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

To investigate the efficacy of methylphenidate in depressed or apathetic geriatric patients.

Five "N of 1" trials (individual cross-over, double-blinded, randomized trials).

Department of Geriatrics, University Medical Center, Nijmegen, and two nursing homes in Nijmegen, the Netherlands.

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).

Methylphenidate (5 mg bid) and placebo (both for two subsequent days) in 5 weeks of randomized treatment blocks.

Montgomery Asberg Depression Rating Scale (MADRS), Apathy Evaluation Scale (AES)-clinician, the AES-informant, Barthel index and a semiquantitative checklist of adverse effects.

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 because AES could not be completed. None of the patients showed significant changes in the Barthel index. No side effects developed.

"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.