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Practice Guidelines

AAN Updates Guideline on Treatment of Essential CARRIE ARMSTRONG

However, a placebo effect could not be ruled Guideline source: American Academy of Neurology out, and therefore, the AAN found insuf- Evidence rating system used? Yes ficient evidence to support or refute the Literature search described? Yes effectiveness of olanzapine in the treatment of . Guideline developed by participants without relevant financial One randomized crossover study of leve- ties to industry? No tiracetam evaluated the short-term effects Published source: Neurology, November 2011 of a single dose on limb tremor with only Available at: http://www.neurology.org/content/early/2011/10/18/ limited clinical benefits. Two randomized, WNL.0b013e318236f0fd.full.pdf+html crossover, lower-quality studies showed no benefit of in patients with essential tremor. Coverage of guidelines and (Mysoline) are the was evaluated in two stud- from other organizations most commonly used therapies for essential ies. One was a randomized, parallel-group, does not imply endorse- ment by AFP or the AAFP. tremor, but these agents are ineffective for up double-blind, placebo-controlled trial to one-half of patients. In 2005, the American involving 22 patients. Pregabalin was started A collection of Practice Guidelines published in Academy of Neurology (AAN) published rec- at a dosage of 50 mg per day and titrated by AFP is available at http:// ommendations for the use of other therapies 75 mg per day every four days to a maximum www.aafp.org/afp/ for essential tremor. Although no new data of 600 mg per day. A significant reduction in practguide. have been published for many of the drugs tremor amplitude was observed at a mean included in the 2005 guideline, results from dosage of 286 mg per day. Improvements studies on (Topamax), olanzapine in action tremor limb scores on the Fahn- (Zyprexa), levetiracetam (Keppra), pregabalin Tolosa-Marin Tremor Rating Scale were also (Lyrica), zonisamide (Zonegran), and clo- noted. The second trial was a randomized zapine (Clozaril) are now available. Based on crossover study involving 20 patients who these results, the AAN has changed some of its received 150 to 600 mg of pregabalin per recommendations for these agents (Table 1). day, titrated over six weeks, or placebo. No Several new studies have addressed the improvements on the Tremor Rating Scale effectiveness of topiramate in the treatment were noted in the treatment group, and of essential tremor. The results of these stud- quality of life scores were significantly lower. ies confirmed those of previous studies, Based on the results of these two trials, the which showed that topiramate is an effective AAN determined that there is insufficient treatment. Therefore, no change was made to evidence to support or refute the effective- the 2005 recommendation that topiramate ness of pregabalin in the treatment of essen- should be considered for patients with essen- tial tremor. tial tremor. The antiepileptic agent zonisamide was The atypical antipsychotic olanzapine was evaluated in several lower-quality stud- compared with propranolol in one small ies. One of the studies was a double-blind, crossover study. A total of 38 patients were placebo-controlled, randomized trial involv- randomized to receive 20 mg of olanzapine ing 20 patients who received a mean dosage per day or 120 mg of propranolol per day. of 160 ± 50 mg of zonisamide per day. No sig- Both drugs significantly reduced scores on nificant improvements were observed on the all evaluation measures after one month. Tremor Rating Scale, but tremor amplitude

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Table 1. Effectiveness of Therapies for Essential Tremor

Effective; should be offered Unknown effectiveness Primidone (Mysoline) Amantadine Propranolol Clonidine (Catapres) Probably effective; should be considered (Clozaril) Alprazolam (Xanax)* adjunct therapy Atenolol (Tenormin) Gamma knife thalamotomy Gabapentin (Neurontin) monotherapy L-tryptophan/pyridoxine Propranolol for head tremor Metoprolol (Betapace) (Cardene) Topiramate (Topamax) Olanzapine (Zyprexa) (Trileptal) Possibly effective; may be considered (Klonopin)* Pregabalin (Lyrica) Deep brain stimulation of the ventral intermediate thalamic nucleus (in refractory cases) Quetiapine (Seroquel) Nadolol (Corgard) Sodium oxybate (Nimotop) Thalamic deep brain stimulation for head and voice tremor OnabotulinumtoxinA (Botox) Theophylline Unilateral thalamotomy (in refractory cases) (Gabitril) Not effective or probably not effective; Zonisamide (Zonegran) not recommended Isoniazid Levetiracetam (Keppra) Methazolamide (Neptazane) Mirtazapine (Remeron) (Procardia) Pindolol Trazodone

*—Because of abuse potential, use caution when considering use. significantly improved in the treatment treatment in the initial phase. The AAN group compared with baseline. The other found insufficient evidence to support or study found significant improvements on refute the effectiveness of clozapine for the Tremor Rating Scale in patients who long-term use in patients with essential received zonisamide. Based on the results tremor. ■ of these studies, the AAN determined that there is insufficient evidence to support or refute the effectiveness of zonisamide in the Answers to This Issue’s CME Quiz treatment of essential tremor. Q1. B Q6. A, B, C, D The antipsychotic clozapine was down- Q2. B, C Q7. D graded based on the results of a trial that Q3. A, B, C Q8. A, D evaluated the short-term effects of the drug Q4. B Q9. A, B, C, D in a controlled setting, followed by a open- Q5. B Q10. A, B, D label phase in patients who responded to

August 1, 2012 ◆ Volume 86, Number 3 www.aafp.org/afp American Family Physician 293