Risperidone vs. Olanzapine as add-on Treatment in Treatment Resistant Depression
Condition: Subjects Had Unipolar, Non-psychotic Major Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Atypical neuroleptics may have antidepressant qualities in bipolar depression and in unipolar
      depression. Some data support the use of both Risperidone and Olanzapine, but there are no
      direct comparisons of their relative efficacy and tolerability in treatment resistant
      depression. The current study was designed as a pilot study to examine efficacy and
      tolerability of Olanzapine vs. Risperidone add on to a failed serotonin re-uptake inhibitor
      (SSRI) in depression.
    

Detailed description: 
      Overview of Study Design

      This is a Canadian, multicentre, double blind, comparator trial in 42 patients with TRD. TRD
      is defined as the failure to respond adequately to two successive courses of different
      antidepressants at an adequate dose (at least fluoxetine 20 mg, citalopram 20 mg, paroxetine
      20 mg, sertraline 100 mg, fluvoxamine 150 mg, venlafaxine 225 mg)) for at least 4 weeks. All
      subjects, at entry to the study will be currently not responding to treatment of at least 4
      weeks duration of a serotonin re-uptake inhibitor (SSRI) or a selective nor-epinephrine and
      serotonin re-uptake inhibitor (SNRI). Non-response is defined as a score of 3 ("minimal
      improvement") or worse on the Clinical global Impression of Improvement .

      The objective is to assess the appropriateness of the trial design and to determine sample
      size requirements for future controlled trials. In addition the efficacy and safety of oral
      doses of risperidone (.5-3 mg/day) and olanzapine (2.5-15 mg.day) as add-on therapy to any
      SSRI or SNRI in treatment resistant depression will be evaluated. Subjects meeting the
      screening criteria will enter a 6-week trial with risperidone or olanzapine added on to the
      current SSRI or SNRI therapy.

      A medical/ psychiatric history, HAM-D-29 (only the first 17 items will be used for outcome),
      MADRS and HAM-A will be obtained at screening. At subsequent visits HAM-D, HAM-A, and MADRS
      will be performed and adverse events (spontaneous and using the CASES checklist) and
      concomitant medications will be collected.

      Recruitment:

      Subjects will drawn from two sources:

        1. Outpatients currently attending the clinic at the sites. These subjects will already be
           in treatment or may have been referred from the local communities of the clinics
           involved in this study for consultation. Should these subjects drop out or once they
           have completed the study they will receive the treatment as usual at each site.

        2. Advertisements. Advertisements will be placed in local media (radio, television,
           newspaper) identifying the nature of the study and providing a contact number. These
           advertisements will be approved by the local IRB's prior to posting.
    

Intervention name(s): Risperidone; Olanzapine
Intervention type(s): Drug; Drug
Intervention description(s): Risperidone will commence at 0.5 mg per day in a single daily dose given once in the evening. Clinicians will have the option, at each visit of increasing the risperidone dose to a maximum of 3 mg/day based on subject response and tolerability (please see Titration Recommendations below).; Olanzapine will commence at 2.5 mg per day in a single daily dose given once in the evening. Clinicians will have the option, at each visit, of increasing the olanzapine dose to a maximum of 15 mg/day based on subject response and tolerability.
Intervention MeSH terms: Olanzapine; Risperidone
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: depression; treatment resistant depression; unipolar; non- psychotic major depression; add-on to a serotonin type antidepressants; risperidone; olanzapine; double blind comparison; randomized