A Phase 3, randomized controlled clinical trial recently showed that methylphenidate, a drug often prescribed for patients with ADHD (commonly known as Ritalin), could relieve symptoms of apathy in Alzheimer’s.
Apathy is an extremely common symptom of Alzheimer’s. It impairs patients’ ability to socialize and maintain routines, activities that are central to preserving their wellbeing. So far, experts say no therapies have proven effective for treating apathy in Alzheimer’s, and over the years, scientists have looked for clues among existing drugs. One drug commonly prescribed for attention-deficit/hyperactivity disorder (ADHD), methylphenidate (mostly commonly marketed under the brand name Ritalin), can enhance the motivation of people with ADHD — and this has piqued researchers’ interest.
In Alzheimer’s, researchers believe the degeneration of the prefrontal cortex, a brain region that plays an intricate role in goal-oriented behaviors, could lead to symptoms of apathy. For ADHD patients, methylphenidate is thought to improve their symptoms by boosting the activity of chemical messengers known as norepinephrine and dopamine in the prefrontal cortex and other brain regions. Could it work for Alzheimer’s patients’ apathy too?
A Phase 3 clinical trial recently yielded encouraging results. Researchers tested methylphenidate in patients with Alzheimer’s and saw indications that it could provide some relief for their symptoms of apathy.
According to Dr. Carolyn Fredricks of the Department of Neurology at Yale University, apathy is a behavioral symptom that is often overlooked in Alzheimer’s, and it takes a major toll on both people living with Alzheimer’s and their caregivers. The search for effective treatments have fallen short in the past, but Fredricks said the recent study shows promising results.
“Despite its near-ubiquity, apathy is far from a benign neuropsychiatric symptom, and its impact on the clinical course of AD is devastating,” Fredricks, who was not involved in the study, wrote in an accompanying editorial. “Clinicians who have struggled to treat apathy in their patients with AD should take heart at this evidence that methylphenidate may be a safe and efficacious option.”
For the trial, published in JAMA Neurology, researchers enrolled 200 Alzheimer’s patients with frequent and/or severe apathy. Among other criteria, those with significant agitation, aggression, delusions, hallucinations or a major depressive episode were excluded from the study. The team then randomized the participants, who had a median age of 76, into one group that received methylphenidate and a placebo group.
After six months, the scientists observed a larger decrease in the treatment group’s assessment scores of apathy, compared to the placebo group. The greatest decrease in apathy scores occurred during the first two months of treatment, an effect that lasted until the end of the study period. Meanwhile, the researchers found no differences in measures of cognitive functions, caregiver burden and quality of life between the two groups.
“Methylphenidate offers a treatment approach providing a modest but potentially clinically significant benefit for patients and caregivers,” the clinical trial’s investigators wrote. “The efficacy has a relatively early onset and its effect is sustainable for at least six months.”
These results follow preliminary evidence from two smaller clinical trials of the safety and efficacy in treating the apathy of Alzheimer’s patients with methylphenidate.
Research into therapies for the behavioral symptoms of Alzheimer’s like apathy is critical, Fredricks explained. Apathy, often misdiagnosed as depression, is closely linked with patients’ ability to carry out daily activities, quality of life and even risk of mortality. For some caregivers, the increased demands of care can be too much to handle, and patients may thereby be admitted to long-term care earlier than expected.
According to Fredricks, past studies examining the effects of various treatments, including antidepressants, antipsychotics and cholinesterase inhibitors, “have been inconclusive at best” for treating Alzheimer’s patients’ apathy. But, she said the recent study is the “first phase 3 randomized clinical trial showing efficacy of any treatment for apathy in Alzheimer’s disease.”
She added, “As evidence builds for the far-reaching negative effects of apathy and other neuropsychiatric symptoms in patients with AD and while we await definitive disease-modifying therapies, identifying effective treatments for the neuropsychiatric symptoms of AD is of the utmost importance.”