Alcoholism-treatment medication acamprosate may help abstinent alcoholics sleep better

August 27, 2006

Alcoholics generally don't sleep well. Nor does abstinence improve the situation much. In fact, sleep difficulties during alcohol abstinence may be responsible for a relapse to alcoholism as individuals attempt to self medicate their sleeping problems. New findings show that an alcoholism-treatment drug called acamprosate, widely used in Europe, can alleviate post-withdrawal sleep disturbances by influencing glutamatergic transmission.

Results are published in the September issue of Alcoholism: Clinical & Experimental Research.

"During chronic and excessive use of alcohol, short periods of deep sleep become interrupted by brief periods of restlessness," said Luc Staner, director of the Sleep Laboratory of the Centre Hospitalier de Rouffach. "This may also be accompanied by sleep terrors, sleepwalking and exacerbation of loud snoring or sleep apnea. During the day, alcohol intake can exacerbate sleepiness, which disrupts performance and contributes to accidents even when an individual is not significantly intoxicated." Staner is also a researcher at FORENAP, an organization that specializes in early drug development and research in neuroscience, located in Rouffach, France.

Sleep dysfunction does not necessarily improve with abstinence from alcohol, added Staner, who is also the corresponding author for the study. "Sleep is initially characterized by occasional nights of very little sleep and nightmares, followed by either progressive improvement or, very often, long-lasting sleep difficulties," he said. "If the latter, consequences may include decreased attention, vigilance, energy and concentration; increase in fatigue and malaise, irritability, etc. These often protracted symptoms lead some patients to resume drinking in an attempt to self-medicate their sleep problems. Probably for this reason, persistent post-withdrawal sleep complaints have been shown to predict relapse to alcoholism."

"These sleep problems among abstinent alcoholics construe a critical issue, as they can remain for up to three years," added Timothy A. Roehrs, director of research at the Sleep Disorders and Research Center at Henry Ford Hospital, as well as professor of psychiatry and neurobehavioral sciences at Wayne State University School of Medicine in Detroit. "This would be the first study of its kind to show positive effects of acamprosate on sleep disorders."

The seemingly greater popularity of acamprosate in Europe, noted Staner, is probably due to the fact that the drug was approved by many European countries in the early 1990s, long before naltrexone (another alcoholism-treatment medication). "The drug is very safe to use and there is no cross-tolerance with alcohol," he said.

Study participants (n=24 males) were recruited through physician referral or a local hospital outpatient department; all were confirmed as alcohol dependent according to the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition. Beginning eight days before alcohol withdrawal, in order to reach steady levels in patient plasma, and continuing for 15 days following withdrawal, researchers administered either acamprosate (two tablets of 333 mg) or a placebo. Polysomnographic assessments were recorded during acute withdrawal (the first two nights following withdrawal), as well as during post-withdrawal abstinence (the last two nights of the study period).

"Compared to the placebo," said Staner, "results indicate that acamprosate objectively improves sleep disturbances of alcohol-dependent patients who are trying to stop alcohol intake. This effect was observed during the first withdrawal night and was maintained after two weeks of treatment. On a more mechanistic level, these results appear to implicate glutamate in both sleep disturbances and withdrawal symptoms, and acamprosate appears to be able to decrease the physiological effects of glutamate in the brain."

Given that this was a very short-term study, Roehrs said he is hopeful that future research will address what the long-term impact of acamprosate may be. He would also like to learn more about helping those individuals for whom acamprosate does not alleviate sleep problems.
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Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "The Effects of Acamprosate on Sleep During Alcohol Withdrawal: A Double-Blind Placebo Controlled Polysomnographic Study in Alcohol-Dependent Subjects," were: Peter Boeijinga, IsabelleGendre, Muriel Muzet and Rémy Luthringer of FORENAP at Centre Hospitalier de Rouffach, France; Thierry Danel of the Unité de psychopathologie et alcoologie clinique de l'anxiété of Lille, France; and Frédéric Landron of MERCK Santé of Lyon, France. The study was funded by Merck Santé.

Alcoholism: Clinical & Experimental Research

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