A Placebo-Controlled Study of Mirtazapine for PTSD
A Placebo-Controlled Study of Mirtazapine for PTSD
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.
Title: A Placebo-Controlled Study of Mirtazapine for PTSD in OIF/OEF Veterans and Veterans
 from all other Southwest Asia Conditions

 Sponsor of the study: VA Merit grant

 Research Setting: Subjects will be recruited from the mental health and primary care
 outpatient clinics and inpatient units. The informed consent process will be conducted in a
 private setting. Rating scales and laboratory procedures will also be performed in a private
 setting.

 Purpose of the study including hypothesis to be tested: The primary objective is to evaluate
 the efficacy and tolerability of mirtazapine (Remeron) in the treatment of PTSD. Primary
 Hypothesis to be tested: Veterans with PTSD will have improvement in their symptomatology
 after 8 weeks of treatment with mirtazapine compared to those treated with placebo.

 Background, including results of relevant research, gaps in the current knowledge. PTSD is a
 common mental illness, afflicting about 3 percent of persons, or 12 million North Americans.
 PTSD is a common consequence of disasters, rape, auto accidents, and violent crime, with
 about half of trauma victims suffering acute symptoms. One fourth of victims of acute PTSD
 progress to develop chronic PTSD. Presently, there are only two medications indicated for
 PTSD (sertraline and paroxetine). Long-term effects of untreated PTSD are serious, including
 depression, alcohol and drug abuse, violence, and suicide. The VA Healthcare System is a
 natural clinical laboratory for study of PTSD, since 14 - 30 % of Vietnam Combat Veterans
 continue to suffer consequences of this disorder. Preliminary clinical data from an open
 studies and one small placebo-controlled study of mirtazapine in the treatment of PTSD
 suggests that mirtazapine is effective and may have a unique pharmacological profile in
 treating PTSD.

 Potential Benefits to the research subject and knowledge to be gained: The actual patient
 participant may benefit from further reduction in underlying psychiatric symptoms. There is
 substantial potential for knowledge about PTSD treatment to be gained by the cumulative data
 gathered in this study that may improve the health care of veterans and nonveterans in the
 future.

 Definition of the population to be studied and justification: The population to be studied is
 outpatient veterans with current PTSD, diagnosed by the use of the MINI. Patients may be
 recruited from mental health, inpatient units or Primary Care Outpatient Clinics, however;
 the majority of the study is intended to be outpatient. The justification for use of a PTSD
 population is that new treatments for PTSD are needed, particularly with combination of
 medications since monotherapy rarely is fully effective.

 Number of subjects: 100 subjects enrolled. Subjects must meet each of the following inclusion
 and exclusion criteria in order to be randomized.

 Subject inclusion criteria:

 -  Diagnosis of PTSD, confirmed by 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). Liver
 function tests (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

 Exit Criteria (One needed to exit):

 -  Completion of the study

 -  Severe and intolerable side effects to mirtazapine/placebo treatment

 -  Acute development of suicidal ideation, homicidal ideation or psychotic symptoms

 -  Symptoms worsen (Score of 7 (very much worse) on CGI-I.

 -  Participant's explicit request to exit the study

 -  The need for additional psychotropic drugs, other than the study drug or adjunctive
 medication as specified in the protocol, for the control of the subjects psychiatric
 symptoms.

 -  The subject becomes pregnant during the course of the study.

 -  Investigator's judgment that it is no longer in the best interest of the patient to
 continue in the study.
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