Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD

This is an interventional treatment trial for PTSD focused on measuring ketamine, Written Exposure Therapy, PTSD, intervention, treatment, posttraumatic stress disorder Read More

Inclusion Criteria:

1. Men or women, 18-70 years of age;
2. 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;
3. Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS-5, and a past-month total CAPS5 score ≥ 25 at screening - this is done to ensure at least moderate severity and to safeguard against high placebo response rates;
4. 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);
5. Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;
6. Men who are sexually active with women of childbearing potential must use a medically accepted reliable means of contraception and must agree not to donate sperm for a period of 90 days after receiving the last dose of ketamine;
7. 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:

1. 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);
2. 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;
3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
4. Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinine clearance of >1.3 mg/dL;
5. Clinically significant uncorrected hypothyroidism or hyperthyroidism, as indicated by a TSH value 25% above or below the normal range;
6. A Body Mass Index (BMI) >40;
7. Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;
8. History of a neurodevelopmental disorder (e.g., autism, pervasive developmental disorder) ;
9. History of one or more seizures without a clear and resolved etiology;
10. Lifetime history of bipolar I or II disorder;
11. Presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;
12. Drug or alcohol use disorder within the preceding 3 months
13. Previous recreational use of ketamine or PCP on more than one occasion, or any recreational use of ketamine or PCP within the last two years;
14. Previous non-response to clinical or research ketamine or esketamine administration;
15. Current diagnosis of bulimia nervosa or anorexia nervosa;
16. Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
17. SBP >165 and DBP >95 at infusion days - higher BP allowed to account for stress or anxiety;
18. Concurrent treatment with opioid medication, or with long-acting or daytime short-acting benzodiazepines within two weeks of study start;
19. Current cognitive impairment, as defined by a score <23 on the Montreal Cognitive Assessment (MoCA);
20. Estimated IQ <80;
21. Currently receiving evidence-based psychotherapy for PTSD (e.g., prolonged exposure, cognitive processing therapy);

Note: Concurrent treatment with other psychotropic medications (including a short-acting benzodiazepine at bedtime only) will be permitted, but dose must be stabilized for at least three months before study start.