Zesiewicz et al First-line pharmacologic agents used to treat ET are pro- pranolol and primidone, although other medications including sotalol, atenolol, alprazolam, and topiramate have also been shown to provide tremor reduction.34 In cases of refractory tremor, a reversible, surgical procedure called deep brain stimulation (DBS) into the thalamus may effectively treat tremor. Antihypertensive medications Beta blockers and calcium channel blockers are medications that are commonly used to treat hypertension and other cardiovascular conditions. Propranolol (Inderal) is a nonse- lective beta-adrenergic receptor antagonist that effectively treats tremor and is the only medication that is FDA-approved for the treatment of ET. The mean dose of propranolol in published, controlled trials was 185.2 mg/day. Propranolol is also available as a long-acting (LA) preparation with once daily dosing. Although this preparation has not been studied as extensively as the immediate formulation, evidence from two clinical studies suggests that it reduces tremor in patients with ET.35,36 Other antihypertensive medications, including atenolol (Tenormin) and sotalol (Sotacor) have been shown to reduce ET compared to placebo.37,38 One study compared atenolol to other beta blockers (sotalol and propranolol) and found that atenolol had a lower magnitude of effect than either of the other agents.37 There is also limited evidence that nadolol (corgard) and nimodipine (nimotop) may treat ET.39,40 One study of nadolol compared tremor responders to non- responders and observed that only patients who previously responded to propranolol experienced significant tremor reduction from nadalol.39 Verapamil (Calan) and nifedipine (Adalat) have not been shown to reduce tremor in controlled studies.41 Studies of clonidine (Catapress), flunarizine (Sibelium), metoprolol (Lopressor/Toprol), and nicardipine (Cardene) were either limited or produced conflicting results, and their potential use in treating tremor remains uncertain. Antiepileptics Primidone (Mysoline) is an anticonvulsant that effectively treats ET. Studies using accelerometry and clinical rating scales have demonstrated approximately a 50% reduction in tremor magnitude with the use of primidone, making it a first-line treatment in patients with ET.34 Primidone is associated with frequent adverse events including sedation, nausea, vertigo, and an acute toxic reaction which are usu- ally more severe soon after treatment initiation.34 A lower 404 submit your manuscript | www.dovepress.com Dovepress Dovepress initial dose and slower titration has not been shown to reduce adverse effects compared to an initial dose of 25 mg per day and increasing by 25 mg every 4 days.42 Gabapentin is an anticonvulsant with a structure similar to gamma-aminobutyric acid (GABA) and is approved as adjunctive therapy for partial seizures. One study found that gabapentin reduce tremor when used as monotherapy in doses of 1,200 mg/day (n = 16), with a 77% improvement in tremor as measured by accelerometry at day 15.43 However, while gabapentin was found to treat ET in a small number of trials as monotherapy, it has not shown efficacy as adjunc- tive therapy.44,45 Topiramate (Topamax) is an anticonvulsant that has been shown to effectively reduce ET.45–48 A large randomized, multicenter, double-blinded, placebo-controlled study found that patients treated with topiramate had a 29% improvement in the FTM rating scale score compared to a 16% improve- ment in the placebo-treated patients (P , 0.001).48 The aver- age mean dose of topiramate in the study was 292 mg/day, although the between-group difference was significant (P , 0.01) at 4 weeks for a topiramate dose of 62 mg/day. Side effects were more common in the topiramate group, and included paresthesia, weight loss, taste abnormalities, memory difficulty, and appetite suppression. Zonisamide (Zonegran) is an anticonvulsant that may have antitremor efficacy, although study results are mixed. One controlled study found that zonisamide improved ET compared to arotinolol, an antihypertensive agent with mixed alpha and beta-blocking action.50 However, at least one addi- tional study failed to find significant antitremor efficacy from zonisamide and a 30% drop-out rate due to adverse events including fatigue, diarrhea, and headache. Levetiracetam (Keppra), a pyrrolidine derivative with strong specific binding to cerebellar receptors, failed to show significant tremor reduction when tested for several weeks compared to placebo in several controlled trials.42,51,52 Pregabalin (Lyrica): the effect of pregabalin on ET is unclear. One randomized, double-blinded, placebo-controlled trial of 22 patients with ET found a significant reduction in tremor amplitude in patients treated with pregabalin group at a mean dose of 286 mg/day.53 However, another controlled trial of 20 ET patients failed to find improvement in tremor rating scale scores in patients taking pregabalin.54 Antibiotics Isoniazid, an antituberculosis medication, was evaluated in a double-blind, randomized, placebo-controlled study of Neuropsychiatric Disease and Treatment 2010:6