Medical complications arising from an ethanol-disulfiram reaction can include tachycardia, hypotension, and electrocardiographic changes. Fatalities have been reported due to myocardial infarction or cerebrovascular accident.5 As a result, people with a history of severe myocardial disease should generally not be prescribed disulfiram.
Side effects from disulfiram itself include drowsiness, impotence, headache, acne, and a metallic or garlic-like aftertaste. Toxicity can also lead to psychiatric reactions such as increased depression and psychosis, possibly because of the inhibition of dopamine β–hydroxylase.5
Hepatic and neurological reactions are the most commonly reported toxic reactions.19 Disulfiram-induced hepatitis usually occurs within 2 months of initiation of treatment, but may occur up to 6 months after starting disulfiram.20 This form of liver toxicity is believed to be an allergic or hypersensitivity reaction and can lead to hepatic necrosis and death due to liver failure. Some clinicians recommend obtaining liver function tests at regular intervals (e.g., at baseline, 2 weeks, 4 weeks, then monthly for 6 months), although the optimal frequency of testing after week 2 is not well established.
Neurological reactions make up approximately 20% of the overall reported side effects from disulfiram, with the most frequent diagnosis being polyneuropathy. Other important reported adverse neurological effects include optic and peripheral neuritis.19
Disulfiram interacts with a number of medications, primarily by slowing down their metabolism and thus increasing risk of toxicity. These drugs include phenytoin, theophylline, anticoagulant drugs, isoniazid, and amitriptyline.19 Prior to starting treatment with disulfiram, phenytoin serum levels should be obtained and monitored throughout treatment. Dosage of oral anticoagulant drugs such as warfarin should also be monitored carefully.
Naltrexone The most common side effect is nausea, which typically occurs in the first week of treatment. In the largest study of naltrexone published to date, approximately 10% of naltrexone-treated subjects reported this side effect.16 Other side effects include headache, anxiety, dizziness, fatigue, vomiting, and insomnia.16
Elevated liver enzymes have been reported with use,17 so liver function should be monitored in patients receiving this medication.
It is unclear how often liver function tests should be performed. One text18 recommends baseline assessment of liver function, monthly monitoring for 3 months, then testing every 2 to 6 months afterwards if results are normal.
Other clinical considerations
Disulfiram Individuals with a history of allergy to thiuram derivatives used in rubber vulcanization or pesticides should not be given disulfiram. Caution should also be used with patients suffering from myocardial disease, diabetes mellitus, cirrhosis, hypothyroidism, seizure disorder, or impaired renal function. Finally, patients should not take disulfiram unless they have abstained from alcohol for at least 12 hours.
Naltrexone Although the recommended dosage of naltrexone for alcohol dependence is 50 mg/d, some patients who experience side effects at that dosage may tolerate 25 mg/d, so starting at this lower dose is often advisable. Some researchers are analyzing the effects of higher dosages (e.g., 100 mg/d) because of evidence that higher blood levels of 6-β-naltrexol might improve treatment outcome.9 The optimal dosage of naltrexone for alcohol dependence is currently not settled, however, and may vary among patients.
Patients should be free of opiates for at least 7 days prior to initiating naltrexone; in the case of methadone, a 10- to 14-day opiate-free interval is prudent. Clinicans should wait approximately 4 days after the patient’s last drink before initiating therapy, since starting naltrexone earlier may lead to more side effects.
Educating patients about both agents
Disulfiram This medication is not to be prescribed lightly; only patients who are fully aware of its potential risks should be taking it. Patients need to be both willing and able to avoid alcohol both in beverage and disguised forms (e.g., alcohol-laced cough syrups).
One useful question to ask patients is, “Can you imagine yourself drinking on disulfiram?” Patients who admit that disulfiram would not deter them from drinking, or who cannot commit to avoiding alcohol in any form, should not use this medication.
Naltrexone Some alcohol-dependent patients are interested in taking naltrexone because they have heard that it may diminish the likelihood of progression from initial drink to full-blown relapse, thus helping them to become controlled drinkers.
Bear in mind that naltrexone does not convert alcohol-dependent individuals into controlled drinkers. Rather, you should tell patients that naltrexone may help them return to abstinence more quickly in the event that they do slip. This statement is consistent with the data about naltrexone and helps to establish and reinforce the goal of abstinence for alcohol-dependent patients.
Which medication for which patient?
When considering which, if either, medication to prescribe for an alcohol-dependent patient, you should initially determine whether contraindications exist. (A rubber allergy would preclude disulfiram, for example.) Then obtain a medical evaluation, including liver function tests, prior to initiating either medication.