Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder

Inclusion criteria

• Subject is able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures.
• Subject is between 18 and 65 years of age.
• Subject has a primary diagnosis of non-psychotic MDD.
• Subject has a MADRS total score >/=24.
• Subject is willing and has an understanding and ability to fully comply with study procedures and restrictions defined in this protocol.
• Subject, who is female, must have a negative serum beta human chorionic gonadotropin (B-HCG) pregnancy test and a negative urine pregnancy test and agrees to comply with any applicable contraceptive requirements of the protocol.
• Subject is able to swallow a capsule.

Exclusion criteria

• Subject whose current episode of MDD has not responded to an adequate treatment regimen with 2 or more approved single antidepressant agents.
• Subject who has a lifetime history of treatment resistant depression, defined as having not responded to adequate treatment with 2 or more treatment regimens.
• Subject has a current co-morbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms.
• Subject has been hospitalized (within the last 12 months) for their current MDD episode.
• Subject has a current or lifetime history of attention-deficit/hyperactivity disorder (ADHD).
• Subject has a first degree relative that has been diagnosed with bipolar I disorder.
• Subject has a recent history (within the last 6 months) of suspected substance abuse or dependence disorder.
• Subject is considered a suicide risk, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation.
• Subject has a concurrent chronic or acute illness or unstable medical condition.
• Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder, serious neurological disease, history of significant head trauma, dementia, cerebrovascular disease, Parkinson's disease, or intracranial lesions.
• Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems.
• Subject has a history of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months prior to the Screening Visit.
• Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
• Subject has glaucoma.
• Subject has any clinically significant ECG or clinical laboratory abnormalities.
• Subject has a history of moderate to severe hypertension.
• Current use of any other medications (including over-the-counter [OTC], herbal or homeopathic preparations) that have central nervous system effects.
• Subject has the potential need to initiate or modify frequency of psychotherapy or to continue or initiate other treatments for depression, outside of those allowed in this protocol.
• Subject has had electroconvulsive therapy (ECT) for the current depressive episode 3 months prior to the Lead-in Baseline Visit.
• The subject has a known or suspected intolerance or hypersensitivity to the investigational product.
• The subject has a known or suspected intolerance, hypersensitivity, or contraindications to their assigned antidepressant treatments (escitalopram oxalate, sertraline HCl, venlafaxine HCl extended release, or duloxetine HCl).
• Subject has a positive urine drug result.
• Subject has a body mass index (BMI) of <18.5 or >40.
• Subject is female and is pregnant or nursing.