Zonisamide for Epilepsy May Ease Parkinson’s Motor Symptoms: Study
Approved anti-seizure medication also linked to reduced 'off' time
Zonisamide, an epilepsy medication approved in the U.S. for some seizure-causing disorders, may reduce the motor symptoms of Parkinson’s disease, according to a review study of clinical trial data.
The findings also suggest the therapy is associated with improvements in daily life activities for Parkinson’s patients, and with reductions in “off” time — the period between medication doses when symptoms are not being fully controlled.
“Our results showed that the improvement in motor function with zonisamide was significant,” the researchers wrote.
Still, the scientists said larger studies are needed to confirm the therapeutic benefits of zonisamide in this patient population.
The review study, “Zonisamide’s Efficacy and Safety on Parkinson’s Disease and Dementia with Lewy Bodies: A Meta-Analysis and Systematic Review,” was published in BioMed Research International.
Zonisamide, discovered in Japan in the 1970s, is approved in the U.S. and elsewhere to treat some forms of epilepsy. It is marketed as Zonegran, with generics available. The therapy’s biological effects appear numerous and complex, affecting a number of neurological signaling pathways.
Effects on Parkinson’s motor symptoms
Some studies have suggested that zonisamide may help ease some motor symptoms of Parkinson’s disease. The therapy was approved in Japan in 2018, under the brand name Trerief, for Parkinson’s patients who saw insufficient results with standard treatment.
Now, a team led by scientists at Shandong University of Chinese Medicine, in China, conducted a review of published data, up to April 18, 2022, using the Pubmed, Cochrane Library, Web of Science, and Embase databases.
Their goal was to assess zonisamide’s effects in people with Parkinson’s disease or the related condition dementia with Lewy bodies (DLB).
The meta-analysis included results from seven appropriately-controlled clinical trials that compared zonisamide against a placebo. Four of the studies were conducted in Parkinson’s patients, and the other three in those with DLB.
All of the trials were conducted in Japan between 2007 and 2021. Collectively, they included 916 people with Parkinson’s and 833 with DLB. The first study tested three doses of zonisamide (25, 50, and 100 mg/day), after which the remaining six trials only included the two lower doses.
The studies ranged in length from 3.5 months to about a year, and in all of them, participants could continue their standard approved Parkinson’s treatments.
Pooled data on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, which assesses the severity of motor symptoms, showed that zonisamide treatment significantly reduced (eased) scores by an average of 2.27 points relative to a placebo.
Subgroup analyses showed a significant effect in both patient groups, but it appeared to be “more pronounced for DLB patients,” the researchers wrote.
“These motor changes measured by the UPDRS Part III also confirm the significant improvement in motor function of zonisamide in [Parkinson’s] and DLB patients,” the team added.
Scores of UPDRS Part II assessing “off” times — a measure of how often motor symptoms affecting daily activities are not being adequately controlled with standard therapy — were only available for three of the four Parkinson’s trials.
Data showed that these scores also were significantly reduced with zonisamide, by an average of 0.81 points, versus a placebo. A significant drop, by 0.67 points on average, also was observed in daily “off” time.
The duration of dyskinesia — uncontrolled, involuntary movements common in Parkinson’s — and its associated disability and pain, were assessed with the UPDRS Part IV. Results showed that dyskinesia duration was significantly less likely to get worse for patients on zonisamide.
However, zonisamide was not associated with a consistent statistical effect for reducing dyskinesia duration, or dyskinesia-associated disability and pain.
More research needed on dyskinesia effects
While the therapy “appears to [reduce] the duration of dyskinesia … its effect on pain and disability caused by dyskinesia needs to be supported by further research data and results,” the researchers wrote.
Analyses of safety-related outcomes with the 25 mg and 50 mg doses showed that rates of drowsiness were significantly higher for Parkinson’s patients on zonisamide than on a placebo. Among DLB patients, reduced appetite and bruising were significantly more common in the zonisamide group than in the placebo group.
Other safety-related outcomes did not show statistically significant differences between the zonisamide and placebo groups.
These findings highlight the significant benefits in motor function found with zonisamide in Parkinson’s patients. Moreover, the review shows the therapy “has a significant positive impact on the improvement of activities of daily life, wearing off, and duration of dyskinesia,” the researchers wrote.
“We concluded that 25 mg and 50 mg doses of zonisamide are relatively safe and provide good improvement in the treatment of both [Parkinson’s disease] and DLB, but perhaps more dose options should also be tried in future trials to explore for the highest patient benefit,” they added.
The team noted that these analyses were limited by the relatively short duration and small size of the trials, as well as the fact that all of the studies were conducted in Japan.
Future studies should be larger in scope, longer, and also focus on the underlying mechanisms of zonisamide’s positive effects in Parkinson’s and DLB, they said.
Trerief is marketed in Japan by Sumitomo Dainippon Pharma, which was not involved in this study.