Tuesday, September 28, 2021

Methylphenidate May Reduce Symptoms of Apathy in Patients With Alzheimer’s Disease

Methylphenidate may be able to help reduce symptoms of apathy in people with Alzheimer’s disease, according to a report published Monday in JAMA Neurology.

“Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality,” wrote Jacobo Mintzer, M.D., M.B.A., of the Medical University of South Carolina and colleagues. “Methylphenidate offers a treatment approach providing a modest but potentially clinically significant benefit for patients and caregivers.”

For the study, the researchers recruited individuals with possible or probable Alzheimer’s disease (AD), mild to moderate cognitive impairment, and frequent and/or severe apathy from clinical centers specializing in dementia care. Two hundred participants (aged 71 to 81 years) were randomly divided into either the methylphenidate or placebo group. The participants took identical-appearing capsules (capsules contained either 5 mg of generic methylphenidate or placebo), starting with one capsule two times a day, then two capsules twice daily for six months. The researchers followed up with the participants by telephone at days 15, 45, and 75 after the start of the study and in person monthly for six months. Participants and their caregivers received a standardized psychosocial intervention, including a 20- to 30-minute counseling session at each visit, educational materials, and 24-hour availability of study staff for crisis management, Mintzer and colleagues noted.

The researchers conducted monthly structured interviews with the participants’ caregivers, using the Neuropsychiatric Inventory (NPI) to assess the presence and severity of 12 neuropsychiatric symptoms, including apathy. The Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) scale, administered by an independent clinician, was also used to assess clinically meaningful change in the participants’ apathy at six months.

Mintzer and colleagues noted that a larger decrease was found from baseline to six months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean between-group difference, −1.25), with the largest decrease in the NPI apathy score observed in the first 100 days. At six months, the odds ratio of having an improved rating on the ADCS-CGIC for methylphenidate compared with placebo was 1.90. “[I]t is important to note that there were no group differences in any of the cognitive measures, suggesting that the effect of the treatment is specific to the treatment of apathy and not a secondary effect of improvement in cognition,” the researchers added.

“While methylphenidate will not be an option for those individuals with medical or psychiatric contraindications to stimulants, the present study demonstrates that it is generally safe and well tolerated for the target population,” wrote Carolyn Fredericks, M.D., of Yale University in an accompanying editorial. “Despite its near ubiquity, apathy is far from a benign neuropsychiatric symptom, and its impact on the clinical course of AD is devastating. 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 related information, see the American Journal of Psychiatry article “Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer’s Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.”

(Image: iStock/katleho Seisa)

Learn About Changes to Clozapine REMS Requirements

The FDA recently approved modifications to the Clozapine Risk Evaluation and Mitigation Strategy (REMS). All prescribers and pharmacies must be re-certified by Monday, November 15, to be able continue prescribing/dispensing clozapine. SMI Adviser will host a webinar on how to navigate this process on Wednesday, September 29, at 3 p.m. ET.


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