ketamine treatment for ptsd and mdd in tbi

Conditions: PTSD, Post Traumatic Stress Disorder; Major Depressive Disorder; Traumatic Brain Injury

Summary: the goal of this clinical trial is to examine the use of sedative ketamine to treat depression and post-traumatic stress disorder (ptsd) in veterans with mild to moderate traumatic brain injury (tbi). the main questions it aims to answer are: * efficacy of ketamine to reduce symptoms of depression and/or ptsd * safety of ketamine to treat depression and/or ptsd in tbi participants will be randomly assigned to receive either ketamine or midazolam (active placebo) twice a week for 3 weeks. during participation, subjects will be interviewed, have lab tests, and complete rating scales, and questionnaires.


Eligibility criteria:
inclusion criteria: * willingness/able to sign informed consent. * able to read and write in english. * male or female veterans aged 18-55 years old. * remote history of tbi mild-moderate that is ≥12 weeks post-injury (chronic period) that met at minimum the 2021 va/dod clinical practice guideline for the management and rehabilitation of post-acute mild traumatic brain injury (i.e., new onset or worsening of at least one of the following clinical signs immediately following the event: loss or decreased of consciousness, period of posttraumatic amnesia, period of being dazed and confused, and neurologic deficits). * lifetime history of treatment resistance to at least one adequate trial of an antidepressant as determined by the massachusetts general hospital antidepressant treatment history questionnaire (mgh-atrq). * fda-approved antidepressant, trazodone, atypical neuroleptic, prazosin, or clonidine with stable treatment, as determined by the study clinician, for at least 4 weeks prior to randomization. following randomization, changes to doses may be allowable at the investigator's discretion exclusion criteria: * ketamine treatment within the last 6 months * lifetime history of psychosis-related disorder, current episode of mania/hypomania/mixed assessed by the mini-international neuropsychiatric interview (mini 7.0 for dsm-5). * history of penetrating head wounds or severe traumatic brain injury (glasgow coma scale \&lt;9; loss of consciousness \&gt;24hr; post-traumatic amnesia\&gt;7 days). * severe substance and/or alcohol use disorder (dsm-5-tr) within six months of initial assessment; presence of illicit drugs (except cannabis) by positive urine toxicology at screening. * intellectual disability or pervasive developmental disorder; dementia of any type. * any disorder that, based on the principal investigator\&#39;s judgement, would increase risk (e.g., unstable cardiac conditions) or protocol adherence (e.g., severe personality disorder). * for women: pregnancy (confirmed by lab test), initiation of female hormonal treatments within 3 months of screening, or inability/ unwillingness to use a medically accepted contraceptive method during the study. women who are surgically sterile or have been post-menopausal for at least 1 year will not be excluded * at screening, resting blood pressure (sitting or supine) lower than 90/60 or higher than 150/90, or resting heart rate lower than 45/min or higher than 100/min. * imminent risk of suicidal/homicidal ideation and/or behavior with intent and/or plan. * concurrent participation in a cognitive rehabilitation program, however patient will have a tbi clinician involved in directed services. * subjects on a prohibited medication: monoamine oxidase inhibitors, memantine, long acting benzodiazepines (i.e., chlordiazepoxide, diazepam, flurazepam)

Keywords: veteran ketamine ptsd depression tbi