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 toparticipate in the study.
• Subject is between 18 and 65 years of age.
• Subject has a primary diagnosis of non-psychotic MDD (single or recurrent).
• Subject has a MADRS total score 24.
• Subject who is female, must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test and a negative urine pregnancy test at the and agrees to complywith 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 treatmentregimen with 2 or more approved single antidepressant agents.
• Subject who has a lifetime history of treatment resistant depression.
• Subject has a current co-morbid psychiatric disorder. Excluded are: any significantAxis II disorder (including borderline personality disorder), any bipolar disorder,any current or lifetime psychosis, post traumatic stress disorder, obsessivecompulsive disorder, any pervasive development disorder, anorexia nervosa and bulimianervosa.
• Subject has been hospitalized (within the last 12 months) for their current MDDepisode.
• 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 abuseor dependence disorder
• Subject is considered a suicide risk in the opinion of the Investigator, haspreviously made a suicide attempt within the past 3 years, or is currentlydemonstrating 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 ticdisorder, 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, advancedarteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythmabnormalities, coronary artery disease, or other serious cardiac problems.
• Subject has a history of thyroid disorder that has not been stabilized on thyroidmedication 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 a history of moderate to severe hypertension.
• Current use of any other medications (including over-the-counter [OTC], herbal orhomeopathic preparations) that have central nervous system effects.
• Subject has had electroconvulsive therapy (ECT) for the current depressive episode 3months prior.
• The subject has a known or suspected intolerance, hypersensitivity, orcontraindications 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.