Study of Mirtazapine for Post-Traumatic Stress Disorder (PTSD) in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans and Veterans From All Other Southwest Conditions

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00302107
First received: March 9, 2006
Last updated: August 14, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Anxiety
PTSD
Drug: Mirtazapine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Study of Mirtazapine for PTSD in OIF/OEF Veterans

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Efficacy of drug versus placebo for treatment of PTSD [ Time Frame: Primary outcome is measured at baseline, week 8, week 16 ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: April 2006
Study Completion Date: June 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
Mirtazapine
Drug: Mirtazapine
Mirtazapine vs. placebo
Placebo Comparator: Arm 2
Placebo
Drug: Placebo
Mirtazapine vs. placebo

  Hide Detailed Description

Detailed Description:

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). 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.
  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00302107

Locations
United States, Alabama
Tuscaloosa VAMC
Tuscaloosa, Alabama, United States, 35405
Sponsors and Collaborators
Investigators
Principal Investigator: Lori Lynne Davis, MD AB Tuscaloosa VAMC
  More Information

Additional Information:
No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00302107     History of Changes
Other Study ID Numbers: MHBA-019-05F
Study First Received: March 9, 2006
Last Updated: August 14, 2013
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Mirtazapine
PTSD
Veterans
antidepressant

Additional relevant MeSH terms:
Anxiety Disorders
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Mental Disorders
Mirtazapine
Mianserin
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Serotonin Antagonists
Serotonin Agents
Antidepressive Agents, Second-Generation

ClinicalTrials.gov processed this record on April 22, 2014