Acute Effects of Disulfiram on Anxiety Levels of Chronic
Alcoholics

Snyder, Scott W.; Keeler, Martin H.

doi:10.1159/000468474

Cited by 11 publications

(14 citation statements)

References 10 publications

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“…Disulfiram, an irreversible ALDH-1 and ALDH-2 inhibitor, does not appear to have anxiolytic properties in humans (Goyer et al, 1984; Snyder and Keeler, 1981). This difference may be related, in part, to the fact that disulfiram and its metabolites inhibit many sulfhydryl and metal-containing enzymes while CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 only.…”

Section: Discussionmentioning

confidence: 99%

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A selective ALDH-2 inhibitor reduces anxiety in rats

Overstreet¹,

Knapp²,

Breese³

et al. 2009

Pharmacology Biochemistry and Behavior

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CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anxiety-like behavior in naïve Fawn-Hooded rats, repeated alcohol-withdrawalinduced anxiety, restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted anxiety in all models except that produced by the 5-HT 2C agonist, mCPP. CVT-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawalinduced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA-benzodiazepine system.

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Section: Discussionmentioning

confidence: 99%

“…1), might also have anxiolytic effects. There is no known literature on the potential anxiolytic effects of ALDH-2 inhibitors (Snyder and Keeler, 1981) nor has a link been established between ALDH-2 inhibitors and benzodiazepines. Thus, this study is breaking new ground.…”

Section: Introductionmentioning

confidence: 99%

A selective ALDH-2 inhibitor reduces anxiety in rats

Overstreet¹,

Knapp²,

Breese³

et al. 2009

Pharmacology Biochemistry and Behavior

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show abstract

“…The authors noted that open label designs are more appropriate than double-blind trials in studying the effects of disulfiram, because expectancy plays an integral role in the therapeutic effects of this medication. Disulfiram does not appear to have any consistent direct effects on anxiety or mood (16, 17). …”

Section: Introductionmentioning

confidence: 91%

Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study

Bogenschutz

Bhatt

Bohan

et al. 2016

The American Journal of Drug and Alcohol Abuse

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Background Anxiety is common among persons with alcohol use disorder during early abstinence from alcohol. Although benzodiazepines are effective for short-term treatment of anxiety, they are rarely used beyond acute detoxification due to concerns about misuse or interactions with alcohol. Objectives We conducted an open-label trial to explore the effects of coadministering lorazepam and disulfiram to alcohol dependent patients with anxiety disorder symptoms. The rationale for this model is to minimize the risks of the benzodiazepine, while also potentially enhancing adherence to disulfiram. Methods Forty-one participants with DSM-IV alcohol dependence who also met syndromal criteria for anxiety disorder with or without co-occurring major depressive syndrome initiated treatment with lorazepam (starting dose 0.5 mg three times daily) and disulfiram (starting dose 500mg three times weekly). Participants received 16 weeks of monitored pharmacotherapy with manualized medical management. Results Adherence to treatment decreased steadily with time (85.4% at 4 weeks, 36.6% at 16 weeks). Participants showed significant increases in percent abstinent days during treatment and at 24 week follow-up. Large reductions in anxiety, depression, and craving were observed during treatment, and improvement remained significant at 24 weeks. Duration of adherence with disulfiram strongly predicted abstinence at 16 weeks. There was no evidence of misuse of lorazepam or dose escalation during the study. Conclusion Lorazepam can be safely used for short-term treatment of anxiety in combination with disulfiram treatment of alcohol use disorder. Controlled trials are necessary to determine the effects of lorazepam on anxiety, retention in treatment, and drinking in this context.

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“…Because the manufacturing and quality of melatonin is not currently regulated in the U.S., the melatonin receptor agonist, ramelteon, may be a better candidate for study. Disulfiram causes drowsiness more frequently than placebo, 96 but it decreases total REM time 97 and is compromised by low compliance rates. 96,98 Nonpharmacological treatments for insomnia A recent NIH State-of-the-Science conference on the Manifestations and Management of Chronic Insomnia in Adults recently concluded that cognitive-behavioral treatment for insomnia (CBT-I) benefits 70-80% of non-alcoholic insomnia patients and has more sustained benefits than medications.…”

Section: Antidepressants-a Number Of Antidepressants Have Sedative Efmentioning

confidence: 99%

Treatment Options for Sleep Disturbances During Alcohol Recovery

Arnedt

Conroy

Brower

2007

Journal of Addictive Diseases

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Sleep disturbances are extremely common in the early stages of recovery from alcohol dependence and may persist for several months despite continued abstinence. Studies indicate that sleep disturbances independently increase the risk for relapse to alcohol, suggesting that targeting these problems during recovery may support continued abstinence. However, there is limited information in the addiction literature about available and effective treatments for sleep disturbances in recovering alcoholic patients. The primary goals of this article are to describe the phenomenology of sleep disturbances during recovery from alcohol dependence, to outline the evidence linking sleep problems with alcohol relapse, and to describe available pharmacological and nonpharmacological treatment options, including the evidence regarding their efficacy in recovering alcoholic patients. Recommendations for future research are provided along with special considerations for treating insomnia in this population, including avoiding cross-dependent sedatives, such as benzodiazepines and benzodiazepine receptor agonists (BzRAs). alcohol; alcoholism; sleep; insomnia; treatment; pharmacological; nonpharmacological; cognitivebehavioral treatment Insomnia is a complaint of difficulties falling asleep, frequent and/or prolonged awakenings, and/or consistently unrefreshing sleep that occurs despite adequate sleep opportunity. Insomnia is exceedingly common: as many as 1/3 of adults report experiencing persistent insomnia symptoms during the year. [1][2][3][4] Insomnia symptoms persisting for more than one month that are associated with daytime impairment and/or psychological distress define an insomnia disorder, which occurs in one in ten individuals. Persistent insomnia is associated with wide ranging adverse consequences, including decreased quality of life, increased risk for psychiatric disturbances, increased work absenteeism, and poor interpersonal functioning. 1,2,5,6 Among patients in recovery from alcohol dependence, insomnia complaints are especially frequent and may persist for weeks to months post-abstinence. [7][8][9][10][11][12][13][14] Of particular importance, untreated insomnia may interfere with recovery from the primary alcohol addiction and contribute to relapse within the first several months of recovery. 12,15,16 Thus, treating insomnia in recovering alcoholic patients may aid in their recovery and support continued abstinence. Keywords NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDespite the putative importance of sleep in the recovery process, there is limited information in the addiction literature about appropriate treatment options for insomnia during recovery. This may exist for a variety of reasons: clinicians assume that co-morbid sleep problems will remit with treatment of the primary alcohol condition; sleep problems are de-emphasized as relatively less important in the early stages of treatment for alcohol dependence; or physicians may be reluctant to address sleep problem...

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Acute Effects of Disulfiram on Anxiety Levels of Chronic Alcoholics

Cited by 11 publications

References 10 publications

A selective ALDH-2 inhibitor reduces anxiety in rats

A selective ALDH-2 inhibitor reduces anxiety in rats

Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study

Treatment Options for Sleep Disturbances During Alcohol Recovery

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