Aversion Drug Found for the Treatment of Alcoholism

Researchers accidentally discovered the alcohol deterrent properties of disulfiram (marketed as Antabuse) and recognized its value in the treatment of alcoholism. A person will become violently ill if he or she drinks an alcoholic beverage after taking the substance.

Summary of Event

Alcoholic beverages have been used by humankind since the dawn of history. The drinking of beer, wine, and distilled liquors is an accepted custom in most societies. There is a paradox in this widespread use of alcohol. Families celebrate births and weddings with alcohol, yet many families are destroyed by it. “Demon rum” is condemned by many religious groups, yet, at the same time, wine is often used in religious ceremonies. Antabuse Disulfiram Medications;Antabuse (disulfiram) Alcoholism Drug therapy;alcoholism [kw]Aversion Drug Found for the Treatment of Alcoholism (1948) [kw]Drug Found for the Treatment of Alcoholism, Aversion (1948) [kw]Treatment of Alcoholism, Aversion Drug Found for the (1948) [kw]Alcoholism, Aversion Drug Found for the Treatment of (1948) Antabuse Disulfiram Medications;Antabuse (disulfiram) Alcoholism Drug therapy;alcoholism [g]Europe;1948: Aversion Drug Found for the Treatment of Alcoholism[02210] [g]Denmark;1948: Aversion Drug Found for the Treatment of Alcoholism[02210] [c]Health and medicine;1948: Aversion Drug Found for the Treatment of Alcoholism[02210] Jacobsen, Eric Hald, Jens Fox, Ruth

People drink alcohol for a number of reasons, but a portion of the alcohol-consuming population drink alcohol in such quantities or with such frequency that, sooner or later, they lose control over their lives—with destructive consequences. Alcoholism is a major factor in suicides, automobile fatalities, child abuse, and domestic violence. Chronic consumption of alcohol causes organic disease of the liver, heart, and nervous system. Alcohol abuse is considered to be a top-ranking killer of Americans, ranked closely behind heart disease and cancer. Alcohol is also an insidiously addictive drug. Years of moderate-to-heavy drinking are required before the addiction is manifested.

Over the centuries, societies have tried to curtail the excessive use of alcohol by labeling alcoholics as sinful or weak-willed individuals who have made their own problems and by legal action prohibiting the sale or consumption of alcoholic beverages. Such approaches have failed to protect either the public or susceptible individuals from the misery and destruction of alcohol abuse. Of the U.S. population that is of drinking age, the majority drinks alcoholic beverages to some degree. More than 10 percent of these social drinkers may have serious problems with alcohol and millions more are identified as alcoholics.

The recognition of alcoholism as a disease rather than a moral or legal problem was pioneered by Elvin Morton Jellinek Jellinek, Elvin Morton , an American biometrician who performed extensive epidemiological studies of alcoholism and classified the disease into five types based on dependence of alcohol; pattern of use; and the physiological, psychological, and social consequences of its use. In 1960, Jellinek published The Disease Concept of Alcoholism, Disease Concept of Alcoholism, The (Jellinek) in which alcoholism was presented as a chronic, fatal, progressive disease, and alcohol was identified as the cause of the disease, not a symptom of underlying emotional problems.

The gradual acceptance by the medical community that alcoholism is a disease caused by drinking alcohol supports the beliefs expressed by Alcoholics Anonymous Alcoholics Anonymous (AA), a group founded in 1935 by alcoholics to help other alcoholics stop drinking. Alcoholics Anonymous believes that alcoholics must realize they are powerless over the influence of alcohol. AA maintains that alcoholics can never “recover” and return to a life of social drinking; they must abstain from alcohol for the rest of their lives.

The treatment of alcoholism has long frustrated the medical community because of the limited success in helping the alcoholic abstain from drinking. Since the 1930’s, therapies used to treat alcoholics have included psychological approaches (aversion therapy and psychoanalysis) and the prescription of drugs such as tranquilizers and lithium to help alcoholics overcome their addiction. For a brief period, psychotherapy sessions aided by administration of the powerful hallucinogen lysergic acid diethylamide (LSD) were strongly advocated by some researchers in the late 1960’s as a breakthrough in the treatment of alcoholism. None of these medical approaches has survived or had a lasting impact in the treatment of alcoholism.

In 1951, however, the drug Antabuse was approved by the U.S. Food and Drug Administration (FDA) as an effective agent in the treatment of alcoholism. For the first time, physicians had a specific drug available to help treat alcoholism. The discovery of Antabuse as an effective alcohol deterrent drug was a purely serendipitous event.

In 1947, at the Royal Danish School of Pharmacy in Copenhagen, Eric Jacobsen, a professor of pharmacology, and his assistant Jens Hald were investigating a series of compounds such as anthelmintic agents, potential medicines for treating intestinal parasitic worm infections. The chemical compound disulfiram was selected for further study, and, as was common in those times, the investigators ingested small doses of the chemical for direct observations of potential side effects. No adverse reactions were noted. Several days later, these scientists attended a cocktail party. Shortly after finishing their first drink, both men became violently ill. Because they experienced the same illness at the exact same time, Jacobsen and Hald concluded that a combination of the small dose of disulfiram ingested days earlier and drinking alcoholic beverages had triggered the illness. The concept of using disulfiram as a preventive measure in the treatment of alcoholism became clear. In 1948 in the English medical journal Lancet, Jacobsen and Hald published their preliminary findings supporting the use of the chemical disulfiram in the treatment of alcoholism.

There is some irony in the fact that in 1937, E. E. Williams Williams, E. E. , physician at a rubber plant in Connecticut, wrote a letter to the editor of the Journal of the American Medical Association stating that workers exposed to disulfiram-like compounds, used as rubber polymerization accelerators, could not drink alcohol in any form. After a glass of beer, the workers would experience a flushing of the face and hands, a rapid heartbeat, and their blood pressure would drop twenty points. Williams stated that “men have worked here for years without any complaint other than their inability to drink. . . . One wonders whether one has discovered the cure for alcoholism.”

In reply to Williams’s query, the editor curtly stated that it had long been known that alcohol was a provocative agent that demonstrated the toxicity of such sulfide compounds, including the related chemical carbon disulfide. Although the editor missed Williams’s point about using disulfiram as an alcohol-deterring agent, his statements about the relationship between, and toxicity of, compounds such as carbon disulfide and disulfiram were correct. Twenty years later, it was discovered that in patients who received large doses of disulfiram, significant amounts of the toxic chemical carbon disulfide actually were being produced in the body as a degradation product, or metabolite, of disulfiram.

The body’s marked reaction to the combination of disulfiram and alcohol is a response to disulfiram’s interference with the normal metabolism (detoxification) of ethyl alcohol in the liver. In the absence of disulfiram, enzymes in the liver rapidly metabolize Biochemistry;metabolism or convert ethyl alcohol into acetaldehyde. Acetaldehyde is further converted into the compound acetate, the final nontoxic by-product of ethyl alcohol, by the liver enzyme aldehyde dehydrogenase. Disulfiram is a potent inhibitor of the liver enzyme aldehyde dehydrogenase. Inhibition of this enzyme by disulfiram breaks the chain of reactions necessary to detoxify ethyl alcohol, resulting in a rapid five- to tenfold increase in blood levels of acetaldehyde.

A person who has been taking disulfiram and then consumes alcohol will experience what is known as a disulfiram-ethanol reaction (DER) within minutes. This profoundly unpleasant illness is characterized by the face becoming hot and scarlet, an intense throbbing in the head and neck, and a severe headache. The person may experience difficulty in breathing, chest pain, vomiting, confusion, and blurred vision. The facial flushing is replaced later by a blanched pallor, and blood pressure may fall severely. Symptoms of the DER may last from thirty minutes to several hours, depending on the individual and amount of alcohol consumed. The victim becomes exhausted and sleeps for several hours after the symptoms have worn off. On waking, the person is well again.

In rare cases, the DER can be so severe that the victim dies from cardiovascular collapse and congestive heart failure. More than twenty such fatalities have been reported in medical literature. The threat of this frightening and severe reaction to alcohol is the basis for the use of disulfiram (Antabuse) as an adjunct in the treatment of alcoholism.

Significance

In 1949, Ruth Fox, a New York City psychoanalyst who specialized in the treatment of alcoholism, obtained enough disulfiram from colleagues in Denmark to treat about fifty alcoholic patients. In keeping with the current theories of that time, Fox used disulfiram in an aversion therapy Aversion therapy regimen, in which the patient was given alcohol in a hospital setting to induce the DER deliberately. This process was repeated several times on a weekly basis in an effort to produce a conditioned reflex against the use of alcohol by the alcoholic patient. By 1950, Fox considered discontinuing disulfiram therapy. It was apparent that aversion to alcohol was not occurring, several of her patients had almost died during a DER episode, and almost one-third of the patients complained of serious side effects (headaches, skin rash, impotence). It was quite clear that the only reason the patient remained sober was a fear of the disulfiram-ethyl alcohol reaction.

Fox decided to end the alcohol challenges that initiated the feared DER. Instead, she counseled patients about the severe reaction that would occur if they drank alcohol while taking disulfiram. Furthermore, she reduced the daily dose of disulfiram to a quarter of the recommended dose. Immediately after implementing these changes, patients’ complaints of side effects disappeared without the loss of the alcohol-deterring properties of daily administration of disulfiram. During her career, Fox used disulfiram to treat more than twenty-five hundred alcoholic patients; many responded with gratifying results. Antabuse—the proprietary brand name of disulfiram—is still the only drug currently approved by the FDA for specific treatment of alcoholism. Tens of thousands of people in the United States take Antabuse every day in their personal battle against alcoholism.

Antabuse therapy is not without controversy. Some physicians are reluctant to prescribe a drug that has the potential to induce a violent illness and possibly cause death if the patient ignores the doctor’s advice and drinks alcohol. Controlled studies have not shown Antabuse therapy to be more successful in helping alcoholics than conventional forms of counseling or group support programs run by AA.

All patients taking Antabuse must be cautioned to be on guard against “hidden alcohol” to avoid an accidental DER. Many medications, flavoring agents, and foods contain ethyl alcohol. Some cough syrups, mouthwashes, flavoring agents such as vanilla extract, and various desserts, sauces, and soups flavored with wines or liquors may contain enough alcohol to initiate a severe DER. Antabuse is not a panacea for treating all alcoholics or all forms of alcoholism; the drug does not stop or prevent the alcoholic’s desire to drink. The drug can help the motivated alcoholic who desperately wants to stop drinking.

By choosing Antabuse therapy, alcoholics only have to make one decision a day about drinking—whether or not to take the Antabuse pill. Alcoholics who take the pill know that “body chemistry” will keep watch over the next four or five days to help prevent the compulsive urge to drink. With this knowledge, Antabuse gives alcoholics time during the difficult transition and adjustment from alcoholism to a life of sobriety. Antabuse Disulfiram Medications;Antabuse (disulfiram) Alcoholism Drug therapy;alcoholism

Aversion Drug Found for the Treatment of Alcoholism Summary