Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

• Status: Recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Minnesota; University of Minnesota - Clinical and Translational Science Institute
• Collaborator: Minneapolis Veterans Affairs Medical Center
• Treatments: Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acids; Ketamine; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Pharmaceutical Solutions

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:

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.)