AnxietyPhase 4NCT00302107
A Placebo-Controlled Study of Mirtazapine for PTSD
A Phase 4 study testing Mirtazapine in people with Anxiety and PTSD, run by US Department of Veterans Affairs at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 19 to 65 yearsHealthy volunteers can take part
- What is being tested?
- Mirtazapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Jun 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Placebo-Controlled Study of Mirtazapine for PTSD in OIF/OEF Veterans
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).
Read more
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.
Read the detailed description
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.
- Being tested
- Mirtazapine, Placebo
- Keywords
- Mirtazapine, PTSD, Veterans, antidepressant
- Medical subject headings
- Anxiety Disorders, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirtazapineDrug
Also called Remeron
Mirtazapine initiated at 15mg qhs and titrated in 15mg increments to a maximum of 45 mg qhs as tolerated.
PlaceboDrug
Look-a-like placebo tablets under double-blind conditions
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | Mirtazapine Receives: Drug: Mirtazapine |
| Arm 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Primary outcome is measured at baseline and week 8 (primary endpoint) with primary outcome change scores calculated as week 8 minus baseline score.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2006 (estimated)
- Study startApr 2006
- Primary completionMay 2011
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnxietyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Lori L Davis, MD AB, Principal investigator, Tuscaloosa VAMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00302107
- Sponsor's protocol ID
- MHBA-019-05F
- Status last verified
- Nov 2014
- First submitted
- 9 Mar 2006
- Last updated
- 26 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33084254
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Study of Mirtazapine for PTSD in OIF/OEF Veterans
- ClinicalTrials.gov ID
- NCT00302107
- Acronym / sponsor ID
- MHBA-019-05F
- Keywords
- Mirtazapine, PTSD, Veterans, antidepressant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Apr 2006
- Primary completion
- May 2011 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 13 Mar 2006 (estimated)
- Results
- Posted 26 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: MirtazapineMirtazapine |
| Arm 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MirtazapineAlso: RemeronMirtazapine initiated at 15mg qhs and titrated in 15mg increments to a maximum of 45 mg qhs as tolerated. | Drug | Arm 1 |
| PlaceboLook-a-like placebo tablets under double-blind conditions | Drug | Arm 2 |
Primary outcome
Structured Interview of Posttraumatic Stress Disorder (SIP)
Time frame: Primary outcome is measured at baseline and week 8 (primary endpoint) with primary outcome change scores calculated as week 8 minus baseline score.
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33084254Davis 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.
- VA Medical CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lori L Davis, MD AB principal investigator
Tuscaloosa VAMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mirtazapine in people with Anxiety and PTSD, run by US Department of Veterans Affairs at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Structured Interview of Posttraumatic Stress Disorder (SIP) (time frame: Primary outcome is measured at baseline and week 8 (primary endpoint) with primary outcome change scores calculated as week 8 minus baseline score.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00302107, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2014.