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Zonisamide with Levodopa May Reduce Risk of Dementia, Other Parkinson’s-related Symptoms, Japanese Study Suggests

Zonisamide, Parkinson's

Japanese researchers have reported that zonisamide — an antiparkinsonian medicine approved in Japan as a combination therapy with levodopa — may be associated with a lower risk of dementia, insomnia, and gastric ulcers in Parkinson’s disease, compared with other non-levodopa medicines.

Their research was published in the study “Comparison of zonisamide with non-levodopa, anti-Parkinson’s disease drugs in the incidence of Parkinson’s disease-relevant symptoms,” in the Journal of the Neurological Sciences.

Marketed under the name Zonegran in the U.S. for adjunctive therapy in the treatment of partial seizures in adults with epilepsy since 2000, zonisamide has been approved in Japan (where it’s called Trerief) as an antiparkinsonian agent to be used in combination with levodopa therapy.

Parkinson’s patients have low levels of the chemical messenger dopamine in their brains due to disease-specific death of dopaminergic (meaning “dopamine-producing”) neurons. Among other brain functions, sleep, memory, and movement are all affected by the lack of dopamine and, as such, patients often develop insomnia and dementia, along with the hallmark motor symptoms of Parkinson’s disease.

Levodopa (L-DOPA) is the first choice when it comes to effective Parkinson’s motor symptom control, and as the disease progresses, patients typically need to gradually increase their treatment dose for maximum benefit. After that, they might sometimes experience reappearance or worsening of symptoms due to diminishing effects of dopaminergic therapy. Because of this, most patients will require combination therapy at some point.

Although zonisamide’s mechanism of action is not yet fully understood, studies indicate the compound acts by preventing the breakdown of dopamine, increasing its levels in the brain, and relieving Parkinson’s symptoms. Evidence also suggests that the medicine may have neuroprotective effects.

Clinical trials have shown zonisamide significantly alleviates Parkinson’s motor and non-motor symptoms. “However, partly because zonisamide is off-label for PD [Parkinson’s disease] except for in Japan, situations in which it is more suitable than other drugs have not been sufficiently elucidated,” the researchers noted.

For the study, investigators from Ehime University Graduate School of Medicine in Japan sought to evaluate if zonisamide use in Parkinson’s patients, 40 years or older, was associated with the time of onset of Parkinson’s disease-relevant symptoms, mainly mental, autonomic nervous system, movement, and gastric symptoms.

The results were compared to seven other non-levodopa drug classes that are often used when primary therapy is not fully effective (also referred to as second-line therapy).

For this analysis, levodopa was not considered as a comparison drug to zonisamide, as the majority of study participants were taking levodopa together with zonisamide or another second-line medicine.

Patients had to be on levodopa or other antiparkinsonian medicine without having switched to or recently combined use with other drug classes.

Using a set of statistical approaches, the researchers investigated the time it took for a given symptom of interest to occur while participants were on zonisamide, compared with other non-levodopa medications indicated for Parkinson’s disease.

Of the 9,157 studied subjects, those who were on COMT inhibitors, anticholinergics, or amantadine were two to nearly five times more likely to develop dementia. In addition, zonisamide use was found to be associated with a lower risk of developing insomnia and gastric ulcers, compared with three other non-levodopa medicines.

An increased prevalence of gastric ulcers has long been associated with Parkinson’s disease, and they are generally accepted as a symptom experienced by patients.

“Zonisamide also showed significant lower risk in the incidence of orthostatic hypotension, constipation, and limb fracture,” the researchers wrote, adding that the treatment was, however, also associated with a higher risk “in the incidence of depression and aspiration pneumonia than at least one of the other drug classes.”

Compared with three other classes of medications, zonisamide appears to be associated with a lower risk of developing dementia, insomnia, and gastric ulcers in Parkinson’s disease. However, it was not always the same three-treatment set that was found to be somehow associated with the lowest risk for a given symptom.

Nonetheless, “[t]here may be a potential clinical impact of zonisamide on some of the [Parkinson’s disease]-relevant symptoms,” the authors concluded.

The post Zonisamide with Levodopa May Reduce Risk of Dementia, Other Parkinson’s-related Symptoms, Japanese Study Suggests appeared first on Parkinson’s News Today.

The Dilemmas of Having Parkinson’s Disease: It Could Happen to You

going to the bathroom

Sherri Journeying Through

Warning: The names of those involved have been excluded to protect the embarrassed.

The air could sure use some cleaning out. I try to eat more fiber, but when I eat more fiber, my husband finds the air needs a good cleaning. So, I asked my doctor what I should do. He said I should be thankful I have Parkinson’s and am unable to smell the odors I make, and also that I should be grateful I can go to the bathroom. Having PD exacerbates the constipation problem.

I’m thankful I can go to the bathroom.

Isn’t everybody? I just wish it didn’t take so awfully long. I tried hissing one time while I was on the toilet, as someone in my support group suggested. They said it would relax my muscles. But it just distracted me, and I concentrated too much on whether anyone could hear me hissing and I forgot to relax. Or, I guess I did relax but not in the way I wanted, and I forgot what I was trying to do.

So, after that, I tackled putting the new satin sheets on my bed, determined that tonight would be the night I would get a good night’s sleep — for the first time in six years. Due to past experience, I didn’t have my heart set on that good night’s sleep. I’m not that foolish. But I was hopeful. At least I might be able to move easily while in bed for a change. 

I even bought satin pajamas to add to the ease of movement.

Bad idea. When my bottom side made contact with the side of the bed, try as I might to hold onto the nightstand for support, my body slid down to the floor with a thud. After struggling to get back up, I tried it again with the same result. 

With the next attempt, I had put my grandson’s side rails — which he uses when he spends the night — on my bed and crawled onto the bed in my regular fashion, like a dog trying to settle into his bed for the night. Around I circled on top of the bed, trying to find that comfy, sweet spot. Upon finally finding it, I gently laid down, pulled up the covers and laid very still — until I convinced myself, just short of a panic attack, that I had to pee one more time. 

I knew I wasn’t going to make it.

I slid to the end of the bed and landed with a thud onto the floor once again. By the time I stood up, I knew I wasn’t going to make it to the bathroom in time and wet my pants. 

After showering again for the night, I put on my flannel PJs, grabbed my favorite quilt and the pillow with the satin pillowcase, and went to the couch. After my pillow won the war of sliding out from under my head, I finally took off the pillowcase and went to sleep.

For sale: One set of satin sheets. Cheap.

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Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

The post The Dilemmas of Having Parkinson’s Disease: It Could Happen to You appeared first on Parkinson’s News Today.