Clinical Question: Is topiramate (Topamax) effective in the treatment of essential tremor?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: In this study, 223 patients with essential tremor were randomly assigned to receive topiramate or matching placebo. The topiramate was initiated at 25 mg per day and increased weekly to a target dosage of 400 mg per day or until the tremor resolved. Once at the maximum dose, the patients maintained it for an additional 12 weeks.

Staff unaware of treatment assignment assessed the severity (amplitude) of tremors, the ability to perform specific tasks (e.g., writing, drawing, pouring liquids), and patient-reported functional problems (e.g., speaking, eating, dressing). These were combined into an overall scale and individual subscales that were evaluated by intention to treat.

A large proportion of patients withdrew from the study (38 percent taking topiramate and 22 percent taking placebo; number needed to harm = 6; 95% confidence interval, 4 to 21), mainly because of side effects. The median duration of the study was five months. Although patients taking topiramate experienced improvement on the overall tremor scale and on the functional scales, so did the patients taking the placebo. The mean changes on these scales were 9.4 to 12.7 in the treatment group and 3.7 to 8.9 in the placebo group. Generally, a 15- to 20-point difference on a 100-point scale is clinically important; none of the results met this threshold.

Bottom Line: Topiramate is slightly better than placebo in reducing tremor and improving function in patients with essential tremor. In this study, the differences do not appear to be clinically significant. Given the expense and the study’s significant drop-out rate because of side effects, topiramate is not recommended as a first-line treatment. (Level of Evidence: 1b)