Toward individualized evidence-based medicine: Five "N of 1" trials of methylphenidate in geriatric patients

OBJECTIVES: To investigate the efficacy of methylphenidate in depressed or apathetic geriatric patients. DESIGN: Five "N of 1" trials (individual cross-over, double-blinded, randomized trials). SETTING: Department of Geriatrics, University Medical Center, Nijmegen, and two nursing homes in Nijmegen, the Netherlands. PARTICIPANTS: Patients suffered from depression due to a general medical condition (n = 2); depression resistant to antidepressive drugs (n = 1), chronic apathy due to mild and moderate severe dementia (n = 2). INTERVENTION: Methylphenidate (5 mg bid) and placebo (both for two subsequent days) in 5 weeks of randomized treatment blocks. MEASUREMENTS: Montgomery Asberg Depression Rating Scale (MADRS), Apathy Evaluation Scale (AES)-clinician, the AES-informant, Barthel index and a semiquantitative checklist of adverse effects. RESULTS: Among the three depressed patients, two showed significant improvement on the MADRS (P =.089 and P =.001; alpha = 0.10), one patient's apathy showed significant improvement on AES-clinician and -informant (P =.077 and P =.086). One apathetic patient's trial was stopped be cause AES could not be completed. None of the patients showed significant changes in the Barthel index. No side effects developed. CONCLUSION: "N of 1" trials are useful in evaluating efficacy of methylphenidate in depressed or apathetic geriatric patients. Single-patient trials can be a useful tool in pharmacotherapeutic decision-making in frail older subjects.