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Adjunctive Zonisamide May Improve Motor Function in Dementia With Lewy Bodies

January 30, 2018

By Will Boggs MD

NEW YORK (Reuters Health) - Zonisamide improves parkinsonism symptoms accompanying dementia with Lewy bodies (DLB), researchers from Japan report.

The parkinsonism symptoms frequently reported by patients with DLB often respond to treatment with levodopa. Levodopa must be used with caution in these patients, however, because it can induce psychiatric symptoms such as hallucinations and delusions.

Dr. Miho Murata from National Center of Neurology and Psychiatry, Tokyo, Japan, and colleagues investigated the efficacy and safety of two different doses of zonisamide as an adjunct to levodopa in a randomized, placebo-controlled trial of 158 patients with DLB. The findings were reported online January 24 in Neurology.

All three groups experienced improvements in Unified Parkinson's Disease Rating Scale (UPDRS) part 3 (motor examination) total score at week 12, compared with baseline. However, improvements were significantly greater in the zonisamide 50-mg group and in the zonisamide 25-mg group than in the placebo group.

In contrast, the changes from baseline to week 12 for each total score in UPDRS part 1 (nonmotor experiences of daily living), 2 (motor experiences of daily living), 4 (motor complications), and 1-4 were similar between the zonisamide groups and the placebo group.

Total scores for the Mini-Mental State Examination, Neuropsychiatric Inventory, and Zarit Burden Inventory did not change significantly from baseline in any group, suggesting to the researchers that "administration of zonisamide did not worsen cognitive function, behavioral and psychological symptoms of dementia, or caregiver burden.”

The overall incidence of adverse events was comparable between 25-mg zonisamide (50.0%) and placebo (43.1%) but was higher for 50-mg zonisamide (65.3%).

“Although these findings suggest zonisamide is clinically safe and useful for the treatment of parkinsonism in patients with DLB, it should be noted that this study was performed with a relatively small number of patients,” the researchers caution. “Further studies are needed to investigate the efficacy of zonisamide in a large number of participants.”

Dr. Linda A. Hershey from University of Oklahoma Health Sciences Center, Oklahoma City, who coauthored an accompanying editorial, told Reuters Health by email, "I think the most interesting result from this study was the fact that zonisamide 50mg/day was able to improve motor function in DLB parkinsonism patients without worsening their visual hallucinations or other behavioral symptoms. The drugs we currently use to improve motor function in DLB often worsen the hallucinations.”

“Right now, we can be guided by this study to use zonisamide as an adjunct to levodopa in treating DLB parkinsonism,” she said. “New trials will be needed to learn whether it is effective for DLB parkinsonism patients who are not taking levodopa.”

Dr. Hershey added, “DLB is the second most common neurodegenerative cause of dementia (second to Alzheimer's disease). It is often confused with other diseases, such as Alzheimer's disease or Parkinson's disease. Since the symptoms of DLB can be managed in the early stages, it is important that every new DLB patient be evaluated by a neurologist as soon as the disease is suspected (tremors, slowness, sleep disorder, hallucinations, daytime sleepiness, etc.).”

Dr. Murata did not respond to a request for comment.

Sumitomo Dainippon Pharma Co., maker of Zonegran (zonisamide), supported the study; employed three of the seven authors; and had various relationships with the other four.


Neurology 2018.

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