Ketamine as a Rapid Treatment for Post-traumatic Stress Disorder (PTSD)
Condition: Stress Disorders, Post-Traumatic; PTSD; Depression; Anxiety Disorder
MeSH terms: Depression; Stress Disorders, Traumatic; Anxiety Disorders; Stress Disorders, Post-Traumatic
Intervention: Midazolam; Ketamine
Intervention description: single dose 0.045 mg/kg IV infused over 40 minutes; Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes
Intervention MeSH terms: Midazolam; Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 41.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Stress Disorders, Post-Traumatic; PTSD; anxiety disorder; ketamine; depression; depressed mood

Summary:

      The objective of the proposed study is to test if a single IV dose of ketamine (0.5 mg/kg)
      decreases symptoms of PTSD.
    

Eligibility criteria:

        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 (because the
             medical risk of using ketamine during pregnancy and breast-feeding is unknown);

          -  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 (given that this
             might otherwise contribute to their symptoms, however, a rather narrow time period was
             chosen such as to allow participation by individuals with a history of substance abuse
             or dependence problems that could be secondary to their PTSD, and to more closely
             approximate patients seen in real-world settings);

          -  Previous recreational use of ketamine or PCP;

          -  Current diagnosis of bulimia nervosa or anorexia nervosa;

          -  Diagnosis of schizotypal or antisocial personality disorder (since these are known to
             reduce the possibility of study completion; other Axis II diagnoses will be allowed);

          -  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.