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Combined Mirtazapine and SSRI Treatment of PTSD: A Placebo-Controlled Trial

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Franklin Schneier, Research Foundation for Mental Hygiene, Inc.
ClinicalTrials.gov Identifier:
NCT01178671
First received: July 29, 2010
Last updated: April 2, 2016
Last verified: April 2016
  Purpose

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 Intervention Phase
Posttraumatic Stress Disorder
Drug: Mirtazapine
Drug: Sertraline
Other: Sugar pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combined Mirtazapine and Selective Serotonin Reuptake Inhibitor (SSRI) Treatment of Post-traumatic Stress Disorder (PTSD)

Resource links provided by NLM:


Further study details as provided by Research Foundation for Mental Hygiene, Inc.:

Primary Outcome Measures:
  • PTSD Severity [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Alternative Measure of PTSD Severity [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Remitter as defined by Clinician Administered Posttraumatic Stress Disorders Scale total score <20 at endpoint

  • Adverse Effects [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]
    as assessed by Side Effect Checklist

  • Sleep Quality [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    as measured by Arizona Sexual Experiences Scale, which rates impairment in sexual functioning from 5 (least impaired) to 30 (most impaired).


Enrollment: 38
Study Start Date: July 2010
Study Completion Date: June 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sertraline and Mirtazapine
Flexible dose of both medications for up to 24 weeks
Drug: Mirtazapine
Mirtazapine capsule, flexible dose of 15-45 mg/day for up to 24 weeks
Other Name: Remeron
Drug: 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
Drug: Sertraline
Sertraline tablet, flexible dose of 25-200mg/day for up to 24 weeks
Other Name: Zoloft
Other: Sugar pill
Sugar pill capsule, flexible dose of 1-3 per day, for up to 24 weeks
Other Name: placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Current primary diagnosis of chronic PTSD
  • Fluent in English or Spanish

Exclusion Criteria:

  • Past or current schizophrenia, schizoaffective disorder, organic mental disorder, bipolar disorder, or antisocial personality disorder.
  • Substance abuse of dependence diagnosis in past 3 months
  • Suicidal ideation or behavior in past 6 months that poses a significant danger.
  • Medical illness that could significant increase risk of sertraline and mirtazapine treatment or assessment of response
  • History of traumatic brain injury of greater than mild severity
  • History of seizure disorder (except febrile seizure in childhood)
  • Currently taking medication which has been effective for patient's PTSD.
  • Inability to tolerate or unwillingness to accept a drug-free period prior to beginning the study for certain psychiatric medications.
  • History of inability to tolerate sertraline or mirtazapine or inadequate response to an adequate trial of combined treatment.
  • Pregnancy, lactation; for women of childbearing potential, not using an effective birth control method.
  • Current cognitive-behavioral therapy. Any psychotherapy initiated within 3 months of beginning this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178671

Locations
United States, New York
Anxiety Disorders Clinic, New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
Research Foundation for Mental Hygiene, Inc.
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Franklin Schneier, MD New York State Psychiatric Institute
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Franklin Schneier, Research Psychiatrist, Research Foundation for Mental Hygiene, Inc.
ClinicalTrials.gov Identifier: NCT01178671     History of Changes
Other Study ID Numbers: R34MH091336 
Study First Received: July 29, 2010
Results First Received: December 8, 2015
Last Updated: April 2, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Research Foundation for Mental Hygiene, Inc.:
PTSD
trauma
anxiety disorder
medication
sertraline
mirtazapine
pharmacotherapy

Additional relevant MeSH terms:
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Sertraline
Mirtazapine
Mianserin
Serotonin Uptake Inhibitors
Antidepressive Agents
Psychotropic Drugs
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Antidepressive Agents, Tricyclic
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Serotonin Antagonists
Antidepressive Agents, Second-Generation

ClinicalTrials.gov processed this record on December 05, 2016