Effectiveness Study of Mirtazapine Combined With Paroxetine in Major Depressive Patients Without Early Improvement
Condition: Major Depression
MeSH terms: Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): mirtazapine; paroxetine 20mg QD
Intervention type(s): Drug; Drug
Intervention description(s): mirtazapine 30mg QD; paroxetine 20mg QD
Other intervention name(s): Remeron; Seroxat
Intervention MeSH terms: Mirtazapine; Paroxetine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: mirtazapine; paroxetine; major depression; early improvement