Clinical TrialPTSDKetaminePlaceboCompleted
Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans
Randomised, double-blind, placebo-controlled parallel trial (n=67) of six IV ketamine infusions (0.5 mg/kg) over 3 weeks in veterans with comorbid PTSD and MDD to probe neuroanatomy and executive functioning.
Target Enrollment
67 participants
Study Type
Phase I interventional
Design
Randomized, double Blind
Registry
Detailed Description
This randomised, double-blind, placebo-controlled parallel trial will enrol veterans with chronic comorbid PTSD and MDD and randomise them to six intravenous ketamine infusions (0.5 mg/kg) or normal saline over three weeks to investigate neuroanatomical and executive-function mechanisms using fMRI and neurocognitive testing.
Participants remain onsite for approximately two hours after each infusion, are contacted by phone the following day, and undergo a follow-up fMRI and four visits up to two months; additional healthy control, depression-only, and PTSD-only cohorts undergo baseline assessments including a single fMRI.
Study Protocol
Preparation
sessions
Dosing
6 sessions
120 min each
Integration
sessions
Study Arms & Interventions
IV ketamine
experimentalSix intravenous infusions of ketamine 0.5 mg/kg over 3 weeks.
Interventions
- Ketamine0.5 mg/kgvia IV• six infusions• 6 doses total
0.5 mg/kg per infusion; Monday–Friday schedule over 3 weeks.
IV saline
inactiveSix intravenous normal saline infusions over 3 weeks (placebo comparator).
Interventions
- Placebovia IV• six infusions• 6 doses total
Normal saline placebo comparator.
Participants
Ages
18 – 75
Sexes
Male & Female
BMI
-
Psychosis History
-
Inclusion Criteria
- 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
- Exclusion Criteria:
- For the PTSD+MDD group, exclusion criteria are:
- 1. Inability or unwillingness to provide written informed consent
- 2. Moderate/severe cognitive impairment
- 3. 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
- 4. History of moderate or severe traumatic brain injury
- 5. History of comorbid substance disorder within 1 month of screening
- 6. Prior use of ketamine as an antidepressant
- 7. Clinically unstable medical illness
- 8. 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
- 9. Imminent risk of suicidal/homicidal ideation and/or behavior
- 10. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)
- For the Healthy Controls group, exclusion criteria are:
- 1. Inability or unwillingness to provide written informed consent
- 2. Moderate/severe cognitive impairment
- 3. History of any major medical or psychiatric disorders
- 4. 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
- 5. History of moderate or severe traumatic brain injury
- 6. History of comorbid substance disorder within 1 month of screening
- 7. Prior use of ketamine as an antidepressant
- 8. Clinically unstable medical illness
- 9. 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
- 10. Imminent risk of suicidal/homicidal ideation and/or behavior
- 11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)
- For the Depression-only group, exclusion criteria are:
- 1. Inability or unwillingness to provide written informed consent
- 2. Moderate/severe cognitive impairment
- 3. Meet DSM-5 criteria for PTSD or subthreshold PTSD
- 4. 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
- 5. History of moderate or severe traumatic brain injury
- 6. History of comorbid substance disorder within 1 month of screening
- 7. Prior use of ketamine as an antidepressant
- 8. Clinically unstable medical illness
- 9. 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
- 10. Imminent risk of suicidal/homicidal ideation and/or behavior
- 11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)
- For the PTSD-only group, exclusion criteria are:
- 1. Inability or unwillingness to provide written informed consent
- 2. Moderate/severe cognitive impairment
- 3. Meet DSM-5 criteria for a diagnosis of MDD, single or recurrent, moderate to severe
- 4. 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
- 5. History of moderate or severe traumatic brain injury
- 6. History of comorbid substance disorder within 1 month of screening
- 7. Prior use of ketamine as an antidepressant
- 8. Clinically unstable medical illness
- 9. 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
- 10. Imminent risk of suicidal/homicidal ideation and/or behavior
- 11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)