A Study of Adjunctive Treatment to Antidepressant Therapy for Adults With Major Depressive Disorder

A Study of Augmentation With LY2216684 for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment

The primary purpose is to study the efficacy, safety, and tolerability of LY2216684 as an adjunctive treatment for participants with major depressive disorder (MDD), who were identified as partial responders to an adequate course of treatment with a selective serotonin reuptake inhibitor (SSRI) (as defined by history).

This is a 12 week multi-center, double-blind, placebo-controlled study on the efficacy of LY2216684 augmentation of selective serotonin reuptake inhibitors (SSRIs) in participants with MDD who have a partial response to treatment with an SSRI. While remaining on a steady dose of their SSRI treatment at entry into the study, participants will be randomly assigned to adjunctive treatment with LY2216684 or placebo in a 1:1 ratio for 10 weeks of acute treatment.

Inclusion Criteria:

• Meet criteria for major depressive disorder (MDD) as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR criteria)
• Meet criteria for partial response to an adequate course of treatment defined by the investigator's opinion that participant had attained at least minimal improvement on their current Selective serotonin reuptake inhibitor (SSRI) treatment
• Women of child-bearing potential must test negative for pregnancy and agree to use a reliable method of birth control
• Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score greater than or equal 16 to at both study entry and study enrollment
• SSRI treatment for at least 6 weeks at a stable dose for at least 2 weeks prior to study enrollment
• Stated participant preference for augmentation rather than switching antidepressant treatment

Exclusion Criteria:

• Are currently involved in or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug
• Have previously completed or withdrawn from this study or any other study investigating LY2216684
• Have had or currently have any additional ongoing DSM-IV-TR Axis 1 condition other than MDD
• Have had any anxiety disorder preceding the onset of depression that was considered the primary diagnosis within 1 year of study entry
• Have a current or previous diagnosis of Bipolar I or II, psychotic depression, schizophrenia or other psychotic disorder
• Have a history of substance abuse within the past 1 year
• Have an Axis II disorder which, in the judgment of the investigator, would interfere with compliance with the protocol
• Have had a lack of response of the current depressive episode to 2 or more adequate courses of antidepressant therapy at a clinically appropriate dose for at least 4 weeks, or in the judgment of the investigator, the participant has treatment-resistant depression
• Have a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or psychosurgery within the last year
• Women who are pregnant or breastfeeding
• Participants who are judged to be at serious risk for harm to self or others
• Have a serious or unstable medical illness
• Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia or tachyarrhythmia, narrow angle glaucoma, or urinary hesitation or retention
• Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions
• Have a history of any seizure disorder (other than febrile seizures)
• Are taking noradrenergic psychotropic medications, such as tricyclic antidepressants or serotonin norepinephrine reuptake inhibitors (SNRI)
• Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to study entry
• Require psychotropic medication other than sedative/hypnotic medication for sleep
• Are taking or have received treatment with any excluded medication within 7 days prior to study enrollment
• Have a thyroid stimulating hormone (TSH ) level outside the established reference range
• Have initiate or discontinued hormone therapy within the previous 3 months prior to enrollment
• Initiation or change in intensity of psychotherapy or other non-drug therapies within 6 weeks prior to enrollment
• A positive urine drug screen for any substance of abuse at study entry