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Adjunct zonisamide improves parkinsonism in dementia with Lewy bodies

Patients with dementia with Lewy bodies who took zonisamide as an adjunct to levodopa experienced improvements in parkinsonism without worsening cognitive function or psychiatric symptoms, according to study findings.

“The mechanism of action of zonisamide on [Parkinson’s disease] has not been fully elucidated,” Miho Murata, MD, PhD, from the department of neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, and colleagues wrote in Neurology. “A previous study of three patients with [dementia with Lewy bodies] reported that zonisamide improved parkinsonism and reduced caregiver burden without deteriorating cognitive function or behavioral or psychological symptoms.”

In a phase 2, placebo-controlled, randomized, double-blind study, researchers studied whether zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with dementia with Lewy bodies would be effective and safe. The study consisted of a 4-week run-in period and a 12-week treatment period where the investigators compared the efficacy of once-daily zonisamide (25 mg or 50 mg) vs. once daily placebo tablets in outpatients diagnosed with probable dementia with Lewy bodies. They evaluated participants’ Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 total scores every 4 weeks until 12 weeks to determine change from baseline. They also assessed cognitive function, behavioral and psychological symptoms of dementia, caregiver burden and safety.

Of 137 participants who completed treatment, Murata and colleagues observed significantly greater improvement in UPDRS part 3 total score at week 12 in the zonisamide 50-mg group compared with placebo (between-group difference –4.1; 95% CI –6.8 to –1.4; P = .003). Although analysis showed a reduction in UPDRS score from baseline at week 4 in all groups, the score remained constant up to week 12 for placebo but continued to decrease in the zonisamide groups. Participants receiving 50 mg of zonisamide also had significantly lower scores at week 8 (–2.8; 95% CI –5.3 to –0.4; P = .022) and week 12 (–5.1; 95% CI –8 to –2.2; P < .001) compared with placebo. Furthermore, zonisamide did not worsen cognitive function, behavioral and psychological symptoms of dementia or caregiver burden. Overall incidence of adverse events was higher in the zonisamide 50 mg than the 25 mg and placebo groups.

“Zonisamide is effective for the treatment of motor symptoms and wearing-off related to [Parkinson’s disease],” Murata and colleagues wrote. “Although these findings suggest zonisamide is clinically safe and useful for the treatment of parkinsonism in patients with [dementia with Lewy bodies], it should be noted that this study was performed with a relatively small number of patients. Further studies are needed to investigate the efficacy of zonisamide in a large number of participants.”

Disclosures: Murata reports receiving honoraria for consulting and/or lecturing from Sumitomo Dainippon Pharma Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Nihon Medi-Physics Co. Ltd., FUJIFILM Pharma Co. Ltd., Hisamitsu Pharmaceutical Co., Inc. and AbbVie GK. He also reports grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Agency for Medical Research and Development, and the Ministry of Health, Labor and Welfare of Japan. Please see the study for all other authors’ relevant financial disclosures.