Disulfiram for Cocaine Use Disorder
Disulfiram (250 mg daily) is an effective pharmacotherapy for cocaine dependence, reducing both the frequency and quantity of cocaine use, particularly when combined with cognitive behavioral therapy. 1, 2
Evidence for Efficacy
Disulfiram demonstrates consistent benefit across multiple high-quality randomized controlled trials:
In methadone-maintained patients, disulfiram significantly decreased both the quantity and frequency of cocaine use compared to placebo, even in patients without comorbid alcohol abuse. 3
In general cocaine-dependent populations, disulfiram reduced cocaine use significantly more than placebo (p<0.01), with benefits most pronounced in patients who abstained from alcohol during treatment. 1
In buprenorphine-treated patients, disulfiram participants reported significantly less frequent cocaine use compared to placebo. 2
Mechanism of Action
Disulfiram works through inhibition of dopamine β-hydroxylase (DβH), which converts dopamine to norepinephrine. 3, 4 This results in:
- Excess dopamine accumulation 3
- Decreased norepinephrine synthesis 3
- Potential blunting of cocaine craving or alteration of the cocaine "high" 3
Optimal Treatment Protocol
Dosing: 250 mg daily, administered for at least 12 weeks. 1, 2
Combination therapy: Disulfiram should be paired with cognitive behavioral therapy (CBT) rather than interpersonal psychotherapy, as CBT significantly enhances cocaine use reduction (p<0.01). 1
Monitoring compliance: Use riboflavin marker procedures or directly observed therapy (such as placing medication in methadone doses) to ensure adherence. 3, 1
Pharmacogenetic Considerations
Response to disulfiram varies by DBH genotype:
CC-homozygous patients (normal DβH levels) show robust response, with cocaine-positive urines dropping from 84% to 56% (p=0.0001). 5
T-allele carriers (genetically low DβH) show minimal to no response to disulfiram. 2, 5
If genetic testing is available, disulfiram is most appropriate for CC-homozygous individuals. 5
Safety Profile
Adverse effects are mild and not considerably different from placebo. 1 However, critical contraindications exist:
Avoid in acute cocaine intoxication: Never use disulfiram during acute cocaine intoxication when cardiovascular complications are present, as management requires benzodiazepines and vasodilators, not disulfiram. 6
Alcohol abstinence: Benefits are greatest when patients fully abstain from alcohol during treatment. 1
Clinical Implementation
Patient selection: Disulfiram is appropriate for:
- Cocaine-dependent patients in methadone or buprenorphine maintenance programs 3, 2
- General cocaine-dependent outpatients 1
- Patients with or without comorbid alcohol abuse 3, 1
Duration: Minimum 12-week treatment course, with monitoring of cocaine use through weekly urine toxicology screens. 3, 1
Concurrent medications: Safe to use with methadone or buprenorphine maintenance therapy. 3, 2
Common Pitfalls to Avoid
Do not rely on disulfiram's alcohol deterrent effect as the primary mechanism for cocaine reduction—it exerts direct effects on cocaine use independent of alcohol consumption. 1
Do not use disulfiram as monotherapy—always combine with structured behavioral therapy, preferably CBT. 1
Do not administer during acute cocaine intoxication with cardiovascular symptoms—use benzodiazepines and nitroglycerin or calcium channel blockers instead. 6