A Study of Patients With Major Depressive Disorder and Residual Apathy

A Phase 4, 8-week, Double-blind, Randomized Study Comparing Switching to Duloxetine or Escitalopram in Patients With Major Depressive Disorder and Residual Apathy in the Absence of Depressed Mood

The purpose of this study is to provide a comparison of the apathy, depression, and functional outcomes associated with switching to duloxetine or escitalopram in patients who have previously responded to treatment with a selective serotonin reuptake inhibitor (SSRI) for major depressive disorder and who have residual apathy in the absence of depressed mood.

Apathy is reported by up to 30% of patients with major depressive disorder (MDD) and is hypothesized to be a treatment emergent adverse effect associated with selective serotonin reuptake inhibitor medication. While there is currently no consistent method for treating apathy among psychiatrists, it has been proposed that switching MDD patients to antidepressant medications containing both serotonin and norepinephrine, such as duloxetine, may reduce the incidence and severity of apathy in these patients.

Inclusion Criteria:

• Have received treatment with an SSRI (escitalopram, sertraline, paroxetine, or citalopram) for major depressive disorder
• Females of child-bearing potential to test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control
• Apathy Evaluation Scale - Clinician Rated Version (AES-C) total score >30 at screening and randomization.
• Montgomery-Asberg Depression Rating Scale (MADRS) total score ≤15 and Item 1 (apparent sadness) score of <2 at screening and randomization.
• Have a level of understanding sufficient to provide informed consent and to communicate with the investigators, study coordinator, and site personnel.

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device
• Have previously completed or withdrawn from this study or any other study investigating duloxetine.
• Have had previous lack of response to an adequate trial of duloxetine within the past 12 months or escitalopram at any time.
• Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), diagnosis of mania, bipolar disorder, treatment resistant depression or psychosis; or current suicide risk
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision(DSM-IV-TR),substance abuse or dependence within the 6 months
• Presence of an Axis II disorder
• Monoamine oxidase inhibitor (MAOI) treatment within 14 days prior to randomization or the potential need to use an MAOI during the study
• Positive urine drug screen for any substance of abuse or excluded medication.
• Are pregnant or breast-feeding.
• Serious medical illness, requires hospitalization during the study
• Have uncontrolled narrow-angle glaucoma.
• Have acute liver injury or severe cirrhosis
• Abnormal thyroid stimulating hormone (TSH) concentration
• Amphetamines, dopaminergic medications or modafinil within 14 days prior to randomization or potential need to use such medications during the study or within 14 days of discontinuation of study drug.