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Center for Substance Abuse Treatment. Incorporating Alcohol Pharmacotherapies Into Medical Practice. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2009. (Treatment Improvement Protocol (TIP) Series, No. 49.)

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Incorporating Alcohol Pharmacotherapies Into Medical Practice.

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Chapter 3—Disulfiram

Disulfiram At a Glance

Chemical name: Bis(diethylthiocarbamoyl) disulfide.

Trade name: Antabuse®.

U.S. distributor: Odyssey Pharmaceuticals, Inc., East Hanover, NJ.

U.S. Food and Drug Administration approval to treat alcohol dependence: 1951.

Dosage/How taken: Tablet by mouth once daily (also may be crushed and mixed with water, coffee, tea, milk, soft drink, or fruit juice).

How supplied: Bottles of 100 or 1,000 250 mg tablets or bottles of 50, 100, or 500 500 mg tablets.

Storage: Keep out of reach of children; keep tightly closed in original container; store at room temperature, away from excess heat and moisture (not in the bathroom or near a sink); discard when outdated or no longer needed.

What Is Disulfiram?

Disulfiram was the first medication approved by the U.S. Food and Drug Administration (FDA) to treat chronic alcohol dependence. In its pure state, disulfiram is a white to off-white, odorless, almost tasteless powder, which is soluble in water and alcohol. Disulfiram, an alcohol-aversive or alcohol-sensitizing agent, causes an acutely toxic physical reaction when mixed with alcohol. Continuing research and clinical findings have clarified disulfiram's mode of action and established its safe and effective use in the treatment of alcohol use disorders (AUDs) in some patient groups.

Brief History of Development

Exhibit 3-1 summarizes disulfiram's development history.

Exhibit 3-1 Brief History of Disulfiram Development

DatesEvents
1930sDisulfiram's alcohol-aversive effects are first observed when workers in the vulcanized rubber industry, exposed to tetraethylthiuram disulfide, become ill after drinking alcohol.
1947In Copenhagen, researchers studying compounds to treat parasitic stomach infections take a small dose of disulfiram to check its side effects. Later they become ill after an alcoholic drink. They conclude that an interaction of disulfiram and alcohol is responsible and conduct a study to confirm their findings (Hald & Jacobsen, 1948).
Late 1940s, early 1950sThe Danish group performs additional studies of disulfiram treatment for alcohol dependence. Basing its initial paradigm on aversion conditioning, it administers high disulfiram doses (e.g., 1,000 to 3,000 mg daily) to maximize patient reactions.

FDA approves disulfiram to treat alcohol dependence in the United States.

Wyeth-Ayerst Laboratories begins manufacturing Antabuse® tablets (now manufactured by PLIVA and distributed in the United States by Odyssey Pharmaceuticals).

Ruth Fox, M.D., the founding president of the American Society of Addiction Medicine, is the first American to use disulfiram to treat alcohol dependence, starting in 1949. When her patients report serious side effects, Fox reduces the dosage and counsels them on the severe reactions that could result from drinking alcohol. She concludes that disulfiram is effective in deterring drinking in patients with alcohol dependence and treats about 2,500 patients with disulfiram.
Late 1950s to the presentAfter reports of severe reactions, including some deaths, therapeutic emphasis shifts from using disulfiram for aversion conditioning to using it to support abstinence. This entails using lower dosages to control disulfiram toxicity, excluding patients with myocardial infarction or cirrhosis of the liver, and combining the medication with other types of support.

Pharmacology

Aversive treatment

Unlike other medications approved to treat alcohol dependence, disulfiram does not affect brain opiate, γ-aminobutyric acid, or glutamate receptors directly. However, it does have some central nervous system effects, inhibiting enzyme dopamine β-hydroxylase and affecting serotonergic function. Whether disulfiram directly decreases the urge to drink remains uncertain. However, disulfiram definitely disrupts the metabolism of alcohol, causing a severe reaction when patients mix disulfiram and alcohol. Patient knowledge of a possible severe reaction to alcohol consumption is thought to increase the patient's motivation to remain abstinent. Some experts (e.g., Schuckit, 2006) question disulfiram's effectiveness because the time between alcohol ingestion and the reaction can be as long as 30 minutes and the intensity of the reaction is unpredictable.

Effect on oxidation of alcohol

Normally, the enzyme alcohol dehydrogenase in the liver and brain transforms alcohol into acetaldehyde. The enzyme aldehyde dehydrogenase (ALDH), also in the liver and brain, oxidizes the acetaldehyde byproduct into acetic acid. Disulfiram blocks this oxidation by inhibiting ALDH, causing a rapid rise of acetaldehyde in the blood when alcohol is consumed. The result is called a disulfiram-alcohol reaction, and it may increase the acetaldehyde concentration in blood to 5 to 10 times that occurring without disulfiram. Disulfiram does not appear to affect the rate of alcohol elimination from the body.

The disulfiram-alcohol reaction

The disulfiram-alcohol reaction usually begins about 10 to 30 minutes after alcohol is ingested. Its adverse effects range from moderate to severe (Exhibit 3-2). Intensity varies with individual patient characteristics. The reaction is generally proportional to the amounts of disulfiram and alcohol ingested. Mild effects may occur at blood alcohol concentrations of 5 to 10 mg/100 mL. At 50 mg/100 mL, effects usually are fully developed. When the concentration reaches 125 to 150 mg/100 mL, unconsciousness may occur. Although disulfiram-alcohol reactions can be life threatening, as indicated in Exhibit 3-2, the reduced dosages and careful patient medical screening now in practice have made this outcome extremely rare.

Exhibit 3-2 Possible Effects of the Disulfiram-Alcohol Reaction

Body Part AffectedModerateSevere
Body skinSweating
Warmth and flushing, particularly on upper chest and face
None
Respiratory systemHyperventilation
Respiratory difficulty/dyspnea
Respiratory depression
Head, neck, throatAcetaldehyde breath odor
Blurred vision
Head and neck throbbing
Thirst
None
Stomach, digestive systemNausea/vomitingNone
Chest, heart, circulatory systemChest pain/palpitations
Hypotension
Tachycardia
Cardiovascular collapse
Arrhythmia
Myocardial infarction (in individuals with preexisting coronary artery disease)
Acute congestive heart failure (in individuals with preexisting myocardial dysfunction)
Brain/ nervous systemVertigo
Syncope
Marked uneasiness
Confusion
Seizures
Unconsciousness
OtherWeaknessDeath

Early researchers believed that patients needed to experience at least one supervised disulfiram-alcohol reaction to understand its effects. The practice of deliberately inducing a reaction by giving large doses of disulfiram in conjunction with “alcohol challenges” has been abandoned. A clear, convincing description of the reaction is considered sufficient for most patients.

Disulfiram absorption and elimination

About 80 to 95 percent of ingested disulfiram is absorbed from the gastrointestinal tract and rapidly distributed to tissues and organs. It is then metabolized to various mixed disulfides. The unabsorbed fraction is excreted. Disulfiram is irreversibly bound to ALDH. It can take up to 2 weeks for the body to synthesize sufficient unbound enzyme to metabolize alcohol adequately. This is why alcohol ingestion may produce unpleasant symptoms for up to 2 weeks after a patient has taken the last dose of disulfiram.

Why Use Disulfiram?

Disulfiram may work as an adjunct to psychosocial treatment to eliminate alcohol consumption for patients who can achieve initial abstinence of at least 12 hours, are committed to maintaining abstinence, agree to take the medication, and do not have contraindications to disulfiram.

Efficacy

Findings on the efficacy of disulfiram treatment are mixed. (To review some reports, see the online annotated bibliography and literature review at http://www.kap.samhsa.gov.)

Positive findings

Studies concluding that disulfiram is effective in treating AUDs frequently emphasize the circumstances in which it is administered to patients. In particular, the level and quality of supervision a patient receives while taking disulfiram are believed to be important elements in its success (e.g., Brewer, Meyers, & Johnsen, 2000; Kristenson, 1995). Some studies have found that court-ordered disulfiram therapy promotes efficacy by increasing adherence to the disulfiram regimen (Martin, Clapp, Alfers, & Beresford, 2004; Martin, Mangum, & Beresford, 2005). Use of incentives, contracting with the patient and a significant other to ensure adherence, providing regular reminders to the patient, and patient behavioral training and social support also may enhance disulfiram efficacy by increasing treatment adherence.

Most experts (e.g., Schuckit, 2006) agree that an optimum disulfiram response requires its use in a specialty substance abuse treatment program. One study suggests that disulfiram might be more effective in promoting short-term abstinence and treatment retention after detoxification than in preventing long-term relapse (e.g., Chandrasekaran, Sivaprakash, & Chitraleka, 2001). Nevertheless, the most rigorous study of disulfiram therapy (Fuller et al., 1986) showed unequivocally that disulfiram (250 mg/day), compared with placebo (1 mg/day) or a vitamin, reduced the proportion of days of alcohol consumption for the duration of the study (1 year) in male veterans who reported some drinking. However, there were no differences between treatment groups in the percentage of veterans sustaining abstinence throughout the study period.

Negative findings

Some experts dismiss disulfiram as a viable treatment option, particularly in primary care settings. This conclusion is based on mixed results with disulfiram in clinical trials and the severe adverse effects that may result from the disulfiram-alcohol reaction, as well as concerns about other potentially serious side effects and “problems with compliance” (Williams, 2005, pp. 1776–1777). The capacity to arrange ongoing supervision of disulfiram ingestion may be limited in a primary care setting.

Appropriate patients

The consensus panel concludes that disulfiram is most effective for patients who have undergone detoxification or are in the initiation stage of abstinence, especially when they are committed to abstinence and receive adequate, ongoing supervision. Disulfiram may not reduce the urge to drink alcohol. However, it may assist in motivating the patient not to drink. As with other medications, general efficacy also increases when disulfiram is administered in conjunction with intensive behavioral interventions.

Patients with severely impaired judgment or who are highly impulsive from a severe mental illness or cognitive impairment may be inappropriate candidates for treatment with disulfiram.

Safety

Disulfiram has been used to treat AUDs for almost 60 years. Deaths from the disulfiram-alcohol reaction have become rare because lower dosages are used and patients with severe cardiac disease are excluded from disulfiram treatment (Chick, 1999). Its hepatotoxicity in some patients remains a concern (see Side Effects, Contraindications, and Cautions below).

Side effects of disulfiram are usually minor (see Exhibit 3-4 below). Severe adverse reactions are uncommon (see Exhibit 3-8 below). However, patients receiving disulfiram should be monitored for hepatotoxicity (see Timing of Laboratory Work below). Disulfiram may cause hepatitis, but the risk is low. Estimates of disulfiram-induced hepatitis are between 1 in 25,000 (Wright, Vafier, & Lake, 1988) and 1 in 30,000 (Chick, 1999, p. 427) patients treated per year. A disproportionate number of these cases may be associated with use of disulfiram to treat nickel allergy (an unusual but known indication for use of disulfiram).

A black-box warning about treatment with disulfiram is included in the Antabuse package insert. Before administering disulfiram, the clinician should inform patients and their families about the disulfiram-alcohol reaction, including that this reaction may occur for up to 14 days between the last ingested dose of disulfiram and alcohol consumption.

Disulfiram Black-Box Warning

Disulfiram should never be administered to a patient who is in a state of alcohol intoxication or without the patient's full knowledge. The physician should instruct relatives accordingly.

How Is Disulfiram Used?

Before Initiating Treatment With Disulfiram

Physicians should not administer disulfiram until the following steps have been taken:

  • Educate the patient about disulfiram and obtain informed consent.
  • Wait until the patient has abstained from alcohol at least 12 hours and/or breath or blood alcohol level is zero.
  • Perform a physical exam, baseline liver and kidney function tests, and a pregnancy test for women. Perform an electrocardiogram if clinically indicated (e.g., history of heart disease).
  • Complete a medical and psychiatric history. Determine allergies to disulfiram or other drugs; prescription and nonprescription medications taken, including vitamins; history of cardiovascular disease, diabetes, thyroid disease, seizure disorder, central nervous system impairment, or kidney or liver disease; and for women, reproductive status, including current pregnancy or plans to become pregnant or to breast-feed.

Supervised Ingestion

There is strong evidence that supervised ingestion is necessary for disulfiram therapy compliance (e.g., Brewer et al., 2000; Kristenson, 1995; reviewed by Fuller & Gordis, 2004). Although not absolutely essential, supervised administration by a pharmacist, healthcare provider, or family member is preferred as a key component of the treatment plan.

Dosage

Exhibit 3-3 summarizes standard dosage information for disulfiram.

Exhibit 3-3 Disulfiram Dosages

Initial dosage250 mg/day in 1 morning or evening dose for 1–2 weeks
Average maintenance dosage250 mg/day
Dosage range125–500 mg/day
Maximum dosage500 mg/day

Additional dosage information includes the following:

  • Instruct patients who experience sedation with disulfiram to take it at bedtime. If daytime sedation persists, adjust the dosage downward.
  • If a patient can drink alcohol without problems when compliant with the routine starting dose (which is rare), increase the dosage (dosage may be increased up to 500 mg/day with careful monitoring). Never exceed 500 mg/day.
  • Instruct patients who miss a dose to take it as soon as they remember. However, if it is almost time for the next dose, they should skip the missed dose.
  • Tell patients never to take a double dose of disulfiram.

Side Effects, Contraindications, and Cautions

Disulfiram can cause minor side effects (Exhibit 3-4). The common side effects typically occur during the first 2 weeks of therapy and wane either spontaneously or after a decrease in the disulfiram dosage.

Exhibit 3-4 Disulfiram Side Effects

Skin/acneiform eruptions*
Allergic dermatitis*
Mild drowsiness
Fatigue
Headache
Impotence
Metallic or garliclike aftertaste
*

Dermatologic side effects often can be managed with concomitant antihistamines.

Hepatic toxicity including hepatic failure resulting in transplantation or death has been reported. Severe and sometimes fatal hepatitis associated with disulfiram therapy may develop even after many months of therapy. Hepatic toxicity has occurred in patients with or without a history of abnormal liver function.

Patients should be instructed to call their physician immediately if they develop symptoms of possible hepatic impairment (Exhibit 3-5).

Exhibit 3-5 Symptoms of Disulfiram-Induced Hepatic Impairment

Excessive tiredness
Weakness
Lack of energy
Loss of appetite
Upset stomach
Vomiting
Yellowness of the skin/eyes
Dark urine
Fever
Light-colored stools

Exhibit 3-6 summarizes contraindications for disulfiram therapy, and Exhibit 3-7 summarizes cautions.

Exhibit 3-6 Disulfiram Contraindications

Patient Condition or CircumstanceTreatment Recommendation
Known hypersensitivity to disulfiram or other thiuram derivatives used in pesticides and rubber vulcanization; sulfur or nickel allergyDo not administer disulfiram.
PsychosisDisulfiram is relatively contraindicated in patients with decompensated psychoses but can be used with caution in treated, stable patients with schizophrenia or other psychotic disorders.
Severe myocardial disease and/or coronary occlusionDisulfiram is relatively contraindicated in patients with severe myocardial disease or coronary occlusion, with clinical risk of disulfiram therapy balanced against clinical risk of ongoing alcohol abuse. Perform an electrocardiogram before and during disulfiram therapy and follow closely.
Pregnant or nursing womenAlthough disulfiram is not absolutely contraindicated, it should be avoided because risk to the fetus is unknown. (Pregnant patients should receive behavioral treatment, on an inpatient basis if necessary.) Do not give disulfiram to nursing mothers. Patients should discontinue nursing before taking disulfiram.

Exhibit 3-7 Disulfiram Cautions

Patient Condition or CircumstanceTreatment Recommendation
History of cardiac disease, diabetes mellitus, hypothyroidism, epilepsy, cerebral damage, chronic or acute nephritis, hepatic cirrhosis, or hepatic insufficiencyUse with caution. No evidence exists that patients with preexisting liver disease are more likely to suffer severe hepatotoxicity from disulfiram therapy.
Patients with hepatitis CAccording to current available evidence, if baseline transaminase levels are normal or only moderately elevated (less than five times the upper limit of normal), use with careful monitoring of liver function.
Children and adolescentsSafety and efficacy for children has not been determined. One study indicates that disulfiram can be safe and effective with adolescents (Niederhofer & Staffen, 2003). Administer with caution.
Patients receiving or who have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations (e.g., cough syrups, tonics); also patients exposed to ethylene dibromide or its vapors (e.g., in paint, paint thinner, varnish, shellac)Do not use disulfiram until substances are out of the patient's system.
Patients using products that contain alcohol in disguised forms (e.g., vinegars, sauces, aftershave lotions, liniments)Instruct patients to test any alcohol-containing product before using it by applying some to a small area of the skin for 1 to 2 hours. If there is no redness, itching, or unwanted effects, the product may be used safely.
Age 61 or olderDosages may need to be decreased.

Patient Management

Exhibit 3-8 lists severe adverse reactions that may occur with disulfiram and ways to manage them. These reactions are uncommon.

Exhibit 3-8 Adverse Reactions to Disulfiram and Their Management

Adverse ReactionManagement
Optic neuritisUsually diagnosed after patient complains of visual disturbance. Discontinue disulfiram and conduct an ophthalmologic examination.
Peripheral neuritis, polyneuritis, peripheral neuropathyUsually diagnosed after patient complains of paresthesias (numbness or tingling). Discontinue disulfiram and observe patient or arrange for neurological evaluation.
Hepatitis, including cholestatic and fulminant hepatitis, as well as hepatic failure*When symptoms of hepatic dysfunction are reported or observed (see Exhibit 3-5), perform a medical history and physical examination and obtain followup liver function tests. When clinical or laboratory evidence of hepatic dysfunction is found, discontinue disulfiram immediately. Maintain clinical monitoring of symptoms and liver function. Follow findings to resolution.
PsychosisPsychotic reactions to disulfiram have been noted, usually attributable to high disulfiram dosage associated with toxicity to other drugs (e.g., metronidazole, isoniazid) or the unmasking of underlying psychoses in patients stressed by alcohol withdrawal. When psychosis is diagnosed and other interacting drugs are present, reduce or discontinue disulfiram and treat underlying psychoses as indicated.
*

Serious disulfiram-induced hepatic injury occurs rarely, and the precise etiology is unknown.

Drug interactions with disulfiram and their management

Exhibit 3-9 describes the most common drug interactions with disulfiram and their clinical management.

Exhibit 3-9 Drug Interactions With Disulfiram

DrugEffect With DisulfiramRecommended Action
Benzodiazepines
Chlordiazepoxide (Librium®)
Diazepam (Valium®)
Decreases plasma clearance of chlordiazepoxide or diazepamSubstitute oxazepam (Serax®) or lorazepam (Ativan®)
IsoniazidMay cause unsteady gait, changes in mental stateDiscontinue disulfiram if either effect is noted
Rifampin (Rifadin®, Rimactane®)If used with isoniazid to treat tuberculosis, see isoniazid effects aboveAdjust dosages as needed
Metronidazole (Flagyl®)Leads to a greater likelihood of confusion or psychosisDo not prescribe disulfiram and metronidazole concomitantly
Oral anticoagulant (e.g., warfarin [Coumadin®])Inhibits warfarin metabolismAdjust dosages as needed
Oral hypoglycemicProduces disulfiram-like reactions with alcoholMonitor carefully if prescribing oral hypoglycemics and disulfiram concomitantly
Phenytoin (Dilantin®)Increases serum levels through CYP 450 2C9 inhibitionObtain baseline phenytoin serum level before disulfiram therapy; reevaluate level during therapy; adjust dosage if phenytoin level increases
TheophyllineIncreases serum levels through CYP 450 1A2 inhibitionObtain baseline theophylline serum level before disulfiram therapy; reevaluate level during therapy; adjust dosage if theophylline serum level increases
Tricyclic antidepressants, amitriptyline (Elavil®)May cause delirium with concurrent administrationAdjust dosages, discontinue disulfiram, or switch to another class of antidepressant medication
Desipramine (Norpramin®), imipramine (Tofranil®)Decreases total body clearance and increases elimination half-life and peak plasma levels of desipramine or imipramineMonitor closely; adjust dosages if needed

Timing of laboratory work

Exhibit 3-10 summarizes the recommended laboratory testing regimen for disulfiram therapy. In general, liver function requires ongoing monitoring because of disulfiram's occasional association with hepatic injury. In contrast to liver injury caused by alcohol, which typically shows a high aspartate aminotransferase-to-alanine aminotransferase ratio, disulfiram liver injury usually shows equivalent and very high elevations of both enzymes (Bjornsson, Nordlinder, & Olsson, 2006). Pregnant women should discontinue taking disulfiram immediately. Urine toxicology screening is not an ideal method of detecting alcohol use, although it sometimes can detect use that occurred within a few hours of test administration.

Exhibit 3-10 Laboratory Testing in Disulfiram Therapy

Interval/PeriodType of Test
Before starting disulfiram therapy to confirm abstinence and determine baselines after stabilizationBreath or blood alcohol tests (if clinically indicated to confirm abstinence)
Liver function tests: Alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin, total protein, albumin, prothrombin time
Complete blood count, routine chemistries (if clinically indicated)
Kidney function tests: Routine blood urea nitrogen (BUN), creatinine
Pregnancy test (women of childbearing age)
10–14 days after initiation of therapy and then monthly (or more frequently) for first 6 months of therapy; every 3 months thereafterLiver function tests: Alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, bilirubin
Monthly during therapyPregnancy test (women of childbearing age)
As clinically indicated during therapyKidney function tests: BUN, creatinine
Urine toxicology screen: Perform only when concern exists about unreported alcohol or drug use

Disulfiram overdose and its management

Severe cases of disulfiram poisoning have been reported, mainly in children who have ingested large amounts because of patients' negligent handling or storage of their medication. Symptoms of overdose include drowsiness followed by coma or persistent nausea, vomiting, aggressive or psychotic behavior, and ascending flaccid paralysis that can reach the cranial nerves. Treatment consists of administration of oxygen therapy, glucose (5 percent intravenously), and sodium ascorbate (1 gram intravenously). The patient should be kept in bed and as quiet as possible with appropriate symptomatic treatment.

Addressing reported drinking

Patients seemingly on an adequate maintenance dosage of disulfiram who report that they can drink with impunity could be disposing of their tablets without taking them. Physicians should not conclude that disulfiram is ineffective until patients are proved to have been taking their daily tablets. Once patient adherence is confirmed, the physician should consider increasing the disulfiram dosage (see Exhibit 3-3) or changing the patient to another medication.

Genetic factors may influence sensitivity to disulfiram in some patients (reviewed by Kenna, McGeary, & Swift, 2004a, 2004b). Wide individual differences exist in the activity of the target enzyme ALDH. Individuals with low intrinsic ALDH activity are more likely to exhibit high sensitivity to disulfiram, and those with high intrinsic ALDH are more likely to show little or no sensitivity to disulfiram.

Managing a disulfiram-alcohol reaction

The duration of the disulfiram-alcohol reaction varies from 30 to 60 minutes in mild cases to several hours or until the alcohol is metabolized in more severe cases. When effects are severe, supportive measures may be needed to restore blood pressure and treat shock. Administration of oxygen or carbogen (95 percent oxygen, 5 percent carbon dioxide), large intravenous doses of vitamin C (1 g), ephedrine sulfate, or intravenous antihistamines may be indicated. Potassium levels should be monitored particularly in patients on digitalis because hypokalemia has been reported.

Patient Education

Patients should receive thorough education about disulfiram. Use of disulfiram should include ongoing monitoring, medical management, and counseling. Used without proper patient education, motivation, and supportive intervention, disulfiram is unlikely to have more than a brief effect on drinking patterns, particularly in patients with poor medication compliance, more severe forms of alcohol dependence, or both.

In addition to giving patients the general patient education discussed in Chapter 6, healthcare providers should educate patients about the following key points regarding disulfiram therapy:

  • Benefits and limitations of disulfiram
  • What to expect from disulfiram and normal time to full effect
  • Complete information about the disulfiram-alcohol reaction
  • Strong cautions about surreptitious drinking while on disulfiram
  • Warnings about using alcohol in disguised forms, such as in sauces, vinegars, cough mixtures, aftershave lotions, or liniments
  • Importance of continued counseling and 12-Step or mutual-help group participation during disulfiram therapy
  • Importance of informing the counselor and prescribing professional if a slip or relapse occurs
  • Importance of telling physicians or dentists that the patient is taking disulfiram when he or she is scheduled for surgery, including dental surgery
  • Importance of carrying a safety identification card indicating that the patient is taking disulfiram, symptoms of possible disulfiram-alcohol reactions, and the physician or institution to contact in an emergency
  • Symptoms of potential neurologic injury to report immediately to the physician
  • Symptoms of potential liver injury to report immediately to the physician.

Clinicians are advised to document that a patient has received and understands the information described above and to obtain the patient's informed written consent to treatment before prescribing disulfiram.

Who Is Appropriate for Treatment With Disulfiram?

  • Patients motivated for treatment and committed to total abstinence
  • Patients capable of understanding the consequences of drinking alcohol while taking disulfiram
  • Medically appropriate patients
  • Patients who can receive supervised dosing
  • Patients who are abstinent from alcohol
  • Patients who maintain abstinence during treatment
  • Patients who are codependent on or also abuse cocaine.

Treatment Duration and Discontinuing Disulfiram

Prolonged disulfiram administration does not produce tolerance. Daily, uninterrupted dosing may be continued until the patient has established stable, long-term alcohol abstinence. Depending on the patient, disulfiram therapy may continue for months or years. A 9-year study of 180 patients with chronic alcohol dependence (Krampe et al., 2006) concluded that the beneficial action of long-term (12- to 20-month) supervised disulfiram therapy was psychological, not pharmacological, because placebo worked as well as disulfiram. Nevertheless, the study found that the likelihood that a patient would remain continuously abstinent years after termination of medication therapy was directly related to the length of time the patient continued supervised therapy with either disulfiram or placebo.

For some patients who have completed successful treatment with disulfiram and who are facing anticipated high-risk relapse situations such as social events or travel, it may be appropriate to restart disulfiram along with behavioral interventions to help them cope with the high-risk situation and avoid relapse.

No withdrawal syndrome is associated with discontinuing disulfiram, but patients must be warned that disulfiram-alcohol reactions may occur within 2 weeks of discontinuing the medication.

Final Clinical Thoughts

Disulfiram appears to have modest clinical efficacy in maintaining alcohol abstinence in patients with AUDs, particularly when administered under supervision. Patients who are motivated for treatment, commit to abstinence, have supervised dose administration, and understand and participate in their treatment appear to derive the greatest benefits from disulfiram therapy. However, disulfiram does not appear to produce overall higher abstinence rates than placebo. Disulfiram therapy also has rare but serious risks of neurologic and hepatic toxicity. Patients require careful clinical and laboratory monitoring during disulfiram therapy. Disulfiram can be considered for any patient who is alcohol dependent, does not display contraindications, has a goal of total abstinence, and can comply with appropriate monitoring.

Clinical visits in which the practitioner and patient discuss the risks and benefits of disulfiram therapy can motivate the patient to commit to alcohol abstinence. In addition to the pharmacologic actions of the medication, the patient's simply deciding to take the medication can enhance motivation for abstinence. The risks associated with disulfiram are well known and serious. However, patients can benefit from disulfiram as long as they receive careful clinical and laboratory monitoring to manage the risks associated with this therapy.

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