A Safety Study in Participants With Major Depressive Disorder

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.


Eligibility Criteria:
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