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Topiramate as an Adjunct to Amantadine in the Treatment of Dyskinesia in Parkinson's Disease

Dyskinesia is a term used to describe involuntary movements that develop as side effects of dopamine drugs used to treat Parkinson's disease. Dyskinesias are frequent and disabling to many patients. They can interrupt smooth coordinated movements, affect communication and disrupt activities of daily living. Currently, among medications to treat dyskinesia, only amantadine is effective and readily available. A recent laboratory study documented that a readily available drug, topiramate, provided additional improvement with amantadine in parkinsonian pre-clinical models with dyskinesia. In fact, the benefit of the combination of topiramate and amantadine proved to be better than the benefits from either one alone even if the individual effects were added. This study will build on the laboratory information to test topiramate in Parkinson’s disease (PD) patients with dyskinesia who are already taking daily amantadine.

Project Description:
This study will enroll PD patients who have dyskinesia and who are already receiving amantadine. Subjects will be assigned either placebo or topiramate, which will be gradually increased to a best dose that balances improvement and any potential side effects. Participants will be monitored to see if the study drug has positive effects on dyskinesia and if they can safely and comfortably tolerate the two drugs in combination. The study will last 18 weeks and is double-blind, meaning neither patient nor researcher will know if each patient has received the placebo or the drug. Over six weeks researchers will increase the drug dose up to 150mg per day. Patients will continue taking the medication or placebo for four weeks at the best tolerated dose. Five sites are conducting the study and recruiting subjects with dyskinesia, ranging from mild to severe, who have been on stable doses of amantadine for at least four weeks prior to study entry.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The purpose of this research study is to see how taking the study drug (topiramate or placebo), along with stable doses of amantadine, will affect dyskinesias in subjects with PD. Topiramate is approved by the U.S. Food and Drug Administration (FDA) for the treatment of epilepsy and prevention of migraine headaches but not for use in PD. Prior studies have established that both placebo treatment and topiramate treatment may improve dyskinesias in PDpatients. Therefore it is possible that subjects may experience a lessening of the severity of their involuntary movements.

Anticipated Outcome:
The anticipated outcomes are that i) topiramate treatment will be safe and well-tolerated in patients and ii) those patients receiving both topiramate and amantadine will have reduced dyskinesia in comparison to those patients receiving only amantadine and placebo tablets.


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Final Outcome

The aim of this study was to see if the medication topiramate would decrease dyskinesia in patients with Parkinson's disease (PD) already on amantadine.  We tested this idea in a double-blind, placebo-controlled study enrolling 42 patients with PD.  Although the improvement was greater in the topiramate group than placebo, the outcome of the study as well as the conditional power estimates fail to support a role of topiramate at the doses studied in treating dyskinesia in PD.


  • Glenn T. Stebbins, PhD

    Chicago, IL United States

  • Christopher G. Goetz, MD

    Chicago, IL United States

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