Topiramate Treatment of Alcohol Use Disorders in Veterans With PTSD: A Pilot Controlled Trial of Augmentation Therapy

The goal of the proposed project is to improve the treatment of veterans with co-occurring
PTSD and alcohol dependence. Exposure to the stresses of combat is known to be associated
with risk for both PTSD and alcohol and other substance use. PTSD and alcohol use disorders
occur frequently among returning OEF/OIF veterans. Alcohol and substance use are risk
factors for the development of PTSD, moderators of PTSD symptom severity, and potential
consequences of PTSD. Alcohol is by far the most common substance of abuse in patients with
PTSD, and its use may represent an attempt by PTSD patients to "self-medicate" symptoms such
as hyperarousal. However, to date there has been little research to develop
pharmacotherapies that would, ideally, reduce both alcohol use and PTSD symptoms.

Topiramate is one of the few medications for alcohol dependence that has also been tested as
a potential medication to treat PTSD. Topiramate's efficacy in alcohol dependence has been
shown in two recent large controlled trials. Several open trials have suggested that
topiramate may be effective in reducing PTSD symptoms while the results of two small
controlled trials have been mixed.

A clinical trial of topiramate is therefore indicated in order to achieve the following
specific aims:

The primary aim is to obtain a preliminary assessment of the efficacy of topiramate in
increasing the percent of days abstinent from alcohol use from baseline to the end of
treatment in veterans with PTSD and alcohol abuse/dependence who are drinking heavily.

The secondary aim is to obtain a preliminary assessment of the efficacy of topiramate in
increasing the percent of days abstinent from alcohol as compared to placebo.

Additional aims include the following:

- To obtain a preliminary assessment of the efficacy of topiramate in reducing other
measures of alcohol use such as percent heavy drinking days, number of drinks per week,
number of drinks per drinking day, and alcohol craving.

- To obtain a preliminary assessment of the efficacy of topiramate in reducing PTSD
symptom severity in veterans with chronic PTSD and alcohol abuse/dependence.

- Informing the design of a planned subsequent larger controlled trial of topiramate in
veterans with chronic PTSD and alcohol abuse/dependence

- To obtain an estimate of topiramate vs. placebo effect size for future studies. B. To
obtain a preliminary assessment of the effects of topiramate treatment on measures of
risk-taking behavior in veterans with chronic PTSD and alcohol abuse/dependence.

To achieve these aims, we will conduct a prospective, parallel groups, randomized,
double-blind, placebo-controlled flexible-dose pilot clinical trial of topiramate in
veterans with PTSD and alcohol abuse/dependence who are already receiving standard treatment
for PTSD but still drink heavily. The primary treatment outcome will be percent days
abstinent from alcohol; secondary outcomes will include other alcohol use measures, PTSD
symptom severity, adverse effects, recruitment and retention rates.