A Study in Relapse Prevention of Treatment-Resistant Depression
Condition: Treatment Resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: Olanzapine and Fluoxetine combination (OFC); Fluoxetine
Intervention description: Open label acute phase: introductory dose for 4 days then 3 milligram (mg) Olanzapine and 25 mg Fluoxetine Combination (3/25), 6/25, 12/25, 6/50, 12/50 or 18/50, oral, daily, for 6-8 weeks.
Open label stabilization phase: 6/25, 12/25, 6/50, 12/50 or 18/50 mg, oral, daily for 16-20 weeks.
Double blind relapse prevention phase: dose determined during stabilization phase at Week 17, oral, daily, for 27 weeks.; 25 or 50 mg/day fixed dosing for 27 weeks
Intervention MeSH terms: Olanzapine; Fluoxetine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 892.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether olanzapine and fluoxetine combination (OFC)
      if used for a long time (47 weeks) makes patients suffering from Treatment Resistant
      Depression stable, determine if OFC is safe when used to treat patients with Treatment
      Resistant Depression for a long time (up to 47 weeks), to determine whether olanzapine and
      fluoxetine combination or fluoxetine alone is better to treat Treatment Resistant Depression
      when treated for a long time (up to 47 weeks) and to assess the quality of life during
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have single or recurrent unipolar Major Depressive Disorder (MDD), without psychotic
             features by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text
             Revision (DSM-IV-TR) clinical assessment, confirmed by the structured clinician
             Interview for DSM-IV Axis 1 disorders (SCID-I).

          -  If female and of childbearing potential, test negative for pregnancy and agree to
             abstain from sexual activity or use a medically accepted means of contraception during
             the study. Use of any oral or injectable contraception must be initiated prior to
             receiving treatment.

          -  Have 17-item Hamilton Depression (HAM-D) score greater than or equal to 18 at
             screening and the day treatment is due to be received for the first time.

          -  Have treatment-resistant depression, as defined by having demonstrated failure to
             achieve satisfactory antidepressant response to adequate separate treatment courses of
             at least 2 different antidepressants within the current episode of MDD.

        Exclusion Criteria:

          -  Have a diagnosis of Parkinson's disease or related disorders.

          -  Have a current or lifetime diagnosis of any of the following according to DSM-IV
             criteria: Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder,
             Delusional Disorder, Psychotic Disorder Not Otherwise Specified, Bipolar Disorder I or
             II, Delirium of any type, Dementia of any type, Amnestic Disorder, any
             Substance-Induced Disorder, or any Psychotic Disorder due to a General Medical
             Condition.

          -  Have current diagnosis of post-partum depression, MDD with atypical features, or MDD
             with a seasonal pattern as defined in the DSM-IV.

          -  Have paranoid, schizoid, schizotypal, antisocial, and borderline personality disorders
             (Axis II) as a comorbid or primary diagnosis, based on DSM-IV criteria.

          -  Have had psychotic symptoms within 1 month prior to Screening or demonstrate psychotic
             features at screening and on the day treatment is due to be assigned for the first
             time as determined by the investigator.

          -  Have DSM-IV substance dependence/abuse or not willing to avoid use of the substance
             (not including dependence on nicotine or caffeine), as defined by the SCID-I, within
             the past 30 days.

          -  Are actively suicidal in the judgment of the investigator.

          -  Have had one or more seizures without a clear and resolved etiology.

          -  Have leukopenia or history of leukopenia without a clear and resolved etiology, or
             known history of agranulocytosis during the participant's lifetime.

          -  Have alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) values
             greater than or equal to 2 times the upper limit of normal (ULN) of the performing
             laboratory or aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase
             (SGOT) values greater than or equal to 2 times the ULN or total bilirubin values
             greater than or equal to 1.5 times the ULN at any time during screening.

          -  Have acute, serious, or unstable medical conditions.

          -  Have any illness such that death is anticipated within 1 year or intensive care unit
             hospitalization for the illness is anticipated within 6 months.

          -  Have elevated prolactin levels at screening.

          -  Have Bazett's corrected QT interval (QTc) greater than 450 milliseconds (male) or
             greater than 470 milliseconds (female) at screening and when treatment is due to be
             received for the first time.

          -  Have received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS)
             treatment within the current episode; have a history of failure to adequate treatment
             courses of ECT or VNS; or will require ECT or VNS at any time during study
             participation.

          -  If receiving psychotherapy, light therapy, or both, are anticipated to require changes
             in frequency/intensity of treatment regimen or to cease treatment regimen over the
             duration of the study. Participants who are not receiving any of these therapies upon
             study entry may not begin any of these therapies during screening, or during any
             treatment phases of the study.

          -  Have received previous treatment with clozapine.

          -  Have used a monoamine oxidase inhibitor (MAOI) within 14 days prior to screening or
             are expected to need MAOI treatment at any time during this study through 5 weeks
             after the participant discontinues from the study.