A Placebo-Controlled Study of Mirtazapine for PTSD

NCT00302107 | Completed Phase 4 Results DMC

• 1 other identifier: MHBA-019-05F
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxiety; PTSD

Keywords

Mirtazapine; PTSD; Veterans; antidepressant

Outcome Measures

Primary Outcomes (1)

• Structured Interview of Posttraumatic Stress Disorder (SIP)

  Structured Interview of Posttraumatic Stress Disorder (SIP) is a 17-item clinician-administered scale for PTSD based on Diagnostic Statistical Manual-IV criteria. The SIP has excellent test-retest reliability (0.89; p=.00001), and internal consistency (Conbach α of 0.80). The SIP showed significant correlations with the DTS (r=0.67, p=.0001) and the Impact of Event Scale (r=0.49 p=.0001). Relative to the SCID diagnosis of PTSD, sensitivity, specificity, positive predictive value, negative predictive value, and efficiency values were 100% for all indices using a score of 20 on the SIP. Items are scored on a scale from 0-4 which are summed to yield a total score ranging from 0 to 68 (higher score means more symptomatic or worse outcome). A symptom is counted as positive if it is at least a 2 (moderate).

  Primary outcome is measured at baseline and week 8 (primary endpoint) with primary outcome change scores calculated as week 8 minus baseline score.

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

Mirtazapine

Drug: Mirtazapine

Arm 2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Mirtazapine DRUG

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

Also known as: Remeron

Arm 1

Placebo DRUG

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

Arm 2

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (1)

Tuscaloosa VAMC

Tuscaloosa, Alabama, 35405, United States

Location

Related Publications (1)

• 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.

  PMID: 33084254 DERIVED

Related Links

• VA Medical Center

MeSH Terms

Conditions

Anxiety Disorders; Stress Disorders, Post-Traumatic

Interventions

Mirtazapine

Condition Hierarchy (Ancestors)

Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Small sample of predominantly male combat veterans limits generalizability of findings.

Results Point of Contact

• Title: Lori Davis, MD
• Organization: Tuscaloosa VA Medical Center

lori.davis@va.gov

205-554-2000

Study Officials

• Lori L Davis, MD AB

  Tuscaloosa VAMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2006
• First Posted: March 13, 2006
• Study Start: April 1, 2006
• Primary Completion: May 1, 2011
• Study Completion: June 1, 2012
• Last Updated: November 26, 2014
• Results First Posted: November 26, 2014

Record last verified: 2014-11

Locations

US (1)