Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Placebo-Controlled Study of Mirtazapine for PTSD in OIF/OEF Veterans
Brief Summary: Objective: To study the efficacy and tolerability of mirtazapine (Remeron) in the treatment of PTSD.

Research Design: This is an 8-week randomized, double-blind, placebo-controlled treatment trial of mirtazapine for the treatment of PTSD as defined on the Clinical Assessment of PTSD Scale (CAPS).

Methodology: After signing an informed consent and meeting all inclusion/exclusion criteria, the patient is randomized to either mirtazapine versus placebo for 8-week duration. During the study a pharmacist maintains the randomization log and verifies the order for the placebo or mirtazapine in look-a-like tablets. Patients' symptoms, side effects and compliance are assessed bi-weekly. Based on symptomology and occurrence of side effects, the investigator increases the medication in 15 mg increments, as tolerated, until a maximum therapeutic benefit is achieved, not to exceed 45 mg/day. The dosing is at bedtime. Compliance is assessed by bi-weekly pill count at week 4 and week 8. Patients are given supportive clinical management during the clinic visits. An investigator is available by telephone 24 hrs a day in case of emergency. Patients may be seen more often if needed. Efficacy will be measured by the following assessment scales: Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (Ham-A), Clinical Global Impression Severity of Illness (CGI-s), Clinical Global Impression of Improvement (CGI-I), Global Assessment of Functioning (GAF), CAPS, Treatment Outcome PTSD rating scale (TOP-8), and Davidson Trauma Scale (DTS).

Clinical Significance: Mirtazapine has shown promise in treating PTSD in an open label trial. This study is the next step in proving mirtazapine's efficacy in treatment of PTSD.


Options:
A: 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.
B: Inclusion Criteria:

* Male or female outpatients 18-64 years of age with a primary diagnosis of PTSD as defined by DSM-IV criteria with associated sleep disturbance

Exclusion Criteria:

* Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception.
* Concurrent use of other psychotropic medications, other than antidepressants at stable dose for at least 4 weeks prior to randomization
* Serious medical illness or instability
* Seizure disorders with the exception of a history of febrile seizures if they occurred during childhood
* Concurrent psychotherapy initiated within one month of randomization or ongoing psychotherapy of any duration directed specifically toward treatment of PTSD and/or sleep disturbance
* Diagnosis of schizophrenia, mental retardation, OCD, organic medical disorders or bipolar disorder, eating disorders in the past 6 months, alcohol or substance abuse in the past 3 months, or dependence within the past 6 months.
* Patients with significant suicidal ideation or who have enacted suicidal behaviors within 6 months prior to intake
C: Inclusion Criteria:

* Participants must satisfy DSM-IV diagnostic criteria for chronic PTSD
* Evidence of PTSD disease base upon one or more of the following:
* Mild or greater depression on the Beck Depression Inventory -II (BDI-II, score\> 12).
* May have other symptom co-morbid with PTSD (e.g., anxiety or somatic pain)
* Ability to comprehend and satisfactorily comply with protocol required and signed written informed consent prior to entering study procedure
* May be in psychotherapy if initiated at least three months prior to the screening visit. Subject must not discontinue or otherwise alter therapy during the study.
* Subject may not have taken any psychopharmacological medications within 7 days prior to Baseline visit.
* Negative urine pregnancy test at screening visit and for the duration of the study for women of childbearing potential.

Exclusion Criteria:

* Patients with a concurrent DSM-IV Axis I diagnosis in any of the following categories:

  1. Delirium, Dementia, Amnestic and other Cognitive disorders
  2. Lifetime Schizophrenia and other Psychotic Disorders
  3. lifetime Bipolar I Disorder
  4. Bipolar-II Disorder with an episode of hypomania within the last year
  5. Alcohol or Substance Dependence or Abuse (excluding nicotine) in one month prior to the Screening Visit
  6. Any other concurrent Axis I Disorder (including Major Depressive Disorder) must be secondary to the primary diagnosis of PTSD.
* Decisional incapacity (dementia)
* Use of centrally acting medications that potentially have an effect on biological expression
* Chronic pain levels requiring use of any opiate medications
* Known exposure to chemicals of physical traumas that cause neuropsychiatric sequelae
* Past chronic PTSD
* History of 2 or more treatment failures on SSRIs given primarily for the treatment of PTSD, in adequate does at the Investigator's opinion, for at least 8 weeks
* History of intolerance or hypersensitivity to SSRI's
* History of seizures
* Significant risk of committing suicide, or are homicidal or violent and in the Investigator's opinion in significant imminent risk of hurting others
* Treated with depot-neuroleptic within 3 months or MAO inhibitors within 30 day prior to Baseline visit
* Received ECT within 3 months prior to Screening visit
* Pregnant or nursing, women of childbearing potential who are sexually active and do not use adequate contraception, or who are judged to be unreliable in their use of contraception
* Positive urine drug screen, unless proven to be prescribed for a short-term course of treatment. Drug screen must be repeated at least 7 days after the last dose of prescription medication containing narcotics
* A medical condition, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial
* Requiring concomitant treatment with any psychotropic drug (except zolpidem for sleep)
* Plans to initiate or terminate any form of psychotherapy or behavior therapy during the study
* Receiving disability payments (\> 50 % service connections or total Social Security) or who are involved in litigation for PTSD or other psychiatric illnesses.
* Unable to speak, read, and understand English or are judged by the investigator to be unable or unlikely to follow the study protocol and complete all scheduled visits
D: Inclusion Criteria:

* Diagnosis of PTSD, confirmed by Mini-International Neuropsychiatric Interview (MINI) and CAPS
* Age 19 or older
* No substance abuse/dependence for the previous 4 weeks (except for nicotine and caffeine)
* Free of psychotropic medication for 2 weeks (except 4 weeks for fluoxetine)
* Clinically normal physical and laboratory examination (lab profile listed below). LFTs up to 2.5 times the normal limit will be allowed.
* Women of childbearing potential must be using medically approved methods of birth control (such as a condom, birth control pill, Depo-Provera, or diaphragm with spermicides)
* Signed informed consent
* Male or female, any race or ethnic origin

Exclusion Criteria:

* Lifetime history of bipolar I, psychotic, or cognitive disorders
* Actively suicidal, homicidal, or psychotic
* History of sensitivity to mirtazapine
* Unstable general medical conditions
* Score 6 on Question #10 of MADRS regarding suicidal ideation
* Women who are pregnant, planning to become pregnant or breastfeed during the study

Answer: D