A Study of Olanzapine and Fluoxetine for Treatment-resistant Depression

Lilly

Status and phase: Terminated; Phase 3

Conditions: Treatment Resistant Depression

Treatments: Drug: Fluoxetine; Drug: Olanzapine; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01687478

F1D-CR-HGNB (Other Identifier)

13702

Details and patient eligibility

About

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.

Enrollment: 176 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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176 participants in 2 patient groups, including a placebo group

Olanzapine + Fluoxetine

Experimental group

Description:

Olanzapine starting dose is 5 milligram (mg) (1 tablet). May titrate up to 10 mg (2 tablets), or 15 mg (3 tablets) administered once daily by mouth for 8 weeks. Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.

Treatment:

Drug: Fluoxetine

Drug: Olanzapine

Placebo + Fluoxetine

Placebo Comparator group

Description:

Placebo matches the Olanzapine tablet for blinding. Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.

Treatment:

Drug: Placebo

Drug: Fluoxetine