Aricept and PSP (2001 study)

A group member with progressive supranuclear palsy (PSP) asked me recently what I knew about two Alzheimer’s drugs — Aricept and Namenda — in treating PSP.

I’ve done a little bit of digging on the subject today and found a randomized, double-blind, placebo-controlled study funded by NIH done in 2001. The abstract follows.

Bottom line — these MDs do not recommend that those with PSP take Aricept (donepezil) because although the “Double Memory Test” scores will improve, status of activities of daily living (ADL) and mobility scores will worsen significantly.

I will search a bit on Namenda over the next few days. Since Namenda is NOT an acetylcholinesterase inhibit (Aricept is), this study will not apply.


Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy

I. Litvan, MD; M. Phipps, BA;, V. L. Pharr, MA; M. Hallett, MD; J. Grafman, PhD; and A. Salazar, MD

From the Cognitive Neuropharmacology Unit (Dr. Litvan, M. Phipps, and V.L. Pharr) and the Defense and Veteran Head Injury Program (Dr. Salazar), Henry M. Jackson Foundation; and the Medical Neurology Branch (Dr. Hallett) and the Cognitive Neuroscience Section (Dr. Grafman), National Institute of Neurological Disorders and Stroke, National Institutes of Health. (Robin’s note: Dr. I. Litvan is now at the University of Louisville in KY.)

Objective:­ There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age ± SD; 65.7 ± 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial.

Methods:­ Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status.

Results:­ Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened.

Conclusion:­ The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.