Ketamine as a Rapid Treatment for Post-traumatic Stress Disorder (PTSD)
Randomised, quadruple-blind crossover trial (n=41) comparing single IV ketamine 0.5 mg/kg to midazolam 0.045 mg/kg for treatment of PTSD.
Detailed Description
This randomised, quadruple-blind crossover study tested whether a single intravenous infusion of ketamine (0.5 mg/kg over 40 minutes) reduces core PTSD symptoms compared with active comparator midazolam (0.045 mg/kg IV).
Forty-one participants with DSM-IV PTSD (CAPS score ≥50) received two single-dose infusions in a crossover design with clinical and cognitive assessments; memory impairment during infusion was examined as a predictor of clinical response.
Safety monitoring emphasised acute cardiovascular effects and transient intoxication; previous work indicates limited adverse effects other than transient dissociation and increases in blood pressure.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
Ketamine
experimentalSingle IV infusion 0.5 mg/kg over 40 minutes; crossover design.
Interventions
- Ketamine0.5 mg/kgvia IV• single dose• 1 doses total
Infused over 40 minutes
Midazolam
active comparatorSingle IV infusion 0.045 mg/kg over 40 minutes (active comparator).
Interventions
- Placebo0.045 mg/kgvia IV• single dose• 1 doses total
Midazolam 0.045 mg/kg IV, infused over 40 minutes; recorded as active comparator (compound stored as placebo reference)
Participants
Inclusion Criteria
- Men or women, 21-55 years of age;
- Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;
- Participants must fulfill DSM-IV criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS (score must be at least 50 at screening and prior to each infusion - this is done to ensure at least moderate severity and to safeguard against high placebo response rates); additionally, clinicians will use clinical judgment to assess if patients are symptomatic enough to receive each infusion;
- Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);
- Women of childbearing potential must have a negative pregnancy test at screening and pre-infusion;
- Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).
Exclusion Criteria
- Women who plan to become pregnant, are pregnant or are breast-feeding;
- Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease (including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury);
- Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
- Patients with uncorrected hypothyroidism or hyperthyroidism;
- Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;
- Use of evidence-based individual psychotherapy (such as prolonged exposure) and other non-pharmacological treatments during the study;
- Histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
- History of one or more seizures without a clear and resolved etiology;
- History of (hypo)mania;
- Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;
- Drug or alcohol abuse or dependence within the preceding 3 months;
- Previous recreational use of ketamine or PCP;
- Current diagnosis of bulimia nervosa or anorexia nervosa;
- Diagnosis of schizotypal or antisocial personality disorder;
- Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
- A blood pressure of one reading over 160/90 or two separate readings over 140/90 at screen or baseline visits.
Study Protocol, Arms & Participants
Go Pro to access detailed study protocol timelines, treatment arms, dosing schedules, and participant eligibility criteria.
Locations
Related Publications
Your Personal Research Library
Go Pro to save trials, add notes, rate research, and organize custom shelves.