Dovepress Overview of essential tremor 11 patients with ET.55 At the end of the 4-week treatment period, only two patients experienced objective or subjective change in their tremor. tremor compared to baseline in a blinded, controlled study.65 Another study failed to show any improvement in tremor, but had a 60% dropout rate due to side effects.66 Antidepressants Antidepressants have not been used to treat ET with much success. One small study failed to find any reduction in clinical ratings of tremor with mirtazapine (Remeron), an antagonist of α-2, 5HT2, and 5HT3 receptors.56 Trazodone (Desyrel) is a serotoninergic agonist that has been evaluated in two double-blind, randomized, placebo-controlled studies.57,58 Both studies failed to find any improvement in tremor evaluations based on clinical rating scales. Antipsychotics Clozapine (Clozaril) is an atypical neuroleptic with minimal extrapyramidal side effects that has been shown to reduce tremor by 45%–50% in two controlled studies.59,60 However, clozapine use has a 1% risk of agranulocytosis, a serious side effect, and its use should be reserved for refractory cases. Weekly white cell counts are required for the first 6 months of therapy and every other week thereafter. Limited evidence is available to determine the utility of olanzapine (Zyprexa) and quetiapine (Seroquel) in reducing tremor. Antivirals Amantadine (Symmetrel) is an antiviral medication that is used to treat PD. A double-blind, cross-over, placebo-controlled trial evaluated amantadine (200 mg/day) in 16 patients with ET.21 After 15 days of treatment tremor measures were not reduced compared to baseline in the amantadine group. Over one-third of patients experienced increased postural tremor. Barbituates Two double-blind, randomized, placebo-controlled crossover studies evaluated the effects of phenobarbital, an anticonvul- sant and sedative, on tremor. One study found a significant improvement in accelerometry parameters compared to placebo61 but no change in clinical rating scales. The other study failed to find a difference compared to placebo.62 Benzodiazepines Alprazolam (Xanax) has been shown to reduce clinical rat- ings of tremor in two double-blind, randomized, controlled studies.63,64 Although alprazolam has demonstrated effect in some patients with ET, it should be used cautiously as it has a high potential for abuse. Clonazepam (Klonopin) improved Neuropsychiatric Disease and Treatment 2010:6 Bronchodilators Studies of theophylline (Theo-dur), a xanthine derivative bronchodilator on ET, have found conflicting results. One blinded study of a single oral dose of theophylline evaluated changes in tremor over a 24-hour period and found no change as measured by volumetric methods (the volume of water subjects spilled from a cup held in a flexed position for 60 seconds). However, after 3 weeks of treatment with theophylline, tremor was significantly improved using clini- cal rating scales.67 Another blinded study found a reduction in tremor after 4 weeks of treatment compared to placebo.68 Carbonic anhydrase inhibitors Controlled studies of two carbonic anhydrase inhibitors, acetazolamide (Diamox) and methazolamide (Glauctabs, Neptazane), failed to find a significant difference in tremor evaluations compared to placebo.69,70 Treatment considerations for pharmaceutical agents Both propranolol and primidone have substantial evidence supporting their effects in reducing symptoms of ET although approximately 30% of patients will not respond to either of these agents. As initial therapy, primidone and propranolol have shown similar efficacy and the choice of which agent to use primarily depends upon a patient’s comorbid condi- tions and tolerability to either agent. Both medications have shown efficacy for at least 1 year,69,70 although there is some evidence for a reduction in tremor control over time with both medications and a dose increase may be necessary. Botulinum toxin Chemodenervation using botulinum toxin A (BTX) has been demonstrated to modestly reduce hand tremor in patients with ET, but its use is hampered by side effects including hand weakness. One randomized, double-blind, placebo- controlled study evaluated the effects of 50 U and 100 U of BTX on limb tremor in 133 patients over a 16-week period.73 BTX doses were injected as 15 U into each of the flexor carpi radialis and ulnaris and 10 U into each of the extensor carpi radialis and ulnaris in one group, and 30 U into each of the flexor carpi radialis and ulnaris and 20 U into each of the extensor carpi radialis and ulnaris for the submit your manuscript | www.dovepress.com Dovepress 405