PROlonGed ExpoSure Sertraline

Randomized Trial of Sertraline, Prolonged Exposure, and Their Combination for Post-traumatic Stress Disorder (PTSD) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF).

The current research study aims to compare the effectiveness of two proven treatments for posttraumatic stress disorder (PTSD): Prolonged Exposure (PE), sertraline, and their combination. In addition, the investigators are examining predictors of response to these two treatments and how PTSD symptoms, thoughts, and biological factors may be changed by such treatments. Biological mechanisms of change are also examined including emotion processing and regulation in fMRI, HPA axis function, and genetics and genomics. In addition, the investigators will examine acceptability of each treatment and reasons for ending treatment.

Inclusion Criteria:

• Patient is an Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combat veteran with chronic posttraumatic stress disorder (PTSD) or significant PTSD symptoms (Clinician Administered Posttraumatic Stress Disorder Scale [CAPS] >= 50) of at least 3 months duration

Exclusion Criteria:

• Current, imminent risk of suicide (as indicated on C-SSRS)
• Active psychosis
• Alcohol or substance dependence in the past 8 weeks
• Unable to attend regular appointments
• Prior intolerance or failure of adequate trial of prolonged exposure (PE) or sertraline (SERT) (defined as at least 2 months of SERT at least 100mg/day)
• Medical illness likely to result in hospitalization or for which treatments are contraindicated (based on lab results, medical history and physical exam)
• Serious cognitive impairment (as evidenced by cognitive impairment felt likely to interfere with the ability to participate meaningfully in the study)
• Concurrent antidepressants or antipsychotics
• Pregnant females