Tapping an old drug for a new indication: Zonisamide effective for dementia with Lewy bodies

For patients with dementia with Lewy bodies, adding zonisamide to levodopa may improve movement symptoms without causing added psychiatric symptoms, according to a recent study published in Neurology.

Zonisamide, a sulfonamide anticonvulsant and a carbonic anhydrase inhibitor, is currently approved for the treatment of seizures, but how it controls seizures is unknown. Levodopa is an antiparkinsonian dopamine precursor that is approved for the treatment of Parkinson’s disease.

“We found that adding zonisamide to the current dose of levodopa was safe and improved movement symptoms in those with dementia with Lewy bodies without magnifying hallucinations, delusions, or agitation,” said study author Miho Murata, MD, PhD, National Center of Neurology and Psychiatry in Tokyo, Japan.

For their randomized, double-blind, phase 2 study, Dr. Murata and colleagues included 158 subjects diagnosed with early dementia (average disease duration of 1.5 years) with Lewy bodies. Subjects were randomized to either zonisamide at 25 or 50 mg/d or placebo, added to whatever medications they were already taking.

Researchers quantified patients’ movement symptoms, cognitive function, behavior, and psychological symptoms. The primary endpoint was change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 total score by week 12.

In all, 21 patients discontinued treatment, and 137 completed the study. At baseline, the average movement test score among these patients was 32 (scale: 0-108).

At week 12, Dr. Murata and colleagues found significant improvements in UPDRS part 3 total scores in patients treated with the 50-mg dose of zonisamide compared with placebo (difference: -4.1; 95% CI: -6.8, -1.4; P=0.003). Cognitive function, behavioral and psychological symptoms of dementia, and caregiver burden did not worsen with zonisamide treatment.

The overall incidence of adverse events was higher in patients treated with the 50-mg dose of zonisamide than with the 25-mg dose or placebo (65.3%, 43.1%, and 50.0%, respectively). The incidence of serious adverse events was similar among all three groups.

“There is an urgent need for new treatments for dementia with Lewy bodies,” said Linda A. Hershey, MD, PhD, University of Oklahoma Health Sciences Center in Oklahoma City, OK, and Fellow of the American Academy of Neurology, who wrote an accompanying editorial to this study. “The successful execution of this trial is a major accomplishment, which provides evidence that future trials are warranted.”

The study was supported by Sumitomo Dainippon Pharma Co., Ltd, the maker of zonisamide.