Fran Lowry

December 10, 2012

AVENTURA, Florida — An anticonvulsant approved for the treatment of epilepsy and migraine is also showing promise in the treatment of alcohol dependence, new research shows.

Investigators at the University of California, San Francisco, and San Francisco Veterans Administration (VA) found that in veterans with posttraumatic stress disorder (PTSD), topiramate significantly reduced alcohol consumption.

Combat exposure is a known risk for both PTSD and alcohol or other substance use, said study investigator Steven L. Batki, MD.

Dr. Steven Batki

"The co-occurrence of PTSD and alcohol dependence is a major problem facing veterans seen in the VA system, and at the present time, while there are some effective pharmacotherapies for alcohol dependence and there are some modestly effective medication treatments for PTSD, there's been very little work done looking at integrated pharmacotherapeutic treatment for veterans who have both alcohol dependence and PTSD," Dr. Batki told Medscape Medical News.

Robust Treatment

For the pilot study, which was funded by the US Department of Defense and the Northern California Institute for Research and Education, Dr. Batki and colleagues randomly assigned 30 veterans with PTSD and alcohol dependence to 12 weeks of treatment with topiramate or placebo.

"Topiramate has been established as a fairly robust treatment for alcohol dependence, with effect sizes that may rival or be greater than that found for other alcohol treatment medications, such as disulfiram, acamprosate, or naltrexone.

"Moreover it's been a medication that has been studied, although only in some small studies, both open and controlled, for the treatment of PTSD with some mixed but generally positive findings," Dr. Batki said.

In addition, both study groups received weekly medication management and alcohol counseling sessions.

Most (28/93%) of the study participants were male, their ages ranged from 25 to 65 years (mean age, 50 years), and 73% had combat-related PTSD. Most had very high Clinician-Administered PTSD Scale (CAPS) scores, indicating severe PTSD, Dr. Batki said.

Fifty percent of the participants were veterans of Vietnam, 20% were veterans of the Iraq and Afghanistan wars, and the rest were veterans of the Korean and other wars. Twenty of the study participants were receiving disability benefits from Social Security.

The participants were heavy drinkers and reported a mean of 10.6 drinks per day at baseline.

Alcohol use, PTSD symptoms, other psychological symptoms, and adverse effects were measured weekly.

Not an Easy Drug to Take

Preliminary findings showed that topiramate treatment resulted in significantly fewer drinking days per week than placebo (1.4 vs 2.8 drinking days; P = .037) and also showed a trend for fewer drinks per week than placebo (13.3 vs 21.8 drinks per week; P = .095).

The group receiving topiramate also showed significantly lower alcohol craving on the Obsessive-Compulsive Drinking Scale (P = .004).

Topiramate was also associated with higher retention, with a mean of 11.5 weeks vs 9.6 weeks for placebo (P < .05) and medical adherence (P < .05).

However, PTSD symptoms were not significantly lowered in the topiramate group (P = .117).

Dr. Batki said that these preliminary results are encouraging and that the study is continuing with larger numbers of participants.

"We've been funded through a Department of Defense grant to do a larger, 150-subject 4-year study that is in its beginning phase," he said. "We are also extending this study of alcohol use in veterans who have mild traumatic brain injury, again with the aim of trying to reduce alcohol use in this group and improve outcomes."

Dr. Batki added this caveat: "Topiramate is not an easy drug to take. It has side effects, and it is contraindicated in individuals with narrow angle glaucoma or with a history of kidney stones. It also produces transient decrements in concentration and memory, so that has to be balanced against its potential benefits."

Heavy drinking also can produce such adverse cognitive effects, "but one needs to be balanced in presenting the pros and cons," he said.

Two Birds With 1 Stone

Dr. William Lawson

Commenting on the study for Medscape Medical News, William B. Lawson, MD, PhD, professor and chair of the Department of Medicine, Howard University, Washington, DC, said that the current study confirms work from other researchers.

"Some investigators have been pushing the idea that topiramate is a very useful drug for alcohol, especially in active drinkers, and this is a very nice study because it shows that another group is showing the same effect. And most importantly, as they note, comorbidity is the nature of the game," said Dr. Lawson.

"It's not enough to get people to stop drinking, but also to try to treat some of the other psychopathology, namely the PTSD, that may be causing them to self-medicate with alcohol," he added.

He agreed that this study merits further follow-up.

"If we can kill 2 birds with 1 stone, it will be a great advance in terms of helping not only veterans but also people in the general community with posttraumatic stress disorder who are trying to deal with that with excessive drinking."

The study was supported by the US Department of Defense and the Northern California Institute for Research and Education. Dr. Batki and Dr. Lawson have disclosed no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 23rd Annual Meeting & Symposium. Paper presentation 3. Presented December 8, 2012.