Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Controlled Trial of Repeated-Dose Intravenous Ketamine for PTSD
Brief Summary: The purpose of this study is to study new ways to treat post-traumatic stress disorder (PTSD). Current treatments for PTSD do not work for everyone and it can take time to determine whether a person responds to a chosen treatment. The purpose of this study is to see whether ketamine, when given repeatedly intravenously 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. Ketamine given for PTSD is investigational, which means that the FDA has not yet approved the drug for treating this condition. In this study, the effects of ketamine will be compared to those of midazolam. Midazolam has similar acute anesthetic effects compared to ketamine but has not been shown to treat or alleviate any symptoms of PTSD. This makes midazolam an appropriate substance to gauge whether ketamine can treat or alleviate PTSD symptoms thereby acting as what we call an active control.


Options:
A: Inclusion Criteria:

* Female between 21-65 years of age
* Able to provide consent and willing to participate in research
* Fulfills Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for primary diagnosis of PTSD
* PTSD duration of illness at least 3 months
* Able to provide consent and willing to participate in research
* CAPS score of ≥ 50 at Screening and Visit 3 (randomization)
* Negative Urine toxicology test
* Agrees to use protocol-defined effective birth control method
* If the patient has a history of peptic ulcer disease (PUD), there is documentation of the etiology of the PUD and that effective treatment was provided with full eradication of ulcers and symptoms

Exclusion Criteria:

* Lifetime or current diagnosis of schizophrenia or other psychotic disorder, bipolar disorder, obsessive compulsive disorder (OCD), or current Axis I disorder \[(except for major depression secondary to the PTSD, dysthymia, depression not otherwise specified (NOS) and anxiety disorders (panic disorder, social phobia, generalized anxiety disorder (GAD), specific phobia)\]
* Subject is currently participating in another clinical trial in which she is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month for studies unrelated to PTSD, or 1 month for studies related to PTSD
* Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, central nervous system (CNS) tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of GSK561679.
* Patients who in the investigator's judgment pose a current suicidal or homicidal risk
* DSM-IV substance abuse or dependence within the past 90 days. Subject has a positive test for illegal substances.
* Diagnosis of anorexia nervosa or bulimia in the past year.
* Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody), and/or clinically significant hepatic enzyme elevation including any one of the following enzymes greater than 1.5 times the upper limit of normal (ULN) value (alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total or direct bilirubin \> 1.5 x ULN, unless consistent with presumed or diagnosed Gilbert's disease)
* Subject has taken systemic corticosteroids within 2 weeks of the Randomization Visit
* Treatment with any other psychoactive medication within 2 weeks of Visit 1, including all antidepressants, psychoactive herbal or nutritional treatment (St Johns Wort, SAM-e), lithium, other mood stabilizers, oral antipsychotics, depot antipsychotics within 12 weeks, beta blockers, thioridazine, pimozide, opiates, anxiolytics, and sedatives (with the exception of zolpidem, eszopiclone, and zaleplon). Also any treatment with any medication that the PI judges not acceptable for this study.
* Subject who is likely to require the use of the following medications: Chronic (for more than 2 weeks), regular nonsteroidal anti-inflammatory drugs (NSAID) use. Any use of aspirin (including low dose)
* Subject has taken non-psychoactive (prescription or non-prescription), dietary, or herbal products, with a narrow therapeutic index, that are metabolized via the cytochrome P450 3A4 or 2C9 pathway (warfarin), or transported via OATP1B1 or P-gp, within 2 weeks (or 5 half-lives, whichever is longer) prior to the Randomization Visit.
* Subject has taken other (non-psychoactive) prescription, non-prescription, dietary, or herbal products that are potent inducers or inhibitors of the cytochrome P450 3A4 pathway for 2 weeks (or 5 half lives, whichever is longer) prior to the Randomization Visit.
* Subject has a stool positive for occult blood.
* Pregnancy or lactation
* Subjects who, in the opinion of the investigator, would be non compliant with the visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned hospitalizations during the study).
* Previous treatment with CRF1 receptor antagonist
* Any laboratory abnormality that in the investigator's judgment is considered to be clinically significant (blood pressure, electrocardiogram (ECG), thyroid stimulating hormone (TSH), liver function test (LFT), etc.)
* Patients who are receiving exposure-based psychotherapy that targets PTSD symptoms
* Current or planned litigation or other actions related to secondary gain regarding the traumatic event
* Subject has clinical evidence of, or ECG results indicating any of the following at either screen or Randomization Visit unless repeat ECG shows that the parameter had returned to within normal range by the Randomization Visit:

  1. Corrected QT Interval (QTc) \> 450 msec;
  2. any cardiac condition or ECG evidence that the investigator feels may predispose the subject to ischemia or arrhythmia; or
  3. any ECG abnormality that, in the investigator's judgment, may pose a potential safety concern
B: Inclusion Criteria:

* Age \>18 years.
* Exposure to one or more life-threatening war zone trauma events per the Combat
* Exposure Scale \[78\] and documented by Department of Defense (DD) Form 214, Combat Action Ribbon (Marines), Combat Infantry Badge (Army), or other clear evidence of war zone trauma exposure.
* Eligible for VA health care.
* Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of PTSD derived from the CAPS.
* CAPS total score \>50.
* CAPS Recurrent Distressing Dreams item score \>5 (of maximum score of 8).
* Capable of giving informed consent.
* Stable dose of non-exclusionary (see below) medications for at least 4 weeks prior to randomization.
* Psychotherapeutic treatment stable for at least 4 weeks prior to randomization.
* Good general medical health (see Medical Exclusion Criteria below).
* Female participants must agree to use a reliable form of birth control during the study.

Exclusion Criteria:

Medical:

* Acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension (systolic \<110) or orthostatic hypotension (systolic drop \> 20 millimeters of mercury after two minutes standing or any drop accompanied by dizziness); chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy.
* Untreated sleep apnea, diagnosed by a sleep study, is exclusionary. Treated sleep apnea (e.g., Continuous Positive Airway Pressure, surgery) will not be exclusionary.
* Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist.
* Wounds requiring surgery, embedded shrapnel, and recent surgical amputation do not comprise an exclusion if the individual is otherwise medically eligible.
* Women of childbearing potential with positive pregnancy test or refusal to use effective birth control method, or who are breastfeeding will be excluded.

Psychiatric/Behavioral:

* Meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS), delirium, or any DSM-IV cognitive disorder.
* Exclusion for psychotic disorder is not to be confused with combat trauma-induced reexperiencing symptoms (transient dissociative states or flashbacks), which will not be exclusionary.
* Substance dependence disorder within 3 months or any current substance dependence (stable methadone maintenance will not be exclusionary).
* Current cocaine or stimulant abuse.
* Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others.
* Nonsuicidal depression comorbid with PTSD will not be exclusionary (see below).

Medications/Therapies:

* Current use of prazosin or other alpha-1 antagonist.
* Previous adequate trial of prazosin for PTSD.
* Subjects on trazodone will undergo a 2-week washout period before baseline assessment. (Combining prazosin and trazodone may increase risk of priapism).
* Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) will be not be permitted during the study dose titration period because of increased risk of hypotension in combination with alpha-1 blockers. Following achieving stable dose of study drug, sildenafil, tadalafil, and vardenafil will be permitted at 1/2 the usual starting dose.
* Stimulants or alternative medications with stimulant properties (e.g., ephedra).
* Recent exposure therapy and/or Eye Movement Desensitization and Reprogramming (EMDR). These therapies must have been completed \> 4 weeks before randomization.
* Other psychotropic medications and/or maintenance psychotherapy at a stable dose for at least 4 weeks will not be exclusionary.
C: 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
* 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 intravenous 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;
* Renal impairment, as reflected by a BUN \>20 mg/dL, and/or creatinin clearance of \>1.3 mg/dL;
* Thyroid impairment, as reflected by TSH\> 4.2 mU/L 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) 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
* 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
* 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
D: Inclusion Criteria:

* Primary diagnosis of PTSD
* In grades 6-12
* No change in medication regimen for more than 6 weeks

Exclusion Criteria:

* Diagnosis of ADHD, conduct disorder, thought disorder, or bipolar disorder

Answer: C