ALBUQUERQUE -- Effective pharmacotherapies for the treatment of alcohol dependence do exist, but they must be combined with psychosocial treatment, Dr. Michael Bogenschutz reported at a psychiatric symposium sponsored by the University of New Mexico.
In reviewing the existing and upcoming pharmacotherapies, Dr. Bogenschutz, vice chair of addiction and substance abuse programs at the university, 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 [gamma]-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 aldehyde dehydrogenase, 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 approved disulfiram in 1951, but clinical trials on its effectiveness have been mixed at best. Metaanalyses seem to show little benefit over placebo, but 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 when on disulfiram, and compliance must be carefully monitored. This is eased somewhat by the drug's long half-life. Patients can come to the office three times a week to receive their doses (typically 250 mg/day) while being watched by office staff.
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 proved better than placebo in most studies, but, once again, efficacy depends on compliance.
"Patients who drank while taking naltrexone got as impaired as those not taking naltrexone, but they didn't get as good a buzz. …