Effectiveness of Methylphenidate in Improving Cognition and Function in Older Adults With Depression - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00602290

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 IV

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:

MedlinePlus related topics: Depression

Drug Information available for: Benzetimide Dexetimide Citalopram hydrobromide Citalopram Methylphenidate Escitalopram Escitalopram oxalate Methylphenidate hydrochloride

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Hamilton Depression Rating Scale (HDRS) scores [ Time Frame: Measured at Week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Cognitive tests; quality of life, disability, and safety assessments; candidate genes; and drug levels [ Time Frame: Measured at Week 16 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	168
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Participants will take a combination of citalopram and methylphenidate for 16 weeks	Drug: Citalopram Citalopram dosage will be 10 to 40 mg a day. Participants will begin taking one 20-mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of citalopram until treatment completion. Other Name: Celexa Drug: Methylphenidate (MPH) MPH dosage will be 5 to 30 mg a day. Participants will initially take 1 capsule twice per day, which will be increased to a maximum of 12 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
Active Comparator: 2 Participants will take a combination of citalopram and placebo for 16 weeks	Drug: Citalopram Citalopram dosage will be 10 to 40 mg a day. Participants will begin taking one 20-mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of citalopram 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 12 capsules twice per day. After Visit 11, placebo dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.
Active Comparator: 3 Participants will take a combination of methylphenidate and placebo for 16 weeks	Drug: Methylphenidate (MPH) MPH dosage will be 5 to 30 mg a day. Participants will initially take 1 capsule twice per day, which will be increased to a maximum of 12 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 12 capsules twice per day. After Visit 11, placebo dosage will be gradually reduced over 2 weeks until participants are no longer taking any capsules.

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. 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 DSM-IV criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
Score of 20 or higher on the 24-item 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

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

Contacts

Contact: Helen Lavretsky, MD

310-794-4619

hlavrets@ucla.edu

Locations

United States, California
UCLA Semel Institute - Neuropsychiatric Institute (NPI)	Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Helen Lavretsky, MD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Helen Lavretsky, MD

University of California, Los Angeles

More Information

No publications provided

Responsible Party:	Helen Lavretsky, UCLA
ClinicalTrials.gov Identifier:	NCT00602290 History of Changes
Other Study ID Numbers:	R01 MH077650, DATR A4-GPX
Study First Received:	January 23, 2008
Last Updated:	March 23, 2009
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

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
Mood Disorders
Mental Disorders
Citalopram
Dexetimide
Methylphenidate
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors

Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Dopamine Uptake Inhibitors
Dopamine Agents

ClinicalTrials.gov processed this record on February 12, 2012