Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

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.

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
• 18 to 75 years old
• Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
• Does not meet DSM-5 criteria for chronic PTSD or subthreshold PTSD
• Not on medications for managing a psychiatric indication
• Sixth grade reading level
• Ability to provide consent

For the Depression-only group, inclusion criteria are:

• Female/Male veterans
• 18 to 75 years old
• 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
• Meets criteria for MDD, single or recurrent, moderate-severe
• If applicable, 6 weeks of stable antidepressants/augmenting agents
• Sixth grade reading level
• Ability to provide consent

For the PTSD-only group, inclusion criteria are:

• Female/Male veterans
• 18 to 75 years old
• 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)]
• Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
• If applicable, 6 weeks of stable antidepressants/augmenting agents
• Sixth grade reading level
• Ability to provide consent

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
• Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the Healthy Controls group, exclusion criteria are:

• Inability or unwillingness to provide written informed consent
• Moderate/severe cognitive impairment
• History of any major medical or psychiatric disorders
• 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
• Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the Depression-only group, exclusion criteria are:

• Inability or unwillingness to provide written informed consent
• Moderate/severe cognitive impairment
• Meet DSM-5 criteria for PTSD or subthreshold PTSD
• 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
• Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)

For the PTSD-only group, exclusion criteria are:

• Inability or unwillingness to provide written informed consent
• Moderate/severe cognitive impairment
• Meet DSM-5 criteria for a diagnosis of MDD, single or recurrent, moderate to severe
• 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
• Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)