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

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.