Essential Tremor Medication

Updated: Feb 24, 2023
  • Author: Natalya V Shneyder, MD; Chief Editor: Selim R Benbadis, MD  more...
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Medication

Medication Summary

Beta-adrenergic blockers (principally propranolol) and primidone are the first-line treatments for essential tremor. Each provides good benefit in 50–70% of cases and neither has been demonstrated to be unequivocally superior to the other. Adverse effects are more prominent early in treatment with primidone but are more prominent later in treatment with propranolol. Starting with propranolol is preferable in younger individuals, and primidone is commonly started first in older patients.

Patients who require medication treatment are usually started on one of these medications. The drug is introduced at a low dose and is increased slowly until complete response, intolerability, or usual maximum dose is attained. If some benefit is achieved but is incomplete, the other medication may be added, and slowly increased in an effort to achieve maximum benefit. Treatment with both drugs has been shown to be effective in patients who have had an insufficient response to one. Patients should not expect complete resolution of symptoms.

More evidence exists to support effectiveness in upper extremity tremor than in head or lower extremity tremor. A decrease in tremor amplitude is the usual response, although some evidence indicates that primidone may decrease tremor frequency as well.

For patients who do not achieve an adequate response with primidone and propranolol, the authors try topiramate. Gabapentin and clonazepam may also be tried. 

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Beta-Blockers, Nonselective

Class Summary

The mechanism of action in the reduction of essential tremor is not known. The action is hypothesized to be mediated primarily by peripheral beta2 adrenoreceptors, but some evidence indicates that beta1-receptor antagonists such as metoprolol also have some efficacy. Peripheral beta2 adrenoreceptors are located in the extrafusal muscle fibers and on the intrafusal fibers of the muscle spindles.

Propranolol hydrochloride (Inderal, InnoPran XL)

Propranolol, 1 of 2 medications of choice for essential tremor, has been shown to be effective in double-blind, placebo-controlled trials. It is a nonselective beta-adrenergic blocker with negative inotropic, chronotropic, and dromotropic properties. Propranolol is lipophilic with central nervous system (CNS) effects. Its mechanism of action is probably related to peripheral beta2 antagonism. The drug's long-acting formulation has efficacy similar to that of the standard formulation and may allow fewer daily doses.

In general, beta1-receptor antagonists are more effective than placebo but are not as effective as beta2-receptor antagonists. Metoprolol, a relatively selective beta1-receptor antagonist, may be useful in patients with asthma and other pulmonary conditions. May be used as monotherapy or in combination with primidone.

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Anticonvulsants, Other

Class Summary

Some agents in this class have demonstrated tremor-suppressing effects. Their mechanism of action is unknown, but it presumably involves the CNS.

Primidone (Mysoline)

Primidone is metabolized to phenobarbital and PEMA. It has tremor-suppressing activity independent of plasma concentrations of phenobarbital and is thought to be superior to phenobarbital. PEMA is not tremorolytic. Primidone is believed to have an independent mechanism for its effect on tremor.

It is strongly recommended that treatment with primidone be initiated with low doses because adverse effects at initiation of treatment are common. Start with one quarter or one half of a 50-mg tablet at bedtime and increase the dose slowly every week. Alternatively, introduce primidone using a 250 mg/5 mL suspension. Start with 1 drop at bedtime and increase the dose by 1 drop each night for 20 nights. Then convert the patient to a 50-mg tablet and increase the dose slowly every week.

For patients who initially respond to primidone but later develop a tolerance to it, increasing the dose to as high as 1000 mg/day in an effort to regain benefit is advisable.

Topiramate (Topamax, Qudexy XR, Topamax Sprinkle, Trokendi XR)

Topiramate's mechanism of action is unknown, but the blockage of voltage-dependent sodium channels and the augmentation of GABA are thought to play a role. Topiramate is not extensively metabolized and is excreted unchanged in the urine.

Clonazepam (Klonopin)

Benzodiazepines, particularly clonazepam, are commonly used in treating essential tremors, but their effectiveness is limited. Clonazepam may probably work to reduce anxiety, which can amplify tremor amplitude. May also enhance GABA activity. 

Gabapentin (Gralise, Neurontin)

Gabapentin, a membrane stabilizer, is a structural analog of the inhibitory neurotransmitter GABA, although it is thought not to exert an effect on GABA receptors. Appears to exert its action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gated calcium channels. May also modulate excitatory neurotransmitter release.

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