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Effectiveness of Methylphenidate in Improving Cognition and Function in Older Adults With Depression

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Helen Lavretsky, MD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00602290
First received: January 23, 2008
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

This study will evaluate the safety and effectiveness of methylphenidate in improving cognition and function in older adults with depression.


Condition Intervention Phase
Depression
Drug: Citalopram
Drug: Methylphenidate (MPH)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Use of Methylphenidate to Improve Clinical Outcomes in Geriatric Depression: A Double-blind Placebo-Controlled Trial of Methylphenidate (Ritalin) Augmentation of Citalopram (Celexa) in Depressed Elderly Patients

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale (HDRS) Maintained Scores at Week 16 [ Time Frame: Maintained response measured at Week 16 ] [ Designated as safety issue: No ]
    The Hamilton Depression Rating Scale (HDRS) is a 24-item depression scale and the total score is summed with a minimum score=0 and maximum score=76. There are no subscales and the higher values represent a worse outcome. Outcomes are measured and defined as follows: 1) Response will be defined as HDRS scores of 10 or less; 2) Sustained response will be defined as maintained response at week 16; 4) Remission will be defined as HDRS scores of 6 or less.


Secondary Outcome Measures:
  • Quality of Life Assessment [ Time Frame: Measured at Baseline and Week 16 ] [ Designated as safety issue: Yes ]

Enrollment: 181
Study Start Date: February 2008
Study Completion Date: February 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 - Citalopram and placebo
Participants will take a combination of citalopram and placebo for 16 weeks
Drug: Citalopram
Citalopram dosage will be 20 to 60 mg a day prior to FDA warning limiting it to 20-40 mg in 2011. Participants will begin taking one 20-mg capsule once per day for 4 weeks, and this dosage may be increased or decreased depending on the participant's response to the medication or side-effect profile. Participants will continue on their assigned dosage of citalopram that will be titrated up after week 4 if clinical global impressions (CGI) scores were > 2 until treatment completion.
Other Name: Celexa
Drug: Placebo
Placebo pills will be taken in combination with the active pills. Participants will initially take 1 capsule twice per day, which will be increased to a maximum of 16 capsules twice per day matching methylphenidate, and 1-3 capsules matching citalopram. After Visit 11, placebo dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
Other Name: placebo
Active Comparator: 2 - Methylphenidate and placebo
Participants will take a combination of methylphenidate and placebo for 16 weeks
Drug: Methylphenidate (MPH)
MPH dosage will be 5 to 40 mg a day. Participants will initially take 1 capsule (2.5 mg) twice per day, which will be increased to a maximum up to 8 x 2.5 mg capsules twice per day. After Visit 11, MPH dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
Other Name: Ritalin
Drug: Placebo
Placebo pills will be taken in combination with the active pills. Participants will initially take 1 capsule twice per day, which will be increased to a maximum of 16 capsules twice per day matching methylphenidate, and 1-3 capsules matching citalopram. After Visit 11, placebo dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
Other Name: placebo
Active Comparator: 3 - Methylphenidate and Citalopram
Participants will take a combination of methylphenidate and citalopram for 16 weeks
Drug: Citalopram
Citalopram dosage will be 20 to 60 mg a day prior to FDA warning limiting it to 20-40 mg in 2011. Participants will begin taking one 20-mg capsule once per day for 4 weeks, and this dosage may be increased or decreased depending on the participant's response to the medication or side-effect profile. Participants will continue on their assigned dosage of citalopram that will be titrated up after week 4 if clinical global impressions (CGI) scores were > 2 until treatment completion.
Other Name: Celexa
Drug: Methylphenidate (MPH)
MPH dosage will be 5 to 40 mg a day. Participants will initially take 1 capsule (2.5 mg) twice per day, which will be increased to a maximum up to 8 x 2.5 mg capsules twice per day. After Visit 11, MPH dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
Other Name: Ritalin

Detailed Description:

Less than 50% of older adults with depression achieve remission and functional recovery in response to first-line antidepressant treatment. Most are left with significant residual symptoms, putting them at risk for illness relapse, frailty, and suicide. Improved understanding of the neurobiology of depression in older adults and mechanisms of treatment response may lead to better clinical management of depression. Methylphenidate (MPH) has long been used in the elderly and the medically ill to provide rapid improvement in depression, apathy, and fatigue. However, its potential beneficial effects on cognitive and functional outcomes in older adults with depression have not been studied. Combining MPH with the serotonergic antidepressant citalopram may result in better clinical outcomes than would using citalopram alone. This study will compare the safety and effectiveness of MPH combined with citalopram, MPH combined with placebo, and citalopram combined with placebo in improving thinking, memory, and speed of recovery in older adults with depression. The study will also evaluate selected dopamine- and serotonin-related gene relationships with mood, cognitive symptoms, and treatment response to MPH and citalopram.

Participation in this double-blind study will last 16 weeks. All potential participants will initially undergo comprehensive medical, neuropsychiatric, and cognitive assessments and genetic testing. These initial assessments will include questionnaires about depressive symptoms, a medical history, an electrocardiogram (ECG), and a blood draw for the genetic testing. Eligible participants will then be randomly assigned to one of three groups: MPH and citalopram, MPH and placebo, or citalopram and placebo. All participants will receive 16 weeks of treatment with their assigned medications. Study visits will occur weekly for the first 6 weeks of treatment and bi-weekly for the remainder of the study. During study visits, participants will undergo vital sign and weight measurements, answer questionnaires, and report any medication side effects. Blood will again be drawn at Visits 4 and 10, and the ECG will be repeated at Visit 10 if any cardiac symptoms occur. Most initial assessments will be repeated on Visit 13, the last study visit. Participants will also be contacted weekly by phone throughout the study to answer questions on how they are feeling and any possible side effects.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
  • Score of 16 or higher on the 24-item Hamilton Depression Rating Scale (HDRS) at study entry
  • Score of 26 or higher on the Mini-Mental State Exam (MMSE)

Exclusion Criteria:

  • History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode
  • Presence of psychotic symptoms
  • Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry
  • Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry
  • Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases
  • Toxic or metabolic abnormalities on laboratory examination
  • Medications taken or medical illnesses present that could account for depression
  • Active heart failure categorized as Class III or greater according to New York Heart Association criteria
  • Heart attack or crescendo angina within the 3 months prior to study entry
  • Symptomatic cardiac arrhythmias or symptomatic, hemodynamically significant mitral or aortic valvular disease
  • Resting heart rate less than 50 beats per minute and a corrected QT (QTc) interval greater than 0.45 seconds
  • Second or third degree atrioventricular block
  • Systolic blood pressure greater than 180 mmHg or less than 90 mmHg and diastolic blood pressure greater than 105 mmHg or less than 50 mmHg at study entry
  • Treated with depot neuroleptic therapy within 6 months prior to study entry
  • Treated with any neuroleptic, antidepressant, anxiolytic medication (other than lorazepam), or over-the-counter CNS-active medications used for treatment of depression (e.g, St. John's Wort, kava-kava, melatonin) within 2 weeks (4 weeks for fluoxetine or monoamine-oxidase inhibitors (MAOIs)) prior to the first administration of study medication
  • Known allergy to citalopram or MPH or history of ineffective treatment with citalopram or MPH for current depressive episode
  • Requires concomitant therapy with any prescription or over-the-counter medications that have potentially dangerous interactions with either citalopram or MPH
  • Requires electroconvulsive therapy (ECT) or received ECT within 3 months prior to study entry
  • Initiated psychotherapy within 3 months prior to study entry or will be initiating or terminating psychotherapy during the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602290

Locations
United States, California
UCLA Semel Institute - Neuropsychiatric Institute (NPI)
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Helen Lavretsky, MD University of California, Los Angeles
  More Information

Publications:
Responsible Party: Helen Lavretsky, MD, Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00602290     History of Changes
Other Study ID Numbers: R01 MH077650, R01MH077650, DATR A4-GPX
Study First Received: January 23, 2008
Results First Received: June 8, 2014
Last Updated: August 28, 2014
Health Authority: United States: Federal Government

Keywords provided by University of California, Los Angeles:
Major Depression
Geriatric Major Unipolar Depression
Executive Cognitive Dysfunction
Elderly
Geriatric
Executive Cognitive Impairment
Quality of Life
Disability
Comorbidity
Medical Burden
Safety
Candidate Genes

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mental Disorders
Mood Disorders
Citalopram
Dexetimide
Methylphenidate
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Cholinergic Agents
Cholinergic Antagonists
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014