NEWS HIGHLIGHTSMedia Articles Related to Disulfiram
Alkermes Initiates Phase 2 Clinical Study Of ALKS 33 For The Treatment Of Alcohol Dependence
Source: Alcohol / Addiction / Illegal Drugs News From Medical News Today [2009.11.19]
Alkermes, Inc. (NASDAQ: ALKS) announced the initiation of a phase 2 clinical study of ALKS 33, an investigational oral opioid modulator for the potential treatment of alcohol dependence and other central nervous system disorders. The study will assess the safety and efficacy of multiple doses of ALKS 33 in patients with alcohol dependence and is designed to further define the clinical profile of ALKS 33.
Published Studies Related to Disulfiram
A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence. [2008.05]
BACKGROUND: This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence... CONCLUSION: There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.
A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence. [2007.11.17]
BACKGROUND: This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence... CONCLUSION: There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.
Disulfiram and low nickel diet in the management of hand eczema: a clinical study. [2006.03]
BACKGROUND: Hand eczema due to nickel sensitivity is a challenging task for the dermatologist. The average human diet provides sufficient amount of nickel, which acts as a provocating factor in nickel-sensitive individuals. When such patients are treated with steroid or other immunosuppressives, only short-term remission is obtained. This is because unless the dietary intake of nickel is minimized and the existing amount of nickel in the body of the sensitized individual is depleted, long-term remission is unlikely. AIM: To evaluate the efficacy of oral disulfiram, a nickel-chelating agent and low nickel diet (LND) in reducing the clinical symptoms and preventing frequent relapse of hand eczema in nickel-sensitive individuals... CONCLUSION: Low nickel diet and short course of oral disulfiram therapy can be considered a good option for the control of chronic hand eczema in nickel-sensitive individuals.
Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders. [2005.05.15]
CONCLUSIONS: These data suggest a modest advantage for the use of disulfiram and naltrexone for this group of dually diagnosed alcohol-dependent individuals but did not suggest an advantage in the combination.
A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of alcohol dependence. [2004.11]
AIMS: To compare the efficacy of naltrexone and disulfiram in preventing an alcoholic relapse in routine clinical practice in an Indian metropolis... CONCLUSIONS: Disulfiram is superior to naltrexone in preventing a relapse among alcohol-dependent men with family support. Comparison between these treatments in other settings and in different types of alcoholics is warranted.
Clinical Trials Related to Disulfiram
Clinical Efficacy of Disulfiram in LAAM-Maintained Cocaine Abusers [Completed]
This 18-week, randomized, double blind clinical trial provided treatment for 160
cocaine-dependent opioid addicts, aged 18-65 years. Participants were stabilized on LAAM
maintenance during the first 4 weeks and cocaine use was assessed; participants were then
stratified by level of cocaine use and randomly assigned to receive one of the following:
placebo disulfiram (0 mg/day), disulfiram at 62. 5 mg/day, disulfiram at 125 mg/day, or
disulfiram at 250 mg/day. During induction onto LAAM, participants were administered
increasing doses of LAAM plus placebo disulfiram on a thrice-weekly basis until maintenance
doses of LAAM are attained. At the beginning of week 5, participants received LAAM plus
disulfiram or placebo disulfiram according to their randomized assignments, and were
maintained on these agents through week 16. At the end of the study, participants underwent
detoxification from LAAM and active/placebo medication over a 4- to 6-week period. All
participants received weekly 1-hour psychotherapy (Cognitive Behavioral Treatment) with
experienced clinicians specifically trained to deliver the therapy and who received ongoing
supervision. The primary outcomes were retention and reduction in opioid and cocaine use, as
assessed by self-report and confirmed by thrice-weekly urinalyses. Secondary outcomes
included reductions in other illicit drug and alcohol use, as well as improvements in
psychosocial functioning.
Disulfiram in Metastatic Melanoma [Completed]
Melanoma remains a malignancy that is largely resistant to chemotherapy. Metastatic disease
responds poorly to the treatments used today with only 2 out of 30 drugs tested, DTIC and
nitrosoureas, showing response rates greater than 10%, and complete responses are rare.
DTIC-based regimen has been recognized as a standard chemotherapy for advanced melanoma, and
temozolomide demonstrated efficacy equal to that of DTIC and is an oral alternative agent
that also crosses the blood brain barrier. Randomized phase III trials have shown no
survival benefit of adding other agents (cisplatin, BCNU, and tamoxifen). Biochemotherapy is
being developed extensively with moderate improvement in the responsive rate (approximately
50%) and is under evaluation in randomized trial to identify whether there is survival
benefit to this strategy, compared with chemotherapy alone. Recently, a randomized phase III
study comparing chemotherapy (cisplatin, dacarbazine, and tamoxifen) with biochemotherapy
(the same chemotherapy regimen plus high-dose IL-2 and interferon alfa) have shown 44%
response rate for biochemotherapy vs. 27% for chemotherapy. However, the tendency toward an
increased response rate in patients who received biochemotherapy did not translate into an
increase in overall survival, and there was, in fact, a trend for a survival advantage in
patients receiving chemotherapy alone (median survival: 10. 7 vs 15. 8 months). New agents (or
combinations) need to be developed for this refractory malignancy.
Disulfiram (DSF), an agent used to treat alcoholism for the past few decades, has been shown
to induce apoptosis in thymocytes. The hypothetical mechanism is that DSF chelates copper and
creates an intracellular oxidative stress by oxidizing glutathione and establishing a
recycling situation.
It has been demonstrated that redox regulations in melanoma cells are aberrant and metal
chelators (such as dithiocarbamate) alter the redox status and induce apoptosis in melanoma
cells. We have recently explored the effect of disulfiram (DSF), a member of the
dithiocarbamate family, on apoptosis in melanoma cells and as we anticipated, DSF caused a 3
to 5-fold increase in apoptosis in all three melanoma cell strains being tested at a very low
dose (25-50ng/ml). The same dose of DSF did not have significant apoptotic effect on
melanocytes. We are currently studying the mechanisms by which DSF induces apoptosis in
melanoma cells.
The advantages of using DSF in this phase I/II trial are the following:
DSF has been used as a drug for many years for the treatment of alcoholism. It's mechanism,
pharmacokinetics, toxicity/tolerable dose are well known, and this drug is relatively
non-toxic by itself at therapeutic dose. Doses of greater than 3000mg/m2 can cause reversible
confusion.
Acute overdose in the absence of ethanol is an infrequent event. It rarely occurs in
children, or adult for suicidal purpose. Combined toxicity (with metronidazole or
isoniazid), or unmasking of underlying psychoses in patients stressed by the withdrawal of
alcohol may occur.
Adults may have clinical signs after acute ingestion of about 3 grams of DSF, and death may
occur with ingestion of 10 to 30 grams. Brewer (1993) reported a case of an adult who
ingested 600 mg daily for over 6 years and experienced no significant side effects other than
slight drowsiness. Single doses of up to 6 grams/day have been reported in adults without
adverse effect. A phase I study using combination of disulfiram with cisplatin was reported
by Stewart DJ et al in 1987. The dose of DSF ranged from 1000 mg/m2 to 3000 mg/m2 (PO), and
reversible confusion was the dose-limiting toxicity at a disulfiram dose of 3000 mg/m2
administered 1 hr before the end of a 2-hr cisplatin infusion. A randomized phase II study
of cisplatin alone (100 mg/m2) versus cisplatin plus disulfiram (2000 mg/m2, PO) have shown
enhancing gastrointestinal and ototoxicities (ECOG 2-3), and no difference in nephrotoxicity
between two groups.
Symptoms of overdose commonly involved the CNS system, which include lethargy, drowsiness,
ataxia, movement disorders, psychoses, seizure and coma.
DSF can be taken orally; therefore, it is convenient to administer.
DSF can penetrate the blood-brain barrier (unlike dacarbazine and many other chemotherapy
agents); therefore, it might have an active effect on CNS metastasis.
This study is designed to include women and minorities, but is not designed to measure
differences of intervention effect.
Depot Disulfiram for AIDS and ARC [Completed]
To assess the safety and efficacy of depot disulfiram as a new treatment for AIDS and AIDS
related complex.
Disulfiram for Treating Cocaine Dependence in Individuals Maintained on Methadone [Completed]
Cocaine is an extremely addictive stimulant drug that directly affects the brain. It is used
in several different forms and can be snorted, smoked, or injected to achieve the desired
effect. Cocaine users are at risk for many health problems, both directly and indirectly
related to the effects of cocaine. Disulfiram, a drug used to treat chronic alcoholism, may
be effective in reducing cocaine use. This study will evaluate the effectiveness of three
different doses of disulfiram in treating cocaine dependence in opioid- and cocaine-dependent
individuals maintained on methadone.
Disulfiram Interactions With HIV Medications: Clinical Implications [Recruiting]
The purpose of this study is to determine whether disulfiram might be a safe and effective
treatment for cocaine and/or alcohol dependence in patients with HIV disease. This research
is designed to characterize the presence or absence of significant drug interactions between
disulfiram and HIV medications using standard clinical pharmacology techniques as well as
monitor any side effects that might occur when these medications are administered together.
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