WHITE RIVER JUNCTION, VT — A combination of prolonged exposure (PE) and topiramate, a medication developed to treat seizures, was more effective than PE and placebo in lessening posttraumatic stress disorder (PTSD) symptoms, according to a new study.
The report in the American Journal of Psychiatry noted that PTSD and alcohol-use disorder (AUD) frequently co-occur.1
Researchers led by the VA’s National Center for PTSD in White River Junction, VT, added that PE is an effective treatment for PTSD but shows less success in patients with co-occurring AUD. “Topiramate may help reduce alcohol use and PTSD symptoms,” they suggested.
Their double-blind, placebo-controlled outpatient clinical trial compared 12 sessions of PE plus either topiramate or placebo. The study also had participation from the VA Center of Excellence for Stress and Mental Health in San Diego, VA San Diego Healthcare System, James A. Haley Veterans Hospital in Tampa, FL, San Francisco VA Healthcare System and VA Puget Sound Healthcare System in Seattle.
The study team randomly assigned 100 U.S. veterans with PTSD+AUD to 16 weeks of treatment with PE+topiramate (up to 250 mg) or PE+placebo to examine effects on alcohol use and PTSD severity at post-treatment assessment and at 3- and 6-month follow-ups. The participants had a mean age of 45, and were 84% men.
The results indicated that the percentage of heavy drinking days decreased significantly for both conditions but did not differ between groups. The authors noted that PTSD scores were lower in the PE+topiramate group than in the PE+placebo group at post-treatment assessment but not at follow-ups, adding, “The same patterns were observed for loss of PTSD diagnosis and meaningful PTSD symptom change. Change in secondary outcomes (depression, quality of life) did not differ between conditions.”
The study concluded that PE+topiramate was associated with a greater reduction in PTSD symptoms than PE+placebo during active treatment. “The addition of topiramate led to more rapid and pronounced PTSD symptom reduction, which may be of benefit to patients,” the researchers pointed out. “Because effects of topiramate were not maintained at longer-term follow-up, extending time on topiramate or additional strategies to prolong such effects may be useful. Topiramate did not show added benefit to PE for percent heavy drinking days or secondary outcomes.”
- Norman SB, Luciano MT, Panza KE, Davis BC, et. Al. A Randomized Clinical Trial of Prolonged Exposure Therapy With and Without Topiramate for Comorbid PTSD and Alcohol Use Disorder. Am J Psychiatry. 2025 Mar 19:appiajp20240470. doi: 10.1176/appi.ajp.20240470. Epub ahead of print. PMID: 40103353.
