A Placebo-Controlled Study of Mirtazapine for PTSD

NCT ID: NCT00302107

Last Updated: 2014-11-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2012-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Anxiety PTSD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm 1

Mirtazapine

Group Type ACTIVE_COMPARATOR

Mirtazapine

Intervention Type DRUG

Mirtazapine initiated at 15mg qhs and titrated in 15mg increments to a maximum of 45 mg qhs as tolerated.

Arm 2

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Look-a-like placebo tablets under double-blind conditions

Interventions

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Mirtazapine

Mirtazapine initiated at 15mg qhs and titrated in 15mg increments to a maximum of 45 mg qhs as tolerated.

Intervention Type DRUG

Placebo

Look-a-like placebo tablets under double-blind conditions

Intervention Type DRUG

Other Intervention Names

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Remeron

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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US Department of Veterans Affairs

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lori L Davis, MD AB

Role: PRINCIPAL_INVESTIGATOR

Tuscaloosa VAMC

Locations

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Tuscaloosa VAMC

Tuscaloosa, Alabama, United States

Site Status

Countries

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United States

References

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Davis LL, Pilkinton P, Lin C, Parker P, Estes S, Bartolucci A. A Randomized, Placebo-Controlled Trial of Mirtazapine for the Treatment of Posttraumatic Stress Disorder in Veterans. J Clin Psychiatry. 2020 Oct 20;81(6):20m13267. doi: 10.4088/JCP.20m13267.

Reference Type DERIVED
PMID: 33084254 (View on PubMed)

Related Links

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Other Identifiers

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MHBA-019-05F

Identifier Type: -

Identifier Source: org_study_id

NCT00449189

Identifier Type: -

Identifier Source: nct_alias