Essential Tremor

 

It can occur gradually: a trembling or up-and-down shaking of the hand. An uncontrolled movement which worsens as the most basic movements, such as holding a cup of coffee, writing or using a knife and fork are attempted. It can worsen over time and involve your whole arm or both arms. Invovlement of your head and your voice can occur as well.

This problem is called Essential Tremor. It is the most common type of "shaking disorder", and frequently occurs in middle-aged or older persons. The exact cause of this disorder remains unknown.

Despite being referred to as essential tremor a benign disorder, this problem can result in significant emotional distress. There is no reason to panic.

Many people relate all shaking disorders as Parkinson's disease. This is not true for the vast majority of cases. Essential tremor does not indicate a more serious underlying illness. These tremors can be controlled with treatment in many cases.

As you age, the risk of developing essential tremor increases. Though the exact cause is not completely understood, genetics may play a role. About half of the cases of essential tremor run in families. This genetic influence is sporadic, however.

How it progresses

Essential tremor often begins gradually. Sometimes it first appears in the teen years, goes into remission for decades and surfaces again late in adulthood. Many people associate their tremor with a stressful event such as an accident or the death of a loved one. Although not a cause of essential tremor, stress may call attention to it.

Essential tremor usually involves the hands, arms and chin. The tongue, larynx and eyelids are less commonly involved. Jerky movements begin immediately or soon after the start of a voluntary action such as eating or writing. If you have essential tremor, coordinated movements such as touching your nose or touching someone else's fingertip become difficult. Anxiety aggravates the problem. Trying to stop the tremor only makes it worse. Frustrated, many people with essential tremor dread social and business gatherings and even sexual activity. Symptoms can fluctuate by the hour or over longer periods. The problem does not occur during sleep.

A link to Parkinson's disease?

People with essential tremor may be misdiagnosed as having more serious problems such as Parkinson's disease. Essential tremor does not indicate parkinsonism. However, 5 percent to 10 percent of people with essential tremor eventually develop Parkinson's disease. Here are some key differences between essential tremor and Parkinson's disease:

Tremor Scale (symptomatic complaint of tremor in any part of the body)

 0

 Absent (no tremor or writing impairment)

1 

Slight and infrequently present (mild tremor, writing, and drawing of spiral minimally impaired)

 2

Moderate; bothersome to most patients (writing and drawing of spiral moderately impaired)

3 

Severe tremor (writing and drawing severely impaired; interferes with many activities such as drinking liquids)

 4

Marked tremor (interferes with most activities)

Treatment Options

Once the diagnosis is established and functional disability is reported, treatment options can be considered. Medications used to treat essential tremor include:

.

Propranolol (Inderal®):
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 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. The LA or Long Acting preparation allows easy once daily dosing and improves compliance. 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.

Inderal or Inderal LA has long been the mainstay of tremor therapy. Recently the generic brand long acting medications have become unavailable. However, the brand or dispense as written (daw) LA is easy to use as a once daily dose and is available in 60mg, 80mg, 120mg and 180mg strength and can be increased to >300 mg/day. It is imperative that blood pressure and pulse be monitored during doseage escalation. Other non-selective beta-blockers can be used as the first treatment option (nadolol, lopressor) if prescription plans will not cover brand Inderal LA.

Primidone (Mysoline®):
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.

Drug Tolerance:
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.

Second-line drug therapies for the treatment of ET include benzodiazepines, a class of drugs that interferes with chemical activity in the nervous system and brain, serving to reduce communication between nerve cells and to a "slowing down" the central nervous system. Such medications promote sleep, relieve anxiety, reduce restlessness, and relax muscles. Examples of benzodiazepines that have been used to treat patients with ET include clonazepam (Klonopin®), lorazepam (Ativan®), alprazolam (Xanax®), and diazepam (Valium®).

Nadolol (Corgard®) is a nonselective, beta-adrenergic receptor antagonist that is similar to propranolol. It may be an effective treatment for individuals with ET who were previously responsive to propranolol. Since propranolol and inderal LA have recently been unavailable, use of nadolol has increased accordingly. The medication is available in 20mg, 40mg, and 80mg tablets. Metoprolol (Lopressor) is available in scored 50mg and 100mg tablets.

Methazolamide (Neptazane®) has been studied and seems to have extremely limited effectiveness in the treatment of essential head and voice tremor. Side effects may include drowsiness, nausea, stomach discomfort, paresthesias, or loss of appetite. The drug gabapentin (Neurontin®) has also been studied in a double blind, controlled trail for its effectiveness in the treatment of ET. The results suggested that, as an adjuvant therapy, gabapentin has limited benefit in patients with ET.

Mirtazapine (Remeron) is a tetracyclic antidepressant. This medication has recently been reported to be helpful in the treatment of tremor. The mechanism of action of this medication is unknown. Evidence from preclinical studies suggests enhancement of central noradrenergic and serotonergic activity by acting as an antagonist at central presynaptic alpha-2 adrenergic inhibitory autoreceptors and heteroreceptors. In addition, mirtazapine is a potent receptor antagonist of the following: both 5-HT2 and 5-HT3 (serotonin) receptors, H1 (histamine) receptors, peripheral alpha-1 adrenergic receptors, and muscarinic (anticholinergic) receptors. Remeron has only recently been reported to be effective in the treatment of tremor. This medication was noted to be effective and safe. Clinical antidepressant effect was also noted. This medication is available in 15mg, 30mg, and 45mg tablets. The tablets are scored and can be started as 7.5mg and increased as needed or tolerated. The dose reported to be effective for tremor was 30mg. Side effects, according to the PDR, rarely include agranulocytosis, fatigue, dizziness, weight gain, and abnormal liver function tests.

Selected patients with ET who do not respond to drug therapy may receive local injections of botulinum toxin (BTX) type A (BOTOX®). Some improvement in symptoms has been noted. Chemodenervation with BTX may significantly ameliorate essential hand tremor in patients who fail to improve with conventional pharmacologic therapy.

For severe cases that don't respond to medication options surgical treatment can be offered.

There is no one best single treatment. Stimulants such as caffeine should be avoided. Tiny amounts of alcohol (red wine) may reduce the difficulty from the tremor. In general, alcohol is not a recommended form of treatment.

Nondrug therapy options include exercises with light (1- or 2-pound) weights strapped to the wrist to try to promote hand stability.

Tremor can be both annoying and worrisome. If you or someone you know have a tremor, seek help. It is not a "mental problem" or "a part of aging." A full range of activities with appropriate treatment can still be enjoyed. An accurate diagnosis is essential for long term prognosis, treatment and optimal daily living.

 

Page adapted from: We Move & Mayo Foundation for Education & Research Web Sites