Effective pharmacotherapies for the treatment of alcohol dependence do exist, but they must be combined with psychosocial treatment, according to a report by Dr. Michael Bogenschutz at a psychiatric symposium sponsored by the University of New Mexico.

(Dr. Bogenschutz is vice chair of addiction and substance abuse programs at the university.)

In reviewing the existing and upcoming pharmacotherapies, Dr. Bogenschutz noted that, unlike most other drugs of abuse, alcohol does not act on a single neurotransmitter system. Instead, it interacts with many receptor systems, including dopamine, serotonin, norepinephrine, glutamate, opioid, and γ-aminobutyric acid (GABA), rendering rational pharmacotherapy a difficult proposition.

Moreover, short-term and chronic use of alcohol can have widely disparate effects on some transmitter systems. Short-term use of alcohol causes increased dopamine release in the nucleus accumbens (a brain area involved in reward pathways), while chronic use leads to decreased dopamine release in that area. Short-term use leads to increases in GABA and endogenous opioids, but chronic use leads to decreases in those neurotransmitters.

Disulfiram (Antabuse®) works by inhibiting an enzyme critical in alcohol metabolism. If a patient drinks alcohol when taking disulfiram, he or she will experience sweating, headache, tachycardia, and decreases in blood pressure, potentially leading to circulatory collapse and death.

The Food and Drug Administration (FDA) approved disulfiram in 1951. Dr. Bogenschutz pointed out, “If disulfiram works, it works for the most part because people are afraid to drink alcohol. So until a person takes his first drink … it’s basically working as a placebo.”

Patients must be carefully counseled about the consequences of drinking alcohol while on Antabuse, and compliance should be carefully monitored. Side effects include peripheral neuropathy and hepatotoxicity, so liver enzymes must be monitored.

Naltrexone is thought to work by interfering with reward pathways in the brain. The drug has proven better than placebo in most studies, but efficacy depends upon compliance. Approved by the FDA in 1994, naltrexone may work only if patients sample alcohol and find it not to their liking.

“Patients who drank while taking naltrexone got as impaired as those not taking it, but they didn’t get as good a buzz. It didn’t feel as good,” Dr. Bogenschutz said.

Acamprosate is not yet approved in the United States but has been used in Europe for about a decade. It’s thought to work by reducing craving. The drug appears very safe; diarrhea is the most prominent side effect. It is now under FDA review.

Ondansetron, an FDA-approved antiemetic in cancer chemotherapy, is a 5-hydroxytryptamine₃ (5-HT₃) receptor blocker, and it may work by reducing craving in early-onset alcoholics. In a controlled trial, it appeared effective in reducing cravings in this population.

SSRIs (selective serotonin reuptake inhibitors) have been tested extensively for efficacy in alcohol dependence, mostly with disappointing results. If they work at all, they seem to do better in chronic, as opposed to early-onset, alcoholics.

Topiramate is an FDA-approved anticonvulsant that seemed to decrease alcohol consumption and craving in a single randomized, double blind, placebo-controlled trial involving 150 alcoholics.

Combination therapy in various forms is under active investigation. In particular, there is a large multicenter trial of acamprosate plus naltrexone underway in the United States. This study is also intended to evaluate two therapy conditions: (1) rigorous psychosocial treatment based on aspects of motivational enhancement therapy and cognitive-behavior therapy, and (2) a much briefer medication management model.

Taken from an article by Robert Finn, January 2004 issue of Addiction Psychiatry