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Stimulant Drug May Reduce Apathy in People With Alzheimer’s Disease

October 18, 2021

The drug methylphenidate, a stimulant also known as Ritalin, may reduce apathy in people with Alzheimer’s disease. The benefits were modest but the findings are important, because apathy is a very common problem in people with Alzheimer’s disease, and little is known about how to treat it.

Apathy, which is marked by a lack of interest and enthusiasm, typically appears early in the course of Alzheimer’s and can worsen as the disease progresses. Other behavioral problems of Alzheimer’s like aggression and agitation get more attention, but apathy is also a common source of distress for family members caring for a loved one with the disease. A person with Alzheimer’s who has apathy shows little initiative, which can increase the risk that they don’t take care of themselves, raising the risk of other medical problems and increasing demands on caregivers. Apathy also means they don’t engage enough in social and stimulating activities, potentially increasing the disease progression.

For the study, a late-stage trial, researchers looked at 200 men and women with early to moderate Alzheimer’s disease. Half were given methylphenidate in a dosage of 10 milligrams twice a day. The others got a placebo drug.

After six months, those taking methylphenidate show improvements in behavioral tests that monitor apathy. The benefits were modest, appearing two months into the treatment and continuing through the study period. The drug also appeared to be generally safe and well tolerated, with only minor side effects.

“Methylphenidate offers a treatment approach providing a modest but potentially clinically significant benefit for patients and caregivers,” wrote the study’s lead author, Dr. Jacobo Mintzer, of the Ralph H. Johnson VA Medical Center in Charleston, South Carolina, and colleagues. “Methylphenidate may be useful for the treatment of apathy in individuals with Alzheimer disease, which can reduce symptoms and caregiver burden.”

Although patients showed improvements in apathy scores, the authors cautioned that benefits were modest (that could be due to the modest study size). In addition, patients did not show improvements in tests that measure how successfully they complete activities of daily living, like getting dressed and preparing meals. Nor did the drug lead to improvements in tests of memory and thinking skills. It might take longer than six months to observe significant differences on those parameters, or it might also be function of the age of the patients.

Apathy affects up to 90 percent of people with Alzheimer’s disease, wrote Dr. Carolyn Fredericks of Yale University in an accompanying editorial. “Despite the severity of apathy’s impact on patients with dementia and their caregivers, it is notoriously difficult to treat, and no therapies to date have proven to be effective,” she said.

The study was a phase 3 trial, and the drug has not yet been approved specifically to treat the apathy of Alzheimer’s disease. Methylphenidate is currently approved to treat attention-deficit hyperactivity disorder and narcolepsy, a neurologic disorder which causes people to suddenly fall asleep; for those indications in adults, the drug is given in a dose of 20 to 30 mg per day, or up to 60 mg a day.

The drug would also not be appropriate for people who cannot tolerate stimulant medications. In the current trial, people with Alzheimer’s who had major depression or significant agitation, aggression, delusions or hallucinations were excluded from the study. It is likely that the stimulating nature of methylphenidate could make these conditions worse.

Still, as Dr. Fredericks noted, “Symptoms such as agitation and aggression attract more attention and more therapeutic intervention as potential threats to patient and caregiver safety. But quieter symptoms, such as apathy, are far more common, particularly in the earlier stages of illness, and have an insidious and highly negative impact on clinical course.” Anything that can help to ease apathy could have significant benefits on the course of the disease.

“As evidence builds for the far-reaching negative effects of apathy and other neuropsychiatric symptoms in patients with Alzheimer’s disease, and while we await definitive disease-modifying therapies, identifying effective treatments for the neuropsychiatric symptoms of Alzheimer’s is of the utmost importance,” she wrote. 

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University. 

Source: Jacobo Mintzer, MD, MBA; Krista L. Lanctot, PhD; Roberta W. Scherer, PhD; et al: “Effect of Methylphenidate on Apathy in Patients With Alzheimer’s Disease.” JAMA Neurology, Sept. 27, 2021

Carolyn Fredericks, MD: “Methylphenidate for Apathy in Alzheimer Disease—Why Should We Care?” (editorial). JAMA Neurology, September 27, 2021

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