Clinical trial NCT00129467: Methylphenidate for Depressed Cancer Patients Receiving Palliative Care
Official title: Methylphenidate for Depressed Cancer Patients in Hospice
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Palliative Care
Cancer
Mental Disorder
Keywords: Depression
Hospice Care
Antidepressive Agents
Methylphenidate
Central Nervous System Stimulant
Pain
Caregiver Burden
Cancer
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Oregon Health and Science University
First posted: 2005-08-11
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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 and palliative care cancer patients. The investigators hypothesize that depressed hospice and palliative care 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 an SSRI.

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 \[Structured Clinical Interview for Diagnosis (SCID), Montgomery-Asberg Depression Rating Scale (MADRS) as primary outcome, Hospital Anxiety and Depression Scale (HADS) as secondary outcome\], 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.

Eligibility criteria: 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 cardiac arrhythmias; 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 consistent 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.

Primary outcomes:
measure: Days to Remission of Depression
timeFrame: 18 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
Study officials:
affiliation: VA Portland Health Care System, Portland, OR
name: Linda K. Ganzini, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: