A Safety Study in Participants With Major Depressive Disorder

Long-Term, Open-Label, Safety Study of LY2216684 12 to 18 mg Once Daily as Adjunctive Treatment for Patients With Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment

The primary objective of this study is to evaluate the long-term safety and tolerability of LY2216684 administered once daily (QD) in the adjunctive treatment with a selective serotonin reuptake inhibitor (SSRI) for up to approximately 1 year in participants with major depressive disorder (MDD) who are partial responders to their SSRI treatment.

Inclusion Criteria:

• Adults competent and able to give informed consent
• Women of child-bearing potential may participate but must test negative for pregnancy at the time of study entry; both women/men agree to use a reliable method of birth control
• Participants who are being treated with one of the following selective serotonin reuptake inhibitors (SSRIs): escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine; for at least 6 weeks prior to investigational product dispensing with at least the last 4 weeks at a stable, optimized dose
• Drug and dosage should be within the labeling guidelines for the specific country
• Meet criteria for Major Depressive Disorder (MDD), as defined by the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria
• Meet criteria for partial response, as defined by investigator's opinion that participant has experienced a minimal clinically meaningful improvement with SSRI
• Have a Grid Hamilton Rating Scale for Depression (GRID-HAMD17) total score greater than or equal to 16 at screening
• Have less than or equal to 75 percent improvement on the current SSRI at screening determined by the Massachusetts General Hospital Antidepressant Response Questionnaire (MGH-ATRQ)
• Meet all other inclusion criteria per protocol

Exclusion Criteria:

• Presence of another primary psychiatric illnesses:

  • Have had or currently have any additional ongoing DSM-IV-TR Axis I condition other than major depression within 1 year of screening
  • Have had any anxiety disorder that was considered a primary diagnosis within the past year (including panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and social phobia, but excluding specific phobias)
  • Have a current or previous diagnosis of a bipolar disorder, schizophrenia, or other psychotic disorder
  • Have a history of substance abuse and/or dependence within the past 1 year (drug categories defined by DSM-IV-TR), not including caffeine and nicotine
  • Have a DSM-IV-TR Axis II disorder that, in the judgment of the investigator, would interfere with compliance with protocol

• Unstable medical conditions that contraindicate the use of LY2216684

  • Have any diagnosed medical condition which could be exacerbated by noradrenergic agents including unstable hypertension, unstable heart disease, tachycardia, tachyarrhythmia, narrow-angled glaucoma, urinary hesitation or retention

• Use of excluded concomitant or psychotropic medication other than SSRI

• Have initiated or discontinued hormone therapy within the previous 3 months of prior to enrollment

• History of treatment resistant depression as shown by:

  • Have had 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, transcranial magnetic stimulation, or psychosurgery within the last year

• Meet any other exclusion criteria per protocol