Inclusion Criteria:

Inclusion:

• Either enrolled in the OHSU radiology/oncology clinic or VA palliative care, and living within 120 miles of the Portland VAMC.
• Life-limiting disease is any type of solid or blood cancer.
• Eighteen years of age or older.
• Life expectancy of 1 year or less as reflected by hospice admission or palliative care status. Although exact life expectancy can not be predicted, actively dying patients with estimated life expectancy of < 10 days are unlikely to be enrolled.
• Diagnosis of major depression disorder as determined by the Structured Clinical Interview for Diagnosis (SCID).
• Significant depressive cognitive symptomatology as determined by a MADRS greater than 19.
• Currently taking an SSRI but still depressed enough to meet eligibility criteria or not taking SSRI but depressed enough to start on SSRI.
• Willing and able to give informed consent to participate in this study as demonstrated by the MacArthur Competence Assessment Tool for clinical research.
• Speaks/understands English.
• For patients at home who cannot self-administer medications, has a caregiver who can assist with administering medication.

Exclusion Criteria:

Exclusion:

• Dementia or Delirium as determined by the Short Portable Mental Status Questionnaire (SPMSQ) score of less than 7.
• Diagnosis of delirium as determined by the Confusional Assessment Method (CAM).
• Any of the following Brief Psychiatric Rating Scale (BPRS) items rated 4 -, elated mood, suspiciousness, hallucinations, excitement, distractibility or motor hyperactivity.
• Severe insomnia.
• Severe anxiety.
• Significant suicidal ideation.
• History of current mental disorder in which depressive symptoms occur, but for which psychostimulants are contraindicated (schizophrenia and bipolar disorder will be based on history; active psychotic symptoms on selected BPRS items).
• History of stimulant abuse or other active, severe substance abuse.
• Contraindications to methylphenidate or an SSRI including significant cardiacarrhythmias; uncontrolled, severe hypertension; moderate-severe angina; seizure disorder; severe COPD; use of medications such as Levodopa, monoamine oxidase inhibitors, and lithium; diagnosis of narrow-angle glaucoma; or history of SSRI-induced hyponatremia,.
• Physical symptoms including increased blood pressure (DBP greater than 115, SBP greater than 180), pulse greater than 120, irregular pulse, or chest pain consistant with angina.
• Treatment for depression with a non-SSRI antidepressant including Bupropion and Venlafaxine during protocol.
• Known serum creatinine > 3.0, or severe liver disease as reflected by jaundice or hepatic encephalopathy.
• Unable to swallow pills, however if patient has gastrostomy tube or feeding tube in place the study medicines may be administered by this route. Pills may be poured into food.
• Receiving hospice care in a skilled nursing facility.