A new evidence-based guideline issued by the American Academy of Neurology for the treatment of essential tremor reinforces the use of propranolol and primidone as the go-to agents for the disease.
However, these first-line agents – used as monotherapy or combination therapy since the 1980s – do not work in between 30% and 50% of people with essential tremor (ET).
Moreover, a 2010 study of 223 ET patients in a clinical database revealed that more than half of patients taking primidone and/or propranolol had discontinued them, suggesting that the need for alternatives is great (Parkinsonism Relat. Disord. 2010;16:604-7). Primidone and propranolol are known to cause side effects at higher titrations.
Essential tremor is a common, progressive neurological disease, formerly called "benign essential tremor," that causes a rhythmic trembling of the hands, head, voice, legs, or trunk, and is sometimes mistaken for Parkinson’s disease.
In its new ET guideline, published online Oct. 19 in the journal Neurology as an update of its 2005 guideline for ET, the AAN continues to recommend topiramate, alprazolam, atenolol, gabapentin, and sotalol as second-line treatments, based on clinical evidence that they are probably effective. The AAN’s new recommendations are based on reviews of 589 articles (252 of these complete reviews) of randomized controlled trials, observational studies, cohort studies, and case series published between 2004 and 2010 (Neurology 2011 Oct. 19 [Epub ahead of print]).
The AAN’s team of reviewers, led by Dr. Theresa A. Zesiewicz of the University of South Florida in Tampa, found that they could not recommend levetiracetam and 3,4-diaminopyridine as second-line agents, based on quality (Level B) clinical evidence that they do not reduce limb tremor. The evidence on flunarizine suggests that it is probably ineffective in reducing limb tremor. And the reviewers could not recommend pregabalin, zonisamide, and clozapine, based on insufficient evidence to support or refute their use in ET.
"What's important to understand is that essential tremor may be a heterogeneous condition."
"There were some agents we had some hopes for that didn’t pan out, and levetiracetam was one of them," Dr. Zesiewicz said in an interview, adding that patients not responding to primidone or propranolol, or in whom these are contraindicated, might benefit from any of the currently recommended second-line agents with level B evidence supporting them. Of these, she said, topiramate is supported by the largest cohort studies, but "any of the level B, or level C agents" can be tried. Surgical interventions in ET patients, though seen to have greater treatment effect than medications, are seldom tried before a second-line agent doesn’t work and a tremor becomes debilitating.
"The reason we don’t go to [surgery] right away is because when the side effects do occur – which is relatively rare – they can be serious," Dr. Zesiewicz said.
The guideline’s advice on surgical interventions for ET remain unchanged from 2005, with deep brain stimulation (DBS) still recommended. DBS, by which a device is implanted in the brain to transmit electrical impulses, "has really become the surgery of choice," Dr. Zesiewicz said.
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