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

NCT ID: NCT00602290

Last Updated: 2018-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2013-02-28

Brief Summary

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

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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1 - Citalopram and placebo

Participants will take a combination of citalopram and placebo for 16 weeks

Group Type: ACTIVE_COMPARATOR

Citalopram

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

2 - Methylphenidate and placebo

Participants will take a combination of methylphenidate and placebo for 16 weeks

Group Type: ACTIVE_COMPARATOR

Methylphenidate (MPH)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

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.

3 - Methylphenidate and Citalopram

Participants will take a combination of methylphenidate and citalopram for 16 weeks

Group Type: ACTIVE_COMPARATOR

Citalopram

Intervention Type: DRUG

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.

Methylphenidate (MPH)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Celexa; Ritalin

Eligibility 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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Helen Lavretsky, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Helen Lavretsky, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

UCLA Semel Institute - Neuropsychiatric Institute (NPI)

Los Angeles, California, United States

Countries

United States

References

Schneider B, Ercoli L, Siddarth P, Lavretsky H. Vascular burden and cognitive functioning in depressed older adults. Am J Geriatr Psychiatry. 2012 Aug;20(8):673-81. doi: 10.1097/JGP.0b013e31822ccd64.

Reference Type: RESULT

PMID: 21857219 (View on PubMed)

Eyre HA, Eskin A, Nelson SF, St Cyr NM, Siddarth P, Baune BT, Lavretsky H. Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study. Int J Geriatr Psychiatry. 2016 May;31(5):510-7. doi: 10.1002/gps.4356. Epub 2015 Oct 15.

Reference Type: DERIVED

PMID: 26471432 (View on PubMed)

Other Identifiers

R01MH077650

Identifier Type: NIH

Identifier Source: secondary_id

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DATR A4-GPX

Identifier Type: -

Identifier Source: secondary_id

R01MH077650

Identifier Type: NIH

Identifier Source: org_study_id

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