Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

Co-occurring post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) is the most common response to trauma; it is associated with poor clinical outcomes and substantial human disability. Veterans with both PTSD and MDD (PTSD+MDD) have been shown to be at much greater suicidal risk than individuals with only one of these disorders. Ketamine given as repeated infusions has been shown to be effective in rapidly reducing PTSD and MDD symptoms in treatment resistant PTSD+MDD individuals. However, knowledge about the mechanisms underlying comorbid PTSD and MDD remain limited. The purpose of this study is to use repeated ketamine infusions as a probe to validate a model of PTSD+MDD that focuses on neuroanatomy and executive functioning.

This study is designed to better characterize the neurocognitive and associated functional connectivity mechanisms underlying comorbid post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) among veterans. Participants will be male/female veterans (18 to 75 years old) of any era or military background who suffer from chronic PTSD and MDD. Potential participants will be recruited from mental health clinics and screened for eligibility using a two stage process (phone/chart review, followed by interview). Participants with PTSD+MDD will undergo a series of baseline assessments including a baseline functional magnetic resonance imaging (fMRI) then be randomized to receive either 6 ketamine or 6 normal saline infusions on a Monday-Friday schedule over 3 weeks. On the day of infusion, participants will be required to stay at the clinical site for 2 hours after the infusion has been given. They will also be monitored via a phone call on the following day. After the infusion period has been completed participants will undergo a follow-up fMRI then 4 follow-up visits, up to 2 months. Additional participants will be enrolled in healthy control, depression only, and PTSD only groups and will only undergo baseline assessments, including a single fMRI.