Lisdexamfetamine Dimesylate in Residual Symptoms and Cognitive Impairment in Major Depressive Disorder.

Inclusion Criteria:

1. Meeting diagnostic criteria for major depression during the present episode of illness, currently with at least mild improvement by report (CGI-I ≥3) but with continuing residual symptoms.
2. A score of ≥10 on MADRS items 1,2,6,7 and 8, (the MADRS Dysphoric Apathy/Retardation factor, Parker et al., 2003) at screening and randomization. These 5 items are: Apparent sadness, Reported sadness, Concentration difficulties, Lassitude, and Inability to feel. A score of ≥3 will be required for at least 2 of these items.
3. A score of 3 or 4 on the Clinical Global Impression of Severity (CGI-S) at screening and randomization.
4. At randomization subjects must have received therapeutic dosages of approved SSRI or SNRI agents for at least 8 weeks, with the last 4 weeks at a constant dosage.
5. Females of Child-bearing Potential (FOCP) must have a negative serum beta Human Chorionic Gonadotropin (B-hCG) pregnancy test at the screening visit and a negative urine pregnancy test at the baseline visit, and agree to use one of the following methods of birth control: oral contraceptives, contraceptive implants, injectable contraceptives, IUDs, double-barrier contraception, sexual abstinence or vasectomized partner(s).

Exclusion Criteria:

1. Treatment within 4 weeks of randomization with any non-SSRI/SNRI antidepressant (trazodone is permitted up to 100 mg at night for sleep); any antipsychotic agent; any mood stabilizer; any standing benzodiazepine regimen other than at low doses for sleep (≤ 1 mg lorazepam HS or the equivalent); or a standing regimen of any other agent that may affect cognitive function (e.g., psychostimulants, including modafinil or R-modafinil).
2. Any current or past psychotic disorder, Bipolar I or II disorder, Current panic disorder, History of ADHD, Antisocial Personality Disorder or Borderline Personality Disorder, Mental retardation or any dementing disorder.
3. Covi Anxiety Scale score greater than Raskin Depression Scale score at Screening, to exclude subjects with more prominent anxiety than depression
4. MADRS Sleep (item 4), or Appetite (item 5) >3 at screening or randomization
5. Initial insomnia at screening that is not adequately controlled by sleep medication (trazodone up to 100 mg HS for sleep and/or ≤ 1 mg lorazepam HS or the equivalent).
6. Medical conditions that might be exacerbated by Vyvanse treatment, such as uncontrolled hypertension or angina; or conditions that would make study findings hard to interpret, such as hyperthyroidism
7. History of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder.
8. Known cardiac structural abnormality or any other condition that may affect cardiac performance
9. Any clinically significant ECG or laboratory abnormality at Screening
10. Current abnormal thyroid function, as defined by abnormal TSH at Screening (Treatment with a stable dose of thyroid medication for at least 3 months is permitted if TSH is normal at screening).
11. Suicide attempt within the past 2 years or a history of any homicidal behavior.
12. MADRS Suicidal thoughts (item 10) >4 at any study visit, or if a patient is considered by the investigator to be at clinical risk of suicide at any time in the course of the study.
13. resting sitting systolic blood pressure >149mmHg or diastolic blood pressure > 95mmHg. Subjects may be on monotherapy with anti-hypertensive medication.
14. documented allergy, hypersensitivity, intolerance, or non-responsivity to methylphenidate or amphetamines.
15. Subject has a history of a substance use disorder (abuse or dependence, as defined by DSM-IV-TR™), with the exception of nicotine dependence, within 6 months prior to screening.
16. Subject has glaucoma
17. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant