Effectiveness Study of Mirtazapine Combined With Paroxetine in Major Depressive Patients Without Early Improvement

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Capital Medical University
Sponsor:
Information provided by (Responsible Party):
Gang Wang, Capital Medical University
ClinicalTrials.gov Identifier:
NCT01458626
First received: August 9, 2011
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

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).

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 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. 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.


Condition Intervention Phase
Major Depression
Drug: mirtazapine, paroxetine
Drug: mirtazapine
Drug: paroxetine 20mg QD
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Capital Medical University:

Primary Outcome Measures:
  • Change of 17-item Hamilton Depression Scale (HAMD-17) total score [ Time Frame: From randomization (Week 2) to endpoint(Week 8) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The proportion of subjects at endpoint with HAMD-17≤7 [ Time Frame: From randomization (Week 2) to endpoint(Week 8) ] [ Designated as safety issue: No ]
  • The incidence and nature of overall adverse events [ Time Frame: From enrollment to endpoint (Week 8) ] [ Designated as safety issue: Yes ]
  • The incidence and nature of drug-related adverse events [ Time Frame: From enrollment to endpoint (Week 8) ] [ Designated as safety issue: Yes ]
  • The number of subject withdrawal due to adverse events during double-blind phase [ Time Frame: From randomization (Week 2) to endpoint(Week 8) ] [ Designated as safety issue: No ]

Estimated Enrollment: 540
Study Start Date: April 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: mirtazapine,paroxetine, add-on therapy Drug: mirtazapine, paroxetine
mirtazapine 30mg QD, paroxetine 20mg QD
Other Names:
  • Remeron
  • Seroxat
Active Comparator: mirtazapine monotherapy Drug: mirtazapine
mirtazapine 30mg QD
Other Name: Remeron
Active Comparator: paroxetine monotherapy Drug: paroxetine 20mg QD
paroxetine 20mg QD
Other Name: Seroxat

Detailed Description:

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01458626

Contacts
Contact: Le Xiao, M.D. 86-10-58303186 xiaole373@yahoo.com.cn

Locations
China, Beijing
Beijing Anding Hospital Recruiting
Beijing, Beijing, China, 100088
Contact: Ye Zhao, Master    86-10-58303236    zzzy209@126.com   
Sub-Investigator: 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.         
Sponsors and Collaborators
Capital Medical University
Investigators
Principal Investigator: Gang Wang, M.D., Ph.D Beijing Anding Hospital, Capital Medical University
  More Information

No publications provided

Responsible Party: Gang Wang, Head of Depression Center, Capital Medical University
ClinicalTrials.gov Identifier: NCT01458626     History of Changes
Other Study ID Numbers: MISP # 39888
Study First Received: August 9, 2011
Last Updated: December 11, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Capital Medical University:
mirtazapine
paroxetine
major depression
early improvement

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Paroxetine
Mianserin
Mirtazapine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Antidepressive Agents, Tricyclic
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Serotonin Antagonists

ClinicalTrials.gov processed this record on September 18, 2014