topiramatstudie zu unterschiedlichen Zeitpunkten (0 – 12 Wochen) auf Ethylglucuronid analysiert. In der Placebogruppe konnte in 57 % der Proben EtG nachgewiesen werden. In der Topiramatgruppe wurde EtG in 24 % der Proben nachgewiesen. Eine weitere Tendenz wurde durch Betrachtung von Mittelwerten der ersten bzw. letzten beiden Proben herausgearbeitet. In der Verumgruppe zeigte sich bei 50 % der Probanden eine Reduktion und bei 10 % eine Erhöhung der Mittelwerte im Verlauf. Bei 40 % der Probanden wurde zu keinem Zeitpunkt EtG nachgewiesen. In der Placebogruppe konnte bei 40 % der Probanden eine Reduktion und bei 50 % eine Erhöhung der Mittelwerte im Verlauf aufgezeigt werden. Bei einem Probanden (ca. 5 %) ergab sich keine Veränderung der Mittelwerte, und ein weiterer Proband (ca. 5 %) hatte zu keinem Zeitpunkt nachweisbare EtG-Konzentrationen. Tendenziell enthielten die Proben der Gruppe mit Topiramat-Medikation geringere EtG Konzentrationen, bzw. es wurde weniger häufig EtG nachgewiesen. Durch die zusätzliche Bestimmung von Ethylglucuronid konnten bei ca. 10 % der untersuchten Probanden falsche Angaben im MALT bei negativem Nachweis von CDT aufgedeckt werden. Unter diesem Gesichtspunkt müssen die Angaben der Probanden bezüglich ihres Trinkverhaltens neu bewertet werden. Ethyl glucuronide (EtG) had been already proven earlier in serum, urine, hair and corpse tissue and was established as a specific marker for preceded alcohol consumption. In this dissertation ethyl sulfate (EtS) was detected for the first time together with ethyl glucuronide out of serum from 21 test persons (overall 105 samples) to retrospectively evaluate the alcohol consumption in a three month clinical medicine study with alcoholics. A good correlation showed up between ethyl glucuronide and ethyl sulfate (p < 0,001), whereby the additional detection of ethyl sulfate led only in one case to additional information. Within this study, that lasted 12 weeks decreasing concentrations for EtG and EtS were detected in the verum group compared with the placebo group. This fits to the results of the study which showed significantly lower γ-GT concentrations in the process and with additionally determined CDT concentrations, which also decreased during the study. However a correlation between EtG and EtS with CDT did not result. Furthermore blood serum samples from 38 test persons (20 verum, 18 placebo) were analized on ethyl glucuronide during the topiramat study at different times (0- 12 weeks). As a result EtG was detected in 57% of the placebo group samples. Within the topiramat group EtG was detected in 24% of the samples. Another trend could be shown by comparing the average of the results of the first two samples respectively the last two samples of the lasted 12 weeks study. A reduction of the average could be figured out in 50% of the verum group and in 10% an increase of the average, and 40% of the test persons did not show positive results of EtG at any time. In the placebo group, 40% of the test persons showed a reduction and 50% an increase of the average during the study process. One test person (5%) had no change of the average and one test person (5%) did not show positive results of EtG at any time. Tendencially the samples of the group with topiramat medication contained less EtG concentration, respectively EtG was detected less frequently. The additional detection of EtG discovered in 10% of the examined persons wrong data in MALT with negative CDT concentrations at the same time. Therefore the data of the test persons concerning their drinking behavior has to be evaluated again.
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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.