Effectiveness Study of Mirtazapine Combined With Paroxetine in Major Depressive Patients Without Early Improvement
Information source: Capital Medical University
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depression
Intervention: mirtazapine, paroxetine (Drug); mirtazapine (Drug); paroxetine 20mg QD (Drug)
Phase: Phase 4
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
Le Xiao, M.D., Phone: 86-10-58303186, Email: firstname.lastname@example.org
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
Because most antidepressant treatment guidelines continue to suggest 4~6 weeks of treatment
until nonresponse can be assumed, adherence is required from depressed patients. The ability
to identify the early action of antidepressants allows for earlier initiation of a treatment
adaptation such as alternative or adjunctive treatment. The early identification of non
responders is also important because selection of an antidepressant agent is still primarily
guided by trial. 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. Once a patient demonstrates an appropriate response to an
antidepressant, ongoing treatment is recommended. 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
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. 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
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.
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
The proportion of subjects at endpoint with HAMD-17≤7
The 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
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.
Minimum age: 18 Years.
Maximum age: 60 Years.
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
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: email@example.com
Beijing Anding Hospital, Beijing, Beijing 100088, China; Recruiting
Ye Zhao, Master, Phone: 86-10-58303236, Email: firstname.lastname@example.org
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
Starting date: April 2012
Last updated: December 11, 2012