New AAN Guideline on Treating Essential Tremor

Megan Brooks

October 19, 2011

October 19, 2011 — The American Academy of Neurology has released an update of their 2005 practice parameter on the treatment of essential tremor (ET). It includes 3 key changes to conclusions and recommendations from the previous guideline:

  • Levetiracetam and 3,4-diaminopyridine probably do not reduce limb tremor in ET and should not be considered (level B).

  • Flunarizine possibly has no effect in treating limb tremor in ET and may not be considered (level C).

  • There is insufficient evidence to support or refute the use of pregabalin, zonisamide, or clozapine as treatment for ET (level U).

The update is based on a review of relevant research published since 2005 and appears in the October 19 online issue of Neurology. It is endorsed by the International Essential Tremor Foundation. Theresa A. Zesiewicz, MD, from the University of South Florida in Tampa, led the team of experts who developed the update.

Changes Not Surprising

In a telephone interview with Medscape Medical News, Professor Gunther Deuschl, MD, from Christian Albrechts University in Kiel, Germany, and president of the Movement Disorder Society, said there is "nothing really surprising" in the update.

"Levetiracetam is one of the new antiepileptics, and they are always candidates for treating tremor, but unfortunately, it turns out that it doesn't work for [ET]," he noted.

"The 3,4-diaminopyridine has had quite a good history because there is a physiology behind it, and it works for oscillations (tremor) of the eyes, but it doesn't work for the extremity tremor, and not for ET," Dr. Deuschl commented.

"Flunarizine is an old drug with level C evidence because there really is no good evidence, but also because the studies are very small," he added. Dr. Deuschl was not involved in the guideline update.

Propranolol, Primidone Still Mainstays

The new guideline states that propranolol and primidone continue to be the most effective treatments for ET (level A evidence, established as effective), and propranolol is currently the only medication approved by the US Food and Drug Administration to treat ET, the authors note.

Still, not all patients improve on or tolerate propranolol or primidone; 30% to 50% of patients will not respond to either agent. "These first-line medications for ET clearly fail to meet the needs of many patients," the authors write.

The update also states that alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are probably effective for ET (level B evidence). This remains unchanged from 2005.

Nadolol, nimodipine, clonazepam, botulinum toxin A, deep brain stimulation (DBS), and thalamotomy remain at level C evidence (ie, possibly effective). There is currently insufficient evidence (level U) on the value of gamma knife thalamotomy, the guideline states.

DBS Helpful in Severe Tremor

"There is clearly a need for better treatments and more research," Dr. Deuschl told Medscape Medical News. "When it comes to [ET], unfortunately, there is really not much new going on," he said.

DBS is "one of the best treatments for severe tremors; the potency of propranolol and primidone is about 50% tremor reduction, while the potency of [DBS] is about 90%," he said.

"What is really sad, however, is there is no double-blind study on DBS for [ET]. We need a clear demonstration that for the worst cases this is really a good treatment. That needs to be urgently done," Dr. Deuschl said.

In their report, Dr. Zesiewicz and colleagues note that the pursuit of better treatments for ET is "hampered by our limited understanding of the pathophysiology of ET."

They point out that some recent postmortem evidence suggests the presence of a heterogeneous set of degenerative changes in the brains of people with ET. This indicates that ET is "likely to be a syndrome or family of diseases rather than a single disease, which adds a layer of complexity to matters," they say.

The guideline update was funded by the American Academy of Neurology. No author received honoraria or financial support to develop the guideline. Dr. Zesiewicz serves on the speakers' bureau for and has received funding for travel and speaker honoraria from Teva Pharmaceutical Industries Ltd; serves on the editorial board of Tremor and Other Hyperkinetic Movement Disorders; serves/has served as a consultant for Boehringer Ingelheim, Teva Pharmaceutical Industries Ltd, Allergan Inc, UCB, and Novartis; is listed as an inventor on a provisional patent on the use of nicotinic modulators in treating ataxia and imbalance held by the University of South Florida; and receives/has received research support from Pfizer Inc, the National Ataxia Foundation, the Friedreich's Ataxia Research Association, and the Bobby Allison Ataxia Research Center. A complete list of disclosures for guideline authors is listed with the original article. Dr. Deuschl has no relevant disclosures concerning tremor.

Neurology. Published online October 19, 2011.


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