First-line drug therapies for the treatment of ET include...
The response of ET symptoms to treatment with the beta-blocker propranolol is highly variable. Beta-adrenergic blockers are a class of drugs that inhibit response to adrenergic stimulation by blocking Β-adrenergic receptors in heart muscle and other smooth muscle. Blockage of this stimulation effectively results in a decrease in in heart rate and cardiac output as well as a reduction in blood pressure. Approximately 50% to 70% of patients obtain some symptomatic relief. However, only in rare cases is the tremor totally suppressed. Beta-adrenergic blockage helps to control the involuntary, rhythmic movements of ET. Tremor amplitude is usually decreased; however, the frequency of tremor usually remains unaffected. The average reduction in tremor is about 50% to 60%. As the severity of the tremor lessens, functional disability also diminishes. However, some individuals will not respond to propranolol and the drug is often not well tolerated in older individuals.
The typical beginning oral dosage of propranolol is 40mg twice a day. The dosage may be gradually increased as needed to 120-320 mg/day in 2 to 3 divided doses. Propranolol and other beta-blockers may not be appropriate for patients with asthma, certain heart problems (e.g., advanced AV block, severe bradycardia, congestive heart failure, etc.), poorly controlled diabetes mellitus, pulmonary disease, or peripheral vascular disease (e.g., Raynaud's or Buerger's disease). Possible side effects of propranolol therapy include dizziness, fatigue, depression, diarrhea, nausea and vomiting, changes in blood sugar levels, or sexual difficulties. Other more serious side effects (particularly in susceptible patients with other preexisting medical conditions) may include difficulty breathing, sinus bradycardia, and hypotension.
Patients should not abruptly discontinue their treatment with a beta-adrenergic blocking agent such as propranolol. Physicians typically work with patients to establish a schedule of a gradual reduction in dosage. In this way, patients are slowly weaned from the medication. Because propranolol may interact with certain other drugs (e.g., anti-hyperglycemic and antihypertensive agents, barbiturates, NSAIDS, etc.), it is also important that the treating physician review the patient's current and recent past drug regimen.
Primidone, an anticonvulsant medication related to phenobarbital, slows the central nervous system and helps to reduce or control seizure activity in certain types of epilepsy. In addition, primidone is considered a first-line therapy for the treatment of patients with essential tremor. The starting dosage for primidone is low (e.g., 25 mg) and raised very slowly as needed. Two formulations of primidone are avialable; namely, 50mg and 250mg. Most clinicians recommend that patients start with half of a fifty tablet of primidone. The maximum dosage is 750 mg/day in three divided doses. However, 150 mg to 300 mg, in a single or divided doses appears to be an effective dose that may work as well as higher doses.
Six studies have been conducted to determine the rate of response to primidone. These studies reported varied rates ranging from a 60% to a 100% response. However, some patients will not respond to primidone therapy. One report estimated that about 71% of patients respond positively to primidone. Patients should not abruptly discontinue therapy with primidone. After consultation with a physician, the dosage is reduced gradually.
When treatment with primidone is initiated, some patients experience an acute idiosyncratic toxic response to the drug. Symptoms of this type of reaction may include nausea, vomiting, fatigue or sleepiness, confusion, and ataxia. This initial toxicity may occur in as many as 20% of patients. These symptoms typically resolve in one or two days.
Additional possible side effects of primidone include vertigo, unsteadiness, irritability, blurred vision, loss of appetite, or decreased sexual function. Primidone should be taken with meals to help minimize gastrointestinal (GI) effects such as indigestion and GI irritation. These side effects are typically short-lived and disappear with continued therapy. Side effects of chronic therapy are usually minimal and infrequent.
Some patients may develop a tolerance for propranolol and primidone over time, although no controlled studies have been conducted to support this view. However, propranolol and primidone are effective long-term therapy for some patients with ET. Acute adverse reactions to initiation of primidone therapy and side effects with chronic use of propranolol may hinder continued therapy in some patients.
Combination drug therapies:
Primidone and propranolol may be used in combination if they have not sufficiently reduced symptoms when used alone. In such cases, primidone is usually prescribed at 25mg at bedtime. The dosage is then increased gradually to 250 mg/day. Propranolol is then added to the drug regimen, usually at 40 mg three times per day. Propranolol dosage may be increased to a maximum of 320 mg/day if the response remains inadequate. Alternatively, a long-acting formulation of propranolol may be substituted if once-daily administration is desired. One study reported that the combination of propranolol and primidone was more effective in treating the symptoms of ET than the individual use of either drug.