The American Academy of Neurology updates its recommendations on the use of levetiracetam, 3,4-diaminopyridine, flunarizine, pregabalin, zonisamide, and clozapine to treat essential tremor.
Levetiracetam and 3,4-diaminopyridine “should not be considered” and flunarizine “may not be considered” as treatments for limb tremor in patients with essential tremor, according to a guideline update from the American Academy of Neurology (AAN) published in the October 19 online Neurology. The effectiveness of pregabalin, zonisamide, and clozapine as essential tremor treatments is unknown, the investigators added.
Theresa A. Zesiewicz, MD, Movement Disorders Professor at the University of South Florida in Tampa, led an AAN Quality Standards Subcommittee in updating the academy’s 2005 practice parameter on essential tremor treatment. Dr. Zesiewicz and colleagues reviewed 589 articles (252 of them in their entirety) for their evidence-based guideline update.
Levetiracetam and 3,4-diaminopyridine “probably do not reduce limb tremor in essential tremor and should not be considered (Level B),” the subcommittee found. Although one Class I study found that levetiracetam treatment was associated with some improvement in line drawing in patients with essential tremor, two Class II randomized, crossover studies found that it led to no significant improvements in such patients. Similarly, a Class I study found no benefit in essential tremor from 3,4-diaminopyridine treatment.
“Flunarizine possibly has no effect in treating limb tremor in essential tremor and may not be considered (Level C),” according to the subcommittee. Two Class III studies using blinded video analyses found that the drug was ineffective.
There is “insufficient evidence to support or refute the use of pregabalin, zonisamide, or clozapine as treatment for essential tremor (Level U),” Dr. Zesiewicz and colleagues added. Although one Class II study found that pregabalin reduced tremor amplitude and improved action tremor limb scores among patients with essential tremor, another found that it resulted in worse quality of life and no improvement in tremor measures. Similarly, one Class III study linked zonisamide to significant improvements on the Fahn-Tolosa-Marin Tremor Rating Scale, but another found no such improvements (despite significant improvement in tremor amplitude). Clozapine was downgraded to insufficient evidence status because of a trial on the drug’s acute effects in a controlled setting.
The update reaffirmed many of the 2005 practice parameter’s recommendations. As in the previous guideline, propranolol and primidone were classified as “effective” treatments for essential tremor. Alprazolam, atenolol, gabapentin monotherapy, sotalol, and topiramate were classified as “probably effective” treatments. Nadolol, nimodipine, clonazepam, botulinum toxin type A, deep brain stimulation, and thalamotomy retained their status as “possibly effective” treatments. In addition, the effect of gamma knife thalamotomy on essential tremor remains Level U, according to Dr. Zesiewicz and colleagues.
Most of the treatments that retained their former status have not been studied by trials rated better than Class IV since 2005, the subcommittee explained. However, it added, several new Class II studies confirmed that topiramate is an effective treatment for essential tremor.
Dr. Zesiewicz and colleagues called for controlled clinical trials of additional drugs for essential tremor, using such standardized outcome measures as disability scales and cost-benefit analyses. However, they noted, future research could be complicated by the possibility that the brains of people with essential tremor undergo a heterogenous set of degenerative changes, as suggested by recent findings. “Essential tremor is likely to be a syndrome or family of diseases rather than a single disease,” according to the subcommittee. “Furthermore, the sequence of molecular events that underlie these degenerative changes has yet to be elucidated, and until such a time, it will be difficult to design specific targets for pharmacotherapeutic intervention.”