The purpose of this study is to see whether ketamine, when given repeatedly via the nose
(intranasally), can produce a quick and persistent improvement in PTSD symptoms. At higher
doses, ketamine has been used for many years as an anesthetic for medical procedures, and at
lower doses may be an effective treatment in patients with major depression and PTSD.
Inclusion Criteria:
- Men or women, 18-65 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-5 criteria for current civilian or combat-related PTSD,
based on clinical assessment by a study psychiatrist and on the CAPS - this is done
to ensure at least moderate severity and to safeguard against high placebo response
rates;
- 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
prior to each intranasal administration;
- 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
intranasal administration day;
- Use of evidence-based individual psychotherapy (such as prolonged exposure) during
the study;
- History 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; a rather narrow
time period was chosen, however, in order 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; this is
the same period of time that we used in our recently completed study of IV ketamine
for PTSD.
- 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
- Patients who report current treatment with a benzodiazepine, an opioid medication, or
a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to
randomization; patients taking stable doses of antidepressant medication for 3 months
prior to randomization will be allowed.
- For subjects who may participate in the MRI portion of the study, claustrophobia, any
trauma or surgery which may have left magnetic material in the body, magnetic
implants or pacemakers, and inability to lie still for 1 hour or more.
