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Addiction Treatment Progress and Obstacles: Page 2 of 4

Addiction Treatment Progress and Obstacles: Page 2 of 4

While naltrexone is only the second agent to be approved by the U.S. Food and Drug Administration for treating alcoholism, some 50 years after approval of disulfiram (Antabuse), it is anticipated that acamprosate will soon be the third. Acamprosate is now approved for this indication in 40 countries. A New Drug Application is expected to be filed with the FDA in this year, according to Forest Laboratories, which would market acamprosate in the United States.

Acamprosate would offer not only a third option of therapeutic agents for alcoholism, but also a mechanism that differs from both the "reward circuit" blunting ascribed to naltrexone and the aversive effects of disulfiram. Acamprosate is thought "to inhibit the stimuli that can make alcohol 'negatively reinforcing,'" as alcohol levels in the central nervous system recede (Littleton and Mayer, 1999). In animals, it appears highly effective in inhibiting alcohol consumption prompted either by alcohol withdrawal or restriction.

In addition to affecting aspects of alcohol withdrawal, however, acamprosate exerts clinical effects independent of the presence of alcohol. At the 1999 State of the Art Conference, John Littleton, M.D., Ph.D., professor of pharmacology at University of Kentucky, described clinical findings with acamprosate. "Relapse actually seems to be prevented in many cases, rather than just ameliorated," he told attendees. "For this reason, it has been suggested that acamprosate may inhibit those cue-induced signs and symptoms that are very similar to withdrawal and that may precipitate relapse in abstinent alcohol dependent patients."

Litten has been enthusiastic about the clinical experience with acamprosate since that conference in 1999. "Alcoholic patients treated with acamprosate are more likely to complete treatment, have longer times to their first drink, and have higher abstinence rates than placebo-treated patients," he noted at the 2001 conference.

Litten also indicated that NIAAA is now investigating whether the combination of naltrexone and acamprosate is synergistic in treating alcoholism. The multi-site protocol contains tracks with acamprosate alone and in combination with naltrexone, and it also compares two types of behavioral/psychosocial therapies. Other promising agents under NIAAA research, Litten disclosed, include another opioid antagonist, nalmefene (Revex), and the serotonin (5-HT3) antagonist ondansetron.

"Development of more effective medications has the potential to vastly improve treatment outcome and reduce the suffering of millions of alcoholic patients and their families," Litten concluded.

Accessing and Succeeding in Treatment Programs

A recurrent issue at the conference was the gap between promising new treatments and the health and social policies that fail to provide addicts access to effective treatment programs. Suggesting one means of bridging the gap, Lee Dixon, director of the National Conference of State Legislatures' Health Policy Tracking Service, discussed recent RAND center research, indicating that the addition of full parity benefits for substance abuse and mental health care to private insurance plans can be accomplished with only a 3% to 4% increase in premium. The addition of only substance abuse benefits was estimated to result in a 0.3% increase.

The RAND study director, Roland Sturm, Ph.D., testified in July 2001, "Our results suggest that parity in employer-sponsored health plans is not very costly under comprehensively managed care, which is the standard arrangement in today's market place."

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