Zonisamide as a New Treatment for Co-occurring PTSD and AUD


Of the nearly 1.2 million Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF)/ Operation New Dawn (OND) Veterans who utilized VA health care services between 2002 and 2015, 31% were identified as having potential post-traumatic stress disorder (PTSD) [1]. Not only does PTSD decreases overall health, it also frequently leads to hazardous drinking [2]. Alcohol use disorder (AUD) poses a significant risk of physical and behavioral health issues related to combat service. AUD is the most prevalent substance use problem in the military and is considered to be the substance use concern of greatest significance to the military [3]. In fact, nearly half of OEF and OIF Veterans who screen positive for PTSD symptoms also report alcohol misuse [4, 5]. Because of the negative impact PTSD and AUD have on military readiness, psychological fitness, VA health care costs, and psychosocial function, effectively treating PTSD and AUD is important for the nation as a whole [3]. To this end, this study will evaluate the efficacy of zonisamide as a treatment for Veterans with combat-related PTSD and coexisting AUD.

Compared to individuals with PTSD or AUD alone, those with PTSD and coexisting AUD exhibit greater severity of PTSD and AUD symptoms. Comorbid PTSD and AUD is also associated with poorer quality of life, poorer recruitment and retention in treatment programs, poorer treatment outcomes, poorer treatment adherence, and shorter periods of abstinence post-treatment compared to either disorder alone. Although treatment of co-occurring AUD is vital for the effective management of PTSD, there is a lack of evidence on how best to treat for comorbid PTSD and AUD. In fact, PTSD treatment research has predominantly excluded patients with co-occurring AUD. Nonetheless, recent studies underscore the feasibility and importance of treating PTSD and AUD concurrently to facilitate improvements in PTSD symptoms and reductions in comorbid alcohol use.

Objective and Study Design:

The objective of this study is to determine the safety and potential efficacy of zonisamide, an experimental drug originally developed to treat epilepsy and seizure disorders, for treating AUD. Numerous clinical trials have shown that zonisamide doesn’t have the same side effects that other AUD drugs have. Researchers hope zonisamide will be a better drug for treating patients with AUD and reducing the symptoms of PTSD. 

The study will specifically examine the use of zonisamide for treating PTSD and AUD symptoms in 60 Veterans with co-occurring PTSD and AUD. Veterans will be divided into two groups, one which will get the experimental drug and another which will get a placebo. Both groups will be treated with either the drug or placebo for up to 7 weeks and then tested to see if the drug had any effect on the symptoms of PTSD and AUD.  


[1] Veterans Health Administration Office of Public Health (2015). Analysis of VA health care utilization among Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans: Cumulative from 1st Qtr FY 2002 through 2nd Qtr FY 2015 (October 1, 2001-March 31, 2015). Retrieved from: http://www.publichealth.va.gov/docs/epidemiology/healthcare-utilization-report-fy2015-qtr2.pdf

[2] McDevitt-Murphy ME, Williams JL, Bracken KL, Fields JA, Monahan CJ, Murphy JG (2010) PTSD symptoms, hazardous drinking, and health functioning among U.S.OEF and OIF Veterans presenting to primary care. J Trauma Stress 23:108-111.

[3] IOM, Institute of Medicine (U.S.). Committee on Prevention Diagnosis Treatment and Management of Substance Use Disorders in the U.S. Armed Forces., O'Brien C, Oster M, Morden E (2013) Substance use disorders in the U.S. Armed Forces. Washington, D.C.: National Academies Press.

[4] Ouiemette PC, Wolfe J, Chrestma KR (1996) Characteristics of post-traumatic stress disorder-alcohol abuse comorbidity in women. J Subst Abuse 8:335-346.

[5] Thomas JL, Wilk JE, Riviere LA, McGurk D, Castro CA, Hoge CW (2010) Prevalence of mental health problems and functional impairment among active component and National Guard soldiers 3 and 23 months following combat in Iraq. Arch Gen Psychiatry 67:614-623.

At a Glance

Study type:

Phase II Clinical Trial


To determine if zonisamide is a safe and efficacious treatment for PTSD and AUD



Number of Participants:

60 Veterans

Data Collection:


Participating Site:

Michael E. Debakey Veterans Affairs Medical Center (MEDVAMC)

Principal Investigator:

Christopher Verrico, Ph.D., Baylor College of Medicine (BCM)


18 months