Nancy A. Melville

December 09, 2013

SCOTTSDALE, Arizona — The anticonvulsant gabapentin improves 2 sleep variables that play an important role in alcohol dependence relapse, new research shows.

"These results are consistent with the hypothesis that improved drinking outcomes with gabapentin may be related to improvement in sleep measures that can be measured objectively with polysomnography," said lead author Kirk Brower, MD, a professor of psychiatry at the University of Michigan Medical School and executive director of the University of Michigan Addiction Treatment Services, in Ann Arbor.

The findings build on those from a randomized, double-blind, placebo-controlled trial of 150 patients published just last month, in which a 12-week regimen of oral gabapentin 900 mg or 1800 mg per day and concomitant counseling showed efficacy in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a positive safety profile ( JAMA Intern Med. Nov. 4, 2013).

The findings were presented here at the American Academy of Addiction Psychiatry (AAAP) 24th Annual Meeting & Symposium.

Promising Treatment

"The study, and a previous trial, showed improved sleep in alcohol-dependent patients and reduced drinking, so gabapentin looks like a very promising medication for this," Dr. Brower said.

"But the studies didn't have objective sleep measures with polysomnography, so we don't really know if gabapentin's effects are due to just sedation or some other mechanism on sleep, so we sought to find out about that in our study."

In the new study, 49 alcohol-dependent participants (10 women and 39 men) were randomly assigned to receive either 1500 mg of gabapentin nightly (n = 25) or placebo (n = 24) for 1 week and were then followed for 3 months.

All of the patients were assessed with polysomnography in a sleep laboratory during 3 consecutive nights on 2 occasions ― the first just before starting the medication, and the second 1 week after the start of medication.

The first night of the 3-night regimen served as adaptation to the sleep evaluation, the second represented baseline sleep, and on the third night, patients were subjected to a sleep challenge, in the form of a 3-hour sleep delay.

The medication was discontinued after the last night of the second regimen.

The participants who experienced relapse, defined as a return to drinking by 3 months, had significantly less stage 2 sleep than abstainers (50.3% vs 55.4%; P = .04); however, those in the gabapentin group had significantly increased stage 2 sleep compared with those in the placebo group (P = .008).

In addition, patients who relapsed spent more time awake after sleep onset than abstainers (27.6 vs 14.5 minutes; P = .004), but the amount of time was decreased in the gabapentin group (P = .003) compared with the placebo group.

"The study is the first to show an association between gabapentin and polysomnograph sleep measures that are correlated with abstinence of alcohol use," Dr. Brower said.

Enormous Problem

Efforts to better understand and address sleep issues in patients with alcohol and other addictions are essential because of the high prevalence of insomnia in the population, said Steven L. Batki, MD, a professor of in the University of California, San Francisco's, Department of Psychiatry and director of the Addiction Research Program.

"Insomnia is an enormous problem in individuals with addiction and is frequently cited by patients as a reason for their relapse into alcohol use," he told Medscape Medical News.

Randomized, controlled trials looking at the issue of insomnia in alcohol abuse have been lacking, and although most have focused on 3 drugs ― trazodone, quetiapine, and gabapentin ― sleep reports have been mainly subjective, and gabapentin has shown the strongest results in treating insomnia in substance abuse.

"Previously, studies showed gabapentin helped reduce drinking and improve sleep, but there's been no objective verification of that or understanding of what part of sleep is improved," Dr. Batki said.

"So what's important about this is that it's the first study looking at objective sleep measures, and while limitations include that it is a small study and not a treatment study, it's a direct indication of potential mechanisms in which gabapentin might help reduce alcohol abuse by improving these 2 sleep parameters that seem to be correlated with the relapse to alcohol."

The study received funding from National Institute of Health grants K24 AA00304 and R01 AA016117. Dr. Brower disclosed no relevant financial relationships. Dr. Batki disclosed that he has consulted for Consultant Gilead Sciences and for Alta Mira Recovery Programs.

American Academy of Addiction Psychiatry (AAAP) 24th Annual Meeting & Symposium: Presented December 7, 2013.

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