Methylphenidate for Depressed Cancer Patients Receiving Palliative Care

NCT00129467 | Completed Results DMC

• 4 other identifiers: IIR 03-1940115310-0603CPC-04115-LX
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Palliative Care; Cancer; Mental Disorder

Keywords

Depression; Hospice Care; Antidepressive Agents; Methylphenidate; Central Nervous System Stimulant; Pain; Caregiver Burden; Cancer

Outcome Measures

Primary Outcomes (1)

• Days to Remission of Depression

  Days to a 50% or greater reduction in initial Montgomery-Asberg Depression Rating Scale (MADRS) score.

  18 Days

Study Arms (2)

methylphenidate + SSRI

EXPERIMENTAL

During the 18-day blind treatment period, subjects will be prescribed methylphenidate 5-10 mg twice per day and selective serotonin reuptake inhibitor (SSRI). Subjects already receiving a SSRI when they begin the study, will continue on the recommended dose of that SSRI; subjects not receiving a SSRI will be prescribed 10-20 mg per day Citalopram. Subjects who respond to methylphenidate treatment will have the option of continuing on methylphenidate, up to 15 mg bid, and an antidepressant in the 6 week open label portion of the study.

Drug: Methylphenidate; Drug: Selective Serotonin Uptake Inhibitor (SSRI)

Placebo + SSRI

PLACEBO COMPARATOR

During the 18-day blind treatment period, subjects will be prescribed placebo 1-2 capsules twice per day and selective serotonin reuptake inhibitor (SSRI). Subjects already receiving a SSRI when they begin the study, will continue on the recommended dose of that SSRI; subjects not receiving a SSRI will be prescribed 10-20 mg per day Citalopram.

Drug: Placebo; Drug: Selective Serotonin Uptake Inhibitor (SSRI)

Interventions

Methylphenidate DRUG

Subjects will take methylphenidate 5 mg twice daily (bid) for 3 days, then 10 mg bid for the remainder of the study. Should a subject have a 50% decrease in their depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS) at the initial dose of methylphenidate, they will be maintained at that lower dose as long as their MADRS score remains reduced by 50%. During the 18-day blinded treatment period the total daily dose will not exceed 20 mg. If subjects have side effects when increasing to 10 mg bid, they will drop back to 5 mg bid. If the participant develops psychosis or cardiac events, they will be discontinued from methylphenidate. Subjects who receive methylphenidate and respond with a 50% reduction in MADRS score will have the option to continue in the open label portion of the study for up to 6 weeks. For patients taking methylphenidate 10 mg bid whose MADRS score is \> 10 at day 18, the dose may be increased to 15 mg bid.

Also known as: Ritalin

methylphenidate + SSRI

Placebo DRUG

Subjects assigned to placebo will receive 1 capsule of placebo twice per day (bid) for 3 days and then 2 capsules bid for the remainder of the study. Should a subject have a 50% decrease in their depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS) at the initial dose of placebo, they will be maintained at that lower dose as long as their MADRS score remains reduced by 50%. If subjects have side effects when increasing the dose to 2 capsules bid, they will drop back to 1 capsule bid. If the participant develops psychosis or cardiac events, they will be discontinued from the intervention.

Placebo + SSRI

Selective Serotonin Uptake Inhibitor (SSRI) DRUG

Each subject will be treated with a SSRI. Patients who are taking an SSRI at the time of enrollment will continue on the same medication during the 18-day blind treatment period. The prescribed dose will only be adjusted if it is more than the highest dose in the recommended range (fluoxetine to 40 mg, paroxetine to 40 mg, citalopram to 40 mg, sertraline to 150 mg). Patients who are not on a SSRI at the time of enrollment will be prescribed citalopram 10 mg per day for 2 weeks, then 20 mg per day. A subject's SSRI may be discontinued if the subject experiences moderate to severe side effects likely attributable to a SSRI. If subjects experience similar symptoms when increasing their citalopram dose to 20 mg per day, they will drop back to 10 mg per day. During the open label extension, the SSRI may be increased, decreased, or changed to a different SSRI or other antidepressant with the exception of venlafaxine and bupropion

Also known as: Celexa

Placebo + SSRI; methylphenidate + SSRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Vita G, Compri B, Matcham F, Barbui C, Ostuzzi G. Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev. 2023 Mar 31;3(3):CD011006. doi: 10.1002/14651858.CD011006.pub4.

  PMID: 36999619 DERIVED

MeSH Terms

Conditions

Depression; Neoplasms; Mental Disorders; Pain; Caregiver Burden

Interventions

Methylphenidate; Selective Serotonin Reuptake Inhibitors; Citalopram

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Stress, Psychological

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Frequency threshold for reporting nonserious adverse events was not determined at the start of the study, but a % was required to be entered in order to complete the adverse event module

Results Point of Contact

• Title: Dr. Linda Ganzini
• Organization: Portland Veterans Affairs Medical Center

linda.ganzini@va.gov

(503) 220-8262

Study Officials

• Linda K. Ganzini, MD MPH

  VA Portland Health Care System, Portland, OR

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2005
• First Posted: August 11, 2005
• Study Start: February 1, 2005
• Primary Completion: September 1, 2009
• Study Completion: December 1, 2010
• Last Updated: April 24, 2015
• Results First Posted: February 12, 2014

Record last verified: 2013-08

Locations

US (1)