Background: Veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have a high risk of developing post-traumatic stress disorder (PTSD). PTSD is very distressful and has a tremendous negative effect on one's family and social life. Many patients with PTSD try to escape their distress by drinking, and consequently alcoholism is a common problem in PTSD, which unfortunately just makes the disorder worse, with a more harmful negative impact. The antidepressant sertraline is a selective serotonin reuptake inhibitor (SSRI), which is the only medication approved for the treatment of PTSD. The use of SSRI medication is the recommended standard treatment for PTSD according to the Department of Veterans Affairs/Department of Defense clinical practice guidelines. However, recent experience has shown that SSRIs are not consistently effective in the treatment of PTSD. In alcoholics, SSRIs such as sertraline may benefit one subgroup of patients and actually increase alcohol use in another subgroup. This means that among veterans having both PTSD and alcohol use disorder, the recommended medication treatment for PTSD (sertraline) may benefit one subgroup of patients, but actually may be harmful and increase drinking in another subgroup of veterans. Research in the treatment of alcoholics who do not have PTSD suggests that those who drink more with SSRI treatment are those who have an underlying biological risk of alcoholism and psychiatric disturbance. The purpose of this study is to determine if we can identify which subgroup of patients having both PTSD and alcoholism may benefit from SSRIs and which subgroup may be susceptible to the harmful effects of SSRIs. We expect that a thorough assessment of the drinking patterns and emotional condition of veterans with PTSD and alcohol dependence will allow us to identify who can be expected to benefit and who would not benefit from sertraline treatment.

Research Strategy: All veterans participating in this research will be asked to participate in a 12-week treatment study. All participants will receive weekly cognitive behavioral therapy for PTSD and alcoholism, which provides standard forms of psychological therapy for these conditions. Participants also will be randomly assigned (like flipping a coin) to receive either sertraline or placebo (a sugar pill) during the 12-week treatment and participants will not be told which pill they are receiving. Therefore, veterans with PTSD and alcohol use disorder may benefit from the cognitive behavioral therapy, but we expect only a subgroup of those receiving sertraline will benefit from the medication. Another subgroup receiving sertraline actually may not do as well as subjects assigned to receive placebo. However, these conclusions will be known only after the study is completed and the results are analyzed, which may take 5 years to complete.

Importance of This Work: Given the frequency and severity of PTSD in OEF/OIF veterans and the common co-occurrence of alcohol dependence, it is extremely important to identify medications that can help veterans who suffer with these disorders. Since no treatment is universally effective, it is even more important to identify which population subgroups may benefit from a particular medication and to identify if there is a subgroup for whom a particular medication may actually be harmful. Given the frequent use of SSRIs in PTSD and veterans who drink, the proposed study is critical to help us better understand the safe and effective use of sertraline or other SSRIs.