Motor symptoms improved with add-on therapy of seizure medication.
Researchers in Japan published promising data on a Phase II clinical trial on an existing medication (for seizures) in people with dementia with Lewy bodies. When used in addition to steady treatment with levodopa (i.e. “add-on” treatment to standard care), zonisamide appeared to improve motor symptoms in DLB without worsening psychiatric symptoms, a common side-effect in DLB.
This study, led by Miho Murata, MD, PhD, was a Phase II, placebo-controlled, randomized, double-blind study. This means the study was a pilot study designed to measure the drug’s effectiveness in treating certain LBD symptoms, and neither the researcher or study participants knew who was getting the active medication.
Zonisamide was already approved in Japan in 2009 as an add-on treatment for motor symptoms in Parkinson’s disease (PD). The DLB study involved 158 participants from over 60 medical institutions and ran from March 2013 to April 2014.
Study subjects were already on a stable course of levodopa and 75% were also taking anti-dementia medications. The study began with a run-in period in which everyone received a placebo for 4 weeks. Then participants were randomized to continue with a placebo, a 25 mg or a 50 mg dose of zonisamide once daily for 12 weeks. 137 participants completed the study.
Meeting its primary endpoints, improvements in motor symptoms were greater in those taking zonisamide over placebo, with the 50 mg dosage resulting in the largest improvement. There were no significant changes in the study’s secondary endpoints of cognitive function, psychiatric symptoms or caregiver burden. The most common side effects, also seen in the PD clinical trials, were weight loss, decreased appetite and rash.
While further study is needed in a larger clinical trial, this Phase II trial suggests zonisamide may be a useful add-on treatment to levodopa in those with DLB who do not tolerate higher doses of levodopa. This study is also considered a major accomplishment for adding proof that successful clinical trials are feasible in DLB, a disorder that still has no FDA-approved treatments available.
The study first appeared online in Neurology in January, 2018 and was funded by Sumitomo Dainippon Pharma Co., Ltd.