Major Depressive Disorder, Post-Traumatic Stress Disorders
Conditions
Keywords
ketamine, stress disorders, post-traumatic, stress disorders, traumatic, anxiety disorders, mental disorders, adjuvants, anesthesia, analgesics, anesthetics, anesthetics, dissociative, anesthetics, general, anesthetics, intravenous, excitatory amino acid agents, excitatory amino acid antagonists, hypnotics and sedatives, molecular mechanisms of pharmacological action, neurotransmitter agents, peripheral nervous system agents, pharmacologic actions, physiological effects of drugs, psychotropic drugs, sensory system agents, central nervous system agents, central nervous system depressants, depression, depressive disorder, depressive disorder, treatment-resistant, behavioral symptoms, mood disorders, therapeutic uses
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.
Interventions
DRUGKetamine
Six infusions of intravenous 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.
OTHERNormal Saline
Six infusions of intravenous normal saline solution over 3 weeks.
Sponsors
Minneapolis Veterans Affairs Medical Center
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Experimental versus Placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
For the PTSD+MDD group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Meets DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features 4. Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD \[meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)\] 5. If applicable, 6 weeks of stable antidepressants/augmenting agents 6. Sixth grade reading level 7. Ability to provide consent For the Healthy Controls group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features 4. Does not meet DSM-5 criteria for chronic PTSD or subthreshold PTSD 5. Not on medications for managing a psychiatric indication 6. Sixth grade reading level 7. Ability to provide consent For the Depression-only group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Experienced a traumatic event that meets DSM-5 criterion A for a diagnosis of PTSD but does not meet sufficient criteria (B-E) necessary for a diagnosis of PTSD or subthreshold PTSD 4. Meets criteria for MDD, single or recurrent, moderate-severe 5. If applicable, 6 weeks of stable antidepressants/augmenting agents 6. Sixth grade reading level 7. Ability to provide consent For the PTSD-only group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD \[meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)\] 4. Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features 5. If applicable, 6 weeks of stable antidepressants/augmenting agents 6. Sixth grade reading level 7. Ability to provide consent
Exclusion criteria
For the PTSD+MDD group,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | 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) | 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. |
Countries
United States
Outcome results
None listed