• The MADRS will measure change in depression over the 18-day study. A subscale of the HADS will measure improvement in depression. To assess the safety & tolerability of methylphenidate a review of possible side effects will be administered at each visit. [ Time Frame: 18 Days ] [ Designated as safety issue: No ]
  

• The degree to which depression improvement is mediated by pain (WBP Inventory). The measure of quality of life at the end of life will help examine whether methylphenidate treatment results in improvements in the various domains of quality of life. [ Time Frame: 18 days ] [ Designated as safety issue: No ]
  

Background: Major depressive disorder can be diagnosed in between 5% and 26% of terminally ill patients. This disorder causes suffering, and is associated with suicidality, increased pain, and increased caregiver burden and caregiver depression. Treatment of depression in cancer patients in hospice and palliative care is complicated by shortened life expectancy. Currently-approved antidepressants take several weeks to be effective. Methylphenidate has been reported in case series and very small randomized trials in patients without cancer as a rapidly effective treatment for depression in medically ill patients. There are no randomized controlled trials to test this agent in terminally ill cancer patients.

Objectives: (1) To determine the effectiveness and safety of methylphenidate for depression treatment in cancer patients receiving hospice and palliative care, (2) to explore whether successful treatment of depression is associated with improved quality of life, and (3) to explore whether effective treatment of depression influences caregiver depression and caregiver burden.

Methods: We will conduct an 18-day randomized, double-blind, fixed-dose (10 mg bid), placebo-controlled clinical trial of methylphenidate for depression in eligible veteran and non-veteran cancer patients with advanced cancer in the following settings: inpatient and outpatient hospice, inpatient and outpatient palliative care, and inpatient and outpatient cancer clinics. We will determine whether improvement in depression is mediated by decreased pain and document the safety and tolerability of methylphenidate in these patients. We will explore whether improvement in depression results in improved quality of life for these patients, and decreases caregiver depression and burden. Eligible patients who answer yes to the question "are you sad or depressed" will be invited to participate. They will complete measures of depression [Structured Clinical Interview for Diagnosis (SCID), Montgomery-Asberg Depression Rating Scale (MADRS) as primary outcome, Hospital Anxiety and Depression Scale as secondary outcome)], quality of life, pain, and cognition at baseline. MADRS scores must be greater than 19 and SCID positive for depression at study entry. Subjects will be randomized to either methylphenidate plus an SSRI, or placebo plus an SSRI. Subjects may continue any previously prescribed SSRI, or will be prescribed citalopram if untreated. Participants will be evaluated with the same measures as baseline on days 3, 6, 12 and 18 of the study. In an open label portion of the study, methylphenidate-treated patients whose depression has improved will be followed up to 2 months. Cox proportional hazard analysis will be used to analyze the primary outcome. An estimated 104 subjects will be entered over five years. Caregivers will complete measures of depression and caregiver burden at days 0 and 18.

Findings: As of 9/16/2009, 46 subjects have been entered. Because enrollment was lower than anticipated, the study was opened in 2006 to cancer patients receiving palliative care, not just hospice patients. In addition to changing enrollment criteria, the study added all oncology clinics at OHSU as additional recruitment sites. The study was suspended for four months secondary to toxicity concerns but is now reopened after review by the OHSU Oregon Cancer Center Data Safety Monitoring Board.

Status: Project work is ongoing. Impact: This study will determine the effectiveness of methylphenidate for treatment of depression in cancer patients receiving palliative care.