CHICAGO — Methylphenidate appears to improve the symptoms of apathy in patients with early Alzheimer's, benefiting both patients and caregivers, according to the results of a small prospective trial.
After taking the drug for 12 weeks, patients in the study showed significantly reduced frequency and severity of apathy, while their caregivers reported significantly reduced distress, Dr. Prasad Padala said at the International Conference on Alzheimer's Disease.
“Apathy is the most common behavioral and psychiatric symptom of dementia, occurring in up to 90% of patients, and it's one of the earliest symptoms to appear,” said Dr. Padala of the University of Nebraska Medical Center, Omaha.
“Apathy also causes the caregivers a lot of stress, and it has a very high impact on functional status. Patients with apathy are three times more likely to be dependent on caregivers for their activities of daily living than are patients without apathy.”
It's thought that dysregulation of both the dopaminergic and noradrenergic systems contribute to apathy, Dr. Padala said. Because of this presumed etiology, he and his colleagues decided to investigate the use of methylphenidate in the disorder. The drug works on both of these systems.
The study enrolled 20 patients (mean age 70 years) at the Veterans Affairs Medical Center in Omaha. All had early Alzheimer's disease, with a mean Mini-Mental State Examination score of 23. Every patient had a score of greater than 30 on the Apathy Evaluation Scale; on this 72-point scale, anything above 30 is considered significant apathy.
At baseline, patients were assessed with the Neuropsychiatric Inventory's apathy subscale, which scores apathy on a 1- to 4-point scale for frequency and on a 1- to 3-point scale for severity. The score is a product of the ratings for frequency and severity. Caregivers rate their distress on a 1–5 scale, with 5 being the greatest.
Patients were started on 5 mg methylphenidate twice daily, and titrated up to 10 mg twice daily. Follow-up visits were conducted at 4, 8, and 12 weeks. After 12 weeks of treatment, patients significantly improved in their total item score from baseline (5 vs. 1.6), as well as their frequency/severity score (9 vs. 2). Caregiver distress also improved significantly, decreasing from 3.25 to 1. Other neuropsychiatric measures improved significantly as well, including the score on the Apathy Evaluation Scale, the Instrumental Activities of Daily Living Scale, and the Clinical Global Impressions-Severity subscale.
“Caregivers noted substantial improvements in the patients, such as increased energy, spontaneity, motivation, and ambition,” Dr. Padala said at the meeting sponsored by the Alzheimer's Association.
Two patients needed reductions in methylphenidate dosing: one because of loss of appetite and the other because of an increase in blood pressure. With this drug, as with many stimulants, an increase of 2–4 mm Hg in systolic blood pressure is not uncommon, Dr. Padala said. One patient developed a hacking cough that resolved spontaneously.
Dr. Padala is now conducting a 60-patient randomized, placebo-controlled trial.
He said he had no financial disclosures.