Progress in developing medications and strategies for treating addiction were juxtaposed with the challenges of implementing accessible and effective treatment programs at The State of the Art in Addiction Medicine conference conducted by the American Society of Addiction Medicine (ASAM) Nov. 1-3, 2001, in Washington, D.C. The conference, themed "From Molecules to Managed Care," was co-sponsored by the Center for Substance Abuse Treatment (SAT), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA).
Evaluating New Medications for Addiction Treatment
Ahmed el-Kashef, M.D., acting chief of the clinical/medical branch of the division of treatment research and development in NIDA, described NIDA's efforts to develop and evaluate agents to treat addiction. The program currently involves 55 medications in different phases of development, ranging from products marketed for other indications to new molecular entities developed for specific addictions. Among the agents being evaluated by NIDA for stimulant addiction are two investigational monoamine uptake inhibitors (MAOIs); the MAOI selegiline (Zelapar, Eldepryl); the antidepressants desipramine (Norpramin), sertraline (Zoloft) and venlafaxine (Effexor); dopamine agonists cabergoline (Dostinex) and amantadine (Symmetrel); serotonin antagonist ondansetron (Zofran); g-aminobutyric acid agonists tiagabine (Gabitril) and gabapentin (Neurontin); and catechol-O-methyltransferase inhibitor tolcapone (Tasmar). El-Kashef characterized the opioid agonist-antagonist buprenorphine (Subutex) -- alone and in combination with antagonist naloxone (Narcan) -- as well as the opioid antagonist naltrexone in depot formulation (Depotrex) as very promising agents for treatment of opiate addiction.
Although naltrexone (ReVia) is principally being evaluated as a means to support abstinence from opiate use, researchers outside the United States have employed it in protocols for rapid opiate detoxification. In a July 2001 press release, researchers in Brisbane, Australia, discussed findings from the first controlled trial of heroin-addiction treatment, contrasting rapid opiate detoxification with naltrexone and general anesthesia to methadone maintenance. The researchers characterized the naltrexone approach as less expensive and more effective at reducing heroin usage than conventional treatments. One of the researchers in the Australian study, John Saunders, M.D., professor of alcohol and drug studies at University of Queensland in Brisbane, commented to the press, "I am hoping that these trials and their results will provide considerable impetus to establish rapid detoxification and naltrexone-supported abstinence treatment as a viable treatment option."
El-Kashef indicated that NIDA is also investigating neuroendocrine, electrophysiological and neuroimage changes in response to addictive drugs and remedial measures. "New interest has arisen in biological markers of addiction to identify subtypes of patients who may respond differently to specific medications," he noted. "This approach may be promising in maximizing medication effect, or predicting relapse."
Also at the 2001 conference, Raye Litten, Ph.D., chief of the treatment research branch in the division of clinical and prevention research of NIAAA, described naltrexone and the glutamatergic modulator acamprosate (Campral) as the most promising and successful medications developed to date to treat alcoholism. "Although naltrexone is not a 'magic bullet,'" Litten explained, "it appears to have a moderate effect in reducing drinking, particularly decreasing relapse to heavy drinking."
The success of naltrexone for alcoholism may depend in part upon patient characteristics. A recently published trial (Krystal et al., 2001) in a mostly male Veterans Affairs population with chronic, severe alcohol dependence did not evidence benefit from naltrexone. In the multicenter, double-blind trial, 627 patients were randomized to receive either 12 months of naltrexone, 50 mg daily; three months of naltrexone followed by nine months of placebo; or 12 months of placebo. All patients were offered counseling and were encouraged to comply with the study medication regimen and attend Alcoholics Anonymous meetings.
At 13 weeks, the investigators found no significant differences between the groups in the number of days to relapse. Also, after 52 weeks, no difference in the groups was found in the percentage of days drinking or the number of drinks per drinking day. In an accompanying commentary supporting the use of naltrexone and offering reasons why the results from the Krystal et al. study may not be generalizable to all populations, Fuller and Gordis (2001) pointed out that recovering alcoholics who are married and employed are more likely to remain abstinent and that only one-third of this population had a spouse or live-in partner and, apparent from the disability pensions, only two-thirds appeared to be employed, both which possibly affected their motivation to stop drinking. Fuller and Gordis also questioned the adequacy of counseling in this study.
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