Methylphenidate for Depressed Cancer Patients Receiving Palliative Care

Condition(s) targeted: Depression; Palliative Care; Cancer; Mental Disorder

Intervention: Methylphenidate + SSRI (Drug); SSRI + placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Department of Veterans Affairs

Official(s) and/or principal investigator(s):
Linda K. Ganzini, MD MPH, Principal Investigator, Affiliation: Portland VA Medical Center

Overall contact:
Robert E Socherman, PhD, Phone: (503) 220-8262, Ext: 54522, Email: robert.socherman@va.gov

The purpose of this study is to determine whether methylphenidate is an effective treatment for depression and to document the safety and tolerability of methylphenidate in combination with an Selective Serotonin Reuptake Inhibitor (SSRI) in SSRI treated, terminally ill, hospice cancer patients. The investigators hypothesize that depressed hospice patients will be more likely to have a 50% reduction in scores on a clinical measure of depression after treatment with Methylphenidate plus an SSRI compared to those patients who are taking a placebo plus and SSRI.

Official title: Methylphenidate for Depressed Cancer Patients in Hospice

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome: 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.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Either enrolled in the OHSU radiology/oncology clinic, VA palliative care, or a

veteran 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 6 months or less as reflected by hospice admission.

- 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.

Exclusion Criteria:

- 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 - mania,

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 ventricular

arrhythmias; uncontrolled, severe hypertension; moderate-severe angina; seizure disorder; severe COPD, use of medications such as Levodopa, monoamine oxidase inhibitors, and lithium; or history of SSRI-induced hyponatremia.

- 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.

- Receiving hospice care in a skilled nursing facility.

Robert E Socherman, PhD, Phone: (503) 220-8262, Ext: 54522, Email: robert.socherman@va.gov

Portland VA Medical Center, Portland, Oregon 97207, United States; Recruiting
Sondra K Long, BA, Phone: 503-273-5315, Ext: 155315, Email: sondra.long@va.gov
Linda K Ganzini, MD MPH, Phone: (503) 220-8262, Ext: 56492, Email: Linda.Ganzini@va.gov
Linda K. Ganzini, MD MPH, Principal Investigator

Starting date: February 2005
Ending date: February 2011
Last updated: September 24, 2009