A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression
Condition: Treatment Resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: Olanzapine; Fluoxetine; Placebo
Intervention description: Administered Orally; Administered Orally; Administered Orally
Intervention MeSH terms: Olanzapine; Fluoxetine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 176.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the efficacy and safety of olanzapine and fluoxetine
      compared to placebo and fluoxetine as treatment for treatment-resistant depression (TRD) in
      Chinese participants.
    

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

          -  Have a total score ≥22 on the 17-item Hamilton Depression Rating Scale (HAM-D17) at
             screening and randomization

          -  Have treatment-resistant depression (TRD), defined as having failed to achieve a
             satisfactory antidepressant response, in the opinion of the investigator, to separate
             treatment courses of at least 2 different antidepressants, other than fluoxetine, of
             adequate dosage and duration (≥6 weeks) within the current major depressive episode

        Exclusion Criteria:

          -  Have a diagnosis of Parkinson's disease or a related disorder

          -  Have a current or lifetime diagnosis of any of the following conditions, according to
             DSM-IV-TR 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 a current diagnosis of post-partum depression or MDD with a seasonal pattern as
             defined in the DSM-IV-TR

          -  Have paranoid, schizoid, schizotypal, antisocial, or borderline personality disorder
             (Axis II) as a comorbid or primary diagnosis, based on DSM-IV-TR criteria

          -  Have DSM-IV-TR substance dependence/abuse or are not willing to avoid use of the
             substance (not including dependence on nicotine or caffeine) within 30 days of
             screening

          -  Are actively suicidal in the judgment of the investigator

          -  Have uncorrected narrow-angle glaucoma

          -  Have had one or more seizures without a clear and resolved etiology

          -  Have leukopenia

          -  Have any acute, serious, or unstable medical conditions

          -  Have an increased serum prolactin concentration at screening

          -  Have a rate-corrected cardiac QT interval, calculated using Bazett's formula (QTc
             Bazett's [Rate-corrected cardiac QT interval on electrocardiogram calculated using
             Bazett's formula(QTcB)]), on Electrocardiogram (ECG) >450 milliseconds (male) or >470
             milliseconds (female) at screening

          -  Have a history of allergic reaction to olanzapine, fluoxetine, or olanzapine in
             combination with fluoxetine

          -  Have had treatment with olanzapine, fluoxetine, or olanzapine in combination with
             fluoxetine withdrawn due to clinically significant and/or intolerable adverse effects
             within 6 months of screening

          -  Have received treatment with remoxipride within 6 months of randomization

          -  Have received treatment with depot antipsychotics within one dosing interval before
             randomization

          -  Have received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS)
             treatment within the current MDD episode, or has a history of failure to respond to
             adequate treatment courses of ECT or VNS, or is expected to require ECT or VNS at any
             time during the study

          -  Have received previous treatment with clozapine

          -  Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of
             screening, or are expected to need MAOI treatment at any time during the study or up
             until 5 weeks after study discontinuation