Combined Mirtazapine and SSRI Treatment of PTSD: A Placebo-Controlled Trial
|ClinicalTrials.gov Identifier: NCT01178671|
Recruitment Status : Completed
First Posted : August 10, 2010
Results First Posted : February 29, 2016
Last Update Posted : April 8, 2016
The overall goal of this study is to examine the efficacy of the combination of mirtazapine and sertraline in the treatment of posttraumatic stress disorder (PTSD). Sertraline is FDA-approved for PTSD, but it is often not fully effective. The combination of mirtazapine and serotonin reuptake inhibitors like sertraline has appeared highly effective in a related disorder -- depression.
In this study, sixty patients with chronic PTSD will be randomized to treatment with either sertraline + mirtazapine or sertraline + placebo for 12 weeks. Patients who show at least a minimal response after 12 weeks will continue for another 12 weeks on the same treatment.
|Condition or disease||Intervention/treatment||Phase|
|Posttraumatic Stress Disorder||Drug: Mirtazapine Drug: Sertraline Other: Sugar pill||Phase 4|
This double-blind randomized controlled trial was conducted from January 2011 to February 2014. To acquire a diverse sample, outpatients were recruited at an academic medical center and at a private mental health clinic with primarily Spanish-speaking patients. A single team of investigators conducted the trial at both settings. Individuals with chronic PTSD were randomly assigned to 24 weeks of double-blind treatment with sertraline plus mirtazapine or sertraline plus placebo. This study was conducted in compliance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) and the standards established by an Institutional Review Board and by the National Institutes of Health. Informed consent was obtained from participants after the nature of the procedures was explained.
Participants Participants were adults ages 18-75, referred by clinicians or responding to advertisements. After a preliminary telephone screening, eligibility was determined by clinical interview and confirmed by structured interview with trained raters using the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM-IV Axis I Disorders -- Patient Edition. Participants had a principal Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of chronic PTSD of at least moderate severity (CAPS score ≥50), and English or Spanish fluency. Bilingual clinicians treated and assessed individuals with Spanish language preference. Exclusion criteria were significant suicidal ideation; lifetime psychotic disorder, bipolar disorder, organic mental disorder, or seizure disorder; alcohol or substance use disorder in the past 3 months; unstable medical illness; history of traumatic brain injury of greater than moderate severity; pregnancy or nursing; unwillingness to use contraception (for women of childbearing potential); prior nonresponse to sertraline or combined treatment, or intolerance of sertraline or mirtazapine); and psychotropic medication use during the prior 2 weeks (4 weeks for monoamine oxidase inhibitors or fluoxetine), except that zolpidem for insomnia was allowed up to three times per week during the week prior to randomization; psychotherapy initiated within 3 months before randomization. Concomitant psychotropic medications were not permitted during the study.
Randomization and Blinding Randomization used randomly permuted blocks stratified by patient language preference (English vs. Spanish), implemented by the data manager who had no patient contact. Mirtazapine 15 mg capsules or matching placebo capsules were packaged by a pharmacist with no patient contact. Patients were reminded at each visit with the independent evaluator (IE) to not discuss medication or adverse events, and allocations were concealed from all research personnel throughout each patient's participation.
Treatments A single psychiatrist saw each patient for medication management, with an initial visit of 45 minutes and subsequent 30 minute visits weekly for two weeks, biweekly through week 12, then at 4-week intervals. At each visit the psychiatrist assessed clinical improvement and adverse events. Mirtazapine/placebo was initiated at 30 mg (two capsules) at bedtime for four weeks, after which patients without significant adverse events and with persistent PTSD symptoms had dose increased to a maximum of 45 mg/day. Dose could be decreased for intolerable adverse events, to a minimum of 15mg/day. Sertraline was initiated at 25 mg/day for four days, then increased as tolerated to 50 mg/day for the remainder of Week 1, 100 mg/day for Weeks 2-4, 150 mg/d for Weeks 5-6, and then 200 mg/day. Dosage could be decreased as clinically indicated to a minimum of 50 mg/day. Compliance was assessed with patient diaries and pill counts.
Patients who prematurely discontinued study medication were encouraged to return for all assessments through week 24.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Combined Mirtazapine and Selective Serotonin Reuptake Inhibitor (SSRI) Treatment of Post-traumatic Stress Disorder (PTSD)|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||May 2014|
|Actual Study Completion Date :||June 2014|
Experimental: Sertraline and Mirtazapine
Flexible dose of both medications for up to 24 weeks
Mirtazapine capsule, flexible dose of 15-45 mg/day for up to 24 weeks
Other Name: RemeronDrug: Sertraline
Sertraline tablet, flexible dose of 25-200mg/day for up to 24 weeks
Other Name: Zoloft
Active Comparator: Sertraline and Sugar pill
Sertraline and Sugar pill for up to 24 weeks
Sertraline tablet, flexible dose of 25-200mg/day for up to 24 weeks
Other Name: ZoloftOther: Sugar pill
Sugar pill capsule, flexible dose of 1-3 per day, for up to 24 weeks
Other Name: placebo
- PTSD Severity [ Time Frame: up to 24 weeks ]PTSD severity will be measured by the Clinician-Administered Posttraumatic Stress Disorder Scale, from 0 (least severe) to 136 (most severe).
- Time to Discontinuation of Study Treatment [ Time Frame: up to 24 weeks ]
- Alternative Measure of PTSD Severity [ Time Frame: up to 24 weeks ]as measured by the Short Posttraumatic Stress Disorder Rating Interview, which rates severity of PTSD from 0 (least severe) to 32 (most severe)
- PTSD Self-rated Severity [ Time Frame: up to 24 weeks ]as measured by the PTSD Checklist which rates severity of PTSD from 17 (least severe) to 85 (most severe).
- Depression Severity [ Time Frame: up to 24 weeks ]as measured by the 17-item Hamilton Rating Scale for Depression, which rates severity of depression on a scale from 0 (least depression) to 50 (greatest depression).
- Response Status [ Time Frame: up to 24 weeks ]Responders defined by Clinician Administered Posttraumatic Stress Disorder Scale total score decreased by at least 30% compared with baseline and Clinical Global Impression improvement score of =1 or 2 at endpoint
- Remission Status [ Time Frame: up to 24 weeks ]Remitter as defined by Clinician Administered Posttraumatic Stress Disorders Scale total score <20 at endpoint
- Adverse Effects [ Time Frame: up to 24 weeks ]as assessed by Side Effect Checklist
- Sleep Quality [ Time Frame: up to 24 weeks ]as measured by Pittsburgh Sleep Quality Index, which rates severity of impairment in sleep quality from 0 (least impaired) to 21 (most impaired).
- Sexual Functioning [ Time Frame: up to 24 weeks ]as measured by Arizona Sexual Experiences Scale, which rates impairment in sexual functioning from 5 (least impaired) to 30 (most impaired).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01178671
|United States, New York|
|Anxiety Disorders Clinic, New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Principal Investigator:||Franklin Schneier, MD||New York State Psychiatric Institute|