Effectiveness Study of Mirtazapine Combined With Paroxetine in Major Depressive Patients Without Early Improvement
Information source: Capital Medical University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depression
Intervention: mirtazapine (Drug); paroxetine 20mg QD (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Capital Medical University Official(s) and/or principal investigator(s): Gang Wang, M.D., Ph.D, Principal Investigator, Affiliation: Beijing Anding Hospital, Capital Medical University
Overall contact: Le Xiao, M.D., Phone: 86-10-58303186, Email: xiaole373@yahoo.com.cn
Summary
Although treatment guidelines manifest that antidepressant response usually appear with a
delay of several weeks and suggest that treatment should be changed if a partial response
has not occurred after 4~6 week, these beliefs are no longer held by experts, and a new
concept is raised that the first 2 weeks of treatment may be a useful strategy for improving
the management of depression. New evidence indicates that early treatment response can be
predicted with high sensitivity after 2 weeks of treatment in patients with major depressive
disorder (MDD).
Early improvement not only predicted response or remission, but also that lack of
improvement was associated with little chance of response if the treatment strategy remained
unchanged. The criterion of a 20% score reduction has been chosen as an early indicator of
improvement because it can be reliably measured in clinical trials and translates into a
clinically relevant change in the severity of depressive symptoms.
Antidepressants that enhance both serotonergic and noradrenergic neurotransmission may be
more effective than selective serotonin reuptake inhibitors (SSRIs) for acute-phase therapy
of major depressive disorder. As a noradrenergic and specific serotonergic antidepressant,
the antidepressive mechanism of mirtazapine is quite superior to SSRI and in particular has
been suggested to have a faster onset of action than SSRIs in MDD patients.
The aim of this study is to provide physicians with further information regarding early
improvement and the effectiveness of mirtazapine combined with a SSRI antidepressant therapy
in nonresponders.
Clinical Details
Official title: A Double-blind, Active-controlled, Randomized Study Comparing Mirtazapine Combined With Paroxetine or Paroxetine Monotherapy in Patients With Major Depressive Patients Without Early Improvement in the First 2 Weeks
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Change of 17-item Hamilton Depression Scale (HAMD-17) total score
Secondary outcome: The proportion of subjects at endpoint with HAMD-17≤7The incidence and nature of overall adverse events The incidence and nature of drug-related adverse events The number of subject withdrawal due to adverse events during double-blind phase
Detailed description:
Mirtazapine has significant advantages in response and remission rates compared with various
SSRIs in double-blind treatment. Mirtazapine combined with SSRIs or venlafaxine was also
found to be one of the more effective and successful strategy for nonresponders in MDD. The
investigators hypothesized that mirtazapine as adjunctive treatment to paroxetine can boost
the onset time and also can improve the antidepression action of SSRIs in patients without
early improvement.
The aim of this study is to provide physicians with further information regarding early
improvement and mirtazapine combined with a SSRI antidepressant therapy in nonresponders, by
providing a comparison of depressive symptoms outcomes associated with adjunctive
mirtazapine or mono- paroxetine in MDD patients who have previously been treated with
paroxetine for 2 weeks and who have not attained improvement. Paroxetine has been chosen as
a comparator because it is a widely-used and relatively well-tolerated SSRI antidepressant.
The study is designed as a multi-center, randomized, double-blind, active-controlled trial
in subjects with MDD.
Patients will be male or female, 18 to 60 years of age, inclusive, outpatient or inpatient
status, with diagnosis of major depressive episode (single or recurrent) by DSM-IV. The
patients should also have HAMD-17 total score ≥ 20,a HAMD-17 Item 1(depressed mood) score ≥
2 at enrollment in open-label preliminary phase.
It will consist of 2 phases. An open-label preliminary phase lasts for 2 weeks, during which
paroxetine is titrated up to 20mg/day (Day 5). At Week 2, patients will be evaluated by
HAMD-17. The patients who have achieved early improvement (the decrease of HAMD-17 total
score ≥ 20%) will be discontinued. The patients who have not achieved early improvement (the
decrease of HAMD-17 total score < 20%), will be randomized into three treatment arms
[1. Mirtazapine (30mg/d); 2. Paroxetine (20mg/d); 3. Mirtazapine (30mg/d) +Paroxetine(20mg/d)].
In double-blind treatment phase (consist of 6 weeks), patients will be evaluated at Week 3,
4, 6 and 8.
Primary efficacy measure will be assessed based on the decrease of HAMD-17 from
randomization (Week 2) to endpoint (Week 8). CGI-I and CGI-S will be used as secondary
efficacy measures throughout this phase.
The safety in this study will be assessed by adverse event reporting, clinical laboratory
measurements and physical examinations.
Up to 540 patients will enter into Open-label Phase in order to yield approximately 200
evaluable patients in Randomization Phase.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Has given written informed consent.
2. Male or female outpatients aged at least 18 years and not more than 60 years.
3. Has a diagnosis of major depressive disorder by Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV) criteria.
4. HAMD-17 ≥ 20 and HAMD-17 Item 1(depressed mood) score ≥2 at enrolment in open-label
preliminary phase.
Exclusion Criteria:
1. Currently enrolled in, or discontinued within the last 30 days from, a clinical trial
involving an off-label use of an investigational drug.
2. Current Axis I primary psychiatric diagnosis other than major depressive disorder.
3. Organic mental disease, including mental retardation.
4. History of clinically significant disease, including any cardiovascular, hepatic,
renal, respiratory, hematologic, endocrinologic, or neurologic disease, or clinically
significant laboratory abnormality that is not stabilized or is anticipated to
require treatment during the study.
5. Subjects receiving an investigational agent (including different formulation and
generic agents of investigational drug) in the previous 3 months prior to screening.
6. Women in pregnancy or lactation, or female of child bearing potential without
appropriate birth control measures.
7. Use of antipsychotics or mood stabilizers within 5 days prior to screening.
8. Has received depot antipsychotic medication within one cycle prior to screening.
9. Known allergy or lack of response to mirtazapine.
10. Has received ECT or MECT within 3 months prior to screening.
11. Significant risk of suicidal and/or self-harm behaviors.
Locations and Contacts
Le Xiao, M.D., Phone: 86-10-58303186, Email: xiaole373@yahoo.com.cn
Beijing Anding Hospital, Beijing, Beijing 100088, China; Recruiting Ye Zhao, Master, Phone: 86-10-58303236, Email: zzzy209@126.com Le Xiao, M.D., Sub-Investigator Yuan Feng, M.D., Sub-Investigator Ling Zhang, M.D., Sub-Investigator Wei Wang, M.D., Sub-Investigator Xue Wang, M.D., Sub-Investigator Xiaohong Li, M.D., Sub-Investigator
Additional Information
Starting date: April 2012
Last updated: July 27, 2015
|