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.