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

Condition(s) targeted: Depression

Intervention: Citalopram (Drug); Methylphenidate (MPH) (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Helen Lavretsky, MD, Principal Investigator, Affiliation: University of California, Los Angeles

Overall contact:
Helen Lavretsky, MD, Phone: 310-794-4619, Email: hlavrets@ucla.edu

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

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Hamilton Depression Rating Scale (HDRS) scores

Secondary outcome: Cognitive tests; quality of life, disability, and safety assessments; candidate genes; and drug levels

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.

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

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

Helen Lavretsky, MD, Phone: 310-794-4619, Email: hlavrets@ucla.edu

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

Starting date: February 2008
Ending date: February 2013
Last updated: August 18, 2008