Combined Mirtazapine and SSRI Treatment of PTSD: A Placebo-Controlled Trial
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/21/2016 |
| Start Date: | July 2010 |
| End Date: | June 2014 |
Combined Mirtazapine and Selective Serotonin Reuptake Inhibitor (SSRI) Treatment of Post-traumatic Stress Disorder (PTSD)
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.
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.
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.
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.
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.
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