Zonisamide Add-on Fails to Ease Tremor-dominant Parkinson’s

Anti-seizure medication tested in pilot study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Illustration shows several hands holding medications.

Add-on treatment with a low dose of zonisamide, an anti-seizure medication, failed to significantly ease tremor in a pilot study of people with a tremor-dominant form of Parkinson’s disease.

However, when researchers preformed their analysis and included all people —  even those who dropped out of the study — to understand what could happen in a best-case scenario, they found that tremor may be significantly less severe in zonisamide-treated patients versus those treated with placebo.

This means there is a possibility that zonisamide may have an effect on tremor, the researchers noted, writing that “it is imperative to conduct larger studies with a robust follow-up to test this finding.”

The study, “Zonisamide add-on in tremor-dominant Parkinson’s disease – A randomized controlled clinical trial,” was published in the journal Parkinsonism & Related Disorders.

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Parkinson’s occurs due to the damage and loss of certain nerve cells in the brain, causing motor symptoms that usually begin as tremor, slowness of movement (bradykinesia), and difficulty walking and balancing.

While there are some medications available today that may ease at least some of these symptoms, it can be difficult to find one that works well enough for all people who experience tremor.

Zonisamide, sold as Zonegran with generics available, is approved in the U.S. and elsewhere to treat some forms of epilepsy. It also is approved as an add-on treatment in Japan to treat Parkinson’s.

A number of trials in people with Parkinson’s have shown that treatment with zonisamide may reduce motor symptoms and “off” time, which occurs when the effects of levodopa wear off and symptoms return before another dose of levodopa can be taken.

Now, a team of researchers in India conducted another trial to test how well zonisamide may work for people with tremor-dominant Parkinson’s.

Study design

The study included 52 adults (46 men and six women) who had a diagnosis of Parkinson’s and experienced tremor as their main disease manifestation over other motor symptoms despite being on dopamine replacement treatment.

They were assigned randomly to receive either a dose of 25 mg of zonisamide daily for 12 weeks (about three months), or a placebo, in addition to their standard dopamine replacement treatment schedule.

There were 26 patients in each group, with the mean age (60.5 vs. 60.3 years) and median disease duration (5 vs. 4.8 years) similar between the two groups.

Unified Parkinson’s Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores were assessed and recorded at the beginning of the study (baseline), as well as at the end of the treatment period.

Some of the patients dropped out of the study or were lost to follow-up, so only data from 19 patients in the zonisamide group and 18 patients in the placebo group were used for this analysis.

At the beginning of the study, the mean UPDRS score on the item that assesses tremor was similar in the two groups. After treatment, the score dropped by a median 26.14 points in the zonisamide group and by 8.33 points in the placebo group. Although the change from baseline was not significantly different between the two groups, there was a trend toward a greater improvement in the UPDRS tremor score in the zonisamide group.

‘Best-case scenario’ analysis

Because the number of patients with data available was relatively small, the researchers performed a type of analysis that mimics a “best-case scenario,” which included all the randomized patients (26 in each of the groups).

In this scenario, all patients with missing data in the zonisamide group are assumed to have good outcomes, and all those with missing data in the placebo group are assumed to have poor outcomes.

When this new analysis was run, it was found that tremor would be significantly less severe in the zonisamide group than in the placebo group. However, “larger studies are required to confirm this finding,” the researchers wrote.

Contrary to previous trials, there were no significant differences in UPDRS scores (non-motor and motor aspects of experiences of daily living, motor symptoms), bradykinesia, movement rigidity, and total TETRAS scores, between the treatment group and placebo.

Low-dose zonisamide was found to be relatively safe. Two patients in the zonisamide group experienced drowsiness as a side effect, which led to treatment discontinuation in one of them. One other patient in the zonisamide group experienced dizziness. There also were two patients in the placebo group who experienced drowsiness or excessive fatigue.