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Topiramate Effective in Treating Essential Tremor: Presented at MDS

By Paula Moyer

ROME, ITALY -- June 18, 2004 -- The anticonvulsant agent topiramate (Topamax) is effective at addressing several symptoms of essential tremor, according to findings presented here June 17th at the 8th International Congress of Parkinson's Disease and Movement Disorders.

"This treatment was tolerated as well as it is in younger patients with other conditions," said principal investigator Joseph Jankovic, MD, Professor of Neurology, Baylor College of Medicine, Director, Parkinson's Disease Center and Movement Disorders Clinic. Houston, Texas. "Further studies will be necessary in order to determine the proper dosage."

Dr. Jankovic and colleagues wanted to see if topiramate effective in addressing essential tremor because the current treatment options, primarily propranolol and primidone, are limited by adverse effects and long term tolerance. Topiramate has widespread use as an anticonvulsant, and data show that it has neurostabilizing activities at multiple receptors and ion channels, including the gamma-aminobutyric acid (GABA) receptors as well as the amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate glutamate receptors, Dr. Jancovic said.

They were encouraged about earlier research showing that people with essential tremor might respond to topiramate at a dose of 400 mg per day and therefore designed the current research, a double-blind, placebo-controlled study. The 223 patients were 18 to 80 years old and had essential tremor as defined by Tremor Investigational Group diagnostic criteria. The study design required that they have either moderate to severe posture tremor or tremor in the upper extremity triggered by either action or intention.

Patients were allowed to receive one concomitant anti-tremor agent at a stable dosage throughout the study. After randomization to treatment or placebo, the dose in the treatment arm was titrated over 12 weeks to the dose at which tremor resolved or to the patients' maximum tolerated dose, up to a maximum of 400 mg/day. Patients continued at that dose during the12-week maintenance phase.

There were 117 patients in the treatment group and 106 in the placebo group; 108 in the treatment group and 100 in the placebo group had at least 1 on-treatment efficacy assessment. Patients were an average of 62 years old, and half were not receiving an anti-tremor medication when they entered the study.

The investigator scored tremor with the Fahn-Tolosa-Marin Tremor Rating Scale (TRS), which has 3 subscales -- tremor location and severity; specific motor tasks and function, and functional disabilities. Because the subscales involved different numbers of test items, the investigators used the total normalised TRS score or the sum of the mean normalized subscores as the primary efficacy measure.

The average topiramate dose during maintenance was 292 mg daily. The total normalised TRS scores were improved 29% from baseline in the topiramate group and 16% in the placebo group (P =.0003). Improvements in scores that favored topiramate over placebo had a tendency toward significance for tremor location and severity (P =.06). The differences in score between groups for the other 2 subscales showed topiramate was significantly more effective than placebo (P <.001).

The between-group differences in the Patient and Investigator Global Assessments were significantly in favor of topiramate (P <.001). Among patients, 72% rated tremor control as good or very good in the topiramate group as did 69% of the investigators. The rates in the placebo group were 15% for subjects and 20% of investigators.

Adverse events caused 32% of topiramate patients and 10% of placebo group to discontinue treatment. The most common adverse events were paresthesia, weight loss, taste perversion, memory difficulty, fatigue, nausea, appetite decrease, and somnolence.


[Presentation title: "A multicenter, double-blind, placebo-controlled trial of topiramate in essential tremor." Abstract #P1314]

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