Characterization of Comorbid Post-traumatic Stress Disorder and Major Depressive Disorder Utilizing Ketamine as an Experimental Medicine Probe
Overview
- Phase
- Phase 1
- Intervention
- Ketamine
- Conditions
- Post-Traumatic Stress Disorders
- Sponsor
- University of Minnesota
- Enrollment
- 67
- Locations
- 1
- Primary Endpoint
- Montgomery-Asberg Depression Rating Scale (MADRS)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For the PTSD+MDD group, inclusion criteria are:
- •Female/Male veterans
- •18 to 75 years old
- •Meets DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
- •Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD \[meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)\]
- •If applicable, 6 weeks of stable antidepressants/augmenting agents
- •Sixth grade reading level
- •Ability to provide consent
- •For the Healthy Controls group, inclusion criteria are:
- •Female/Male veterans
Exclusion Criteria
- •For the PTSD+MDD group, exclusion criteria are:
- •Inability or unwillingness to provide written informed consent
- •Moderate/severe cognitive impairment
- •Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
- •History of moderate or severe traumatic brain injury
- •History of comorbid substance disorder within 1 month of screening
- •Prior use of ketamine as an antidepressant
- •Clinically unstable medical illness
- •For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study
- •Imminent risk of suicidal/homicidal ideation and/or behavior
Arms & Interventions
Intravenous ketamine infusions
Six infusions of 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.
Intervention: Ketamine
Intravenous saline infusions
Six infusions of normal saline solution over 3 weeks.
Intervention: Normal Saline
Outcomes
Primary Outcomes
Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months.
Change in major depressive disorder symptoms over the course of the intervention.
PTSD Symptom Scale-Interview for DSM-5 (PSS-I-5)
Time Frame: At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months.
Change in post-traumatic stress disorder symptoms over the course of the intervention.