eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Essential Tremor: Treatment & Medication

Author: Deborah A Burke, MD, Consulting Staff, Sub-investigator, Clinician, Movement Disorder/Parkinson's Disease Center, University of South Florida; Investigator, Physician, Roskamp Institute Memory Clinic
Coauthor(s): Robert A Hauser, MD, MBA, Professor of Neurology, Molecular Pharmacology and Physiology, Director, Parkinson's Disease and Movement Disorders Center, University of South Florida; Clinical Chair, Signature Interdisciplinary Program in Neuroscience; Theresa McClain, MSN, ARNP, Parkinson's Disease and Movement Disorders Center, University of South Florida
Contributor Information and Disclosures

Updated: Oct 26, 2009

Treatment

Medical Care

Primidone and propranolol are the cornerstones of maintenance medical therapy for essential tremor. These medications provide good benefit in reducing tremor amplitude in approximately 75% of patients.

For patients who require symptomatic therapy, one or the other of these medications is introduced at a low dose and increased slowly until sufficient benefit is achieved or the usual maximum dosage is reached (see Medication for dosing suggestions). If no benefit is derived, the medication is weaned and discontinued. If a partial benefit occurs, the other medication is added and slowly increased until sufficient benefit is achieved or the usual maximum dosage is reached. If no additional benefit occurs, this medication is then weaned and discontinued. Some patients require only intermittent tremor reduction, such as when attending a meeting or engaging in a social activity. For these patients, a cocktail or beer prior to the activity may be sufficient. An alternative is propranolol (10-40 mg) approximately one half hour prior to the event. Alcohol consumption is not an appropriate maintenance therapy for patients who seek tremor reduction throughout the day.

  • Alcohol
    • The mechanism of tremor reduction by alcohol is unknown. In a double-blind study, the 6-carbon alcohol methylpentynol did not have any effect on tremor. This suggests that the alcohol group of ethanol is not the element that provides antitremor activity and that the antitremor effect of ethanol is not due to sedation.
    • Restricted intra-arterial ethanol administration does not reduce tremor in the perfused limb. This suggests that effect of ethanol is mediated centrally.
  • Propranolol
    • Winkler first noted remarkable tremor reduction in a patient treated with propranolol for paroxysmal atrial tachycardia.
    • In a double-blind crossover study, propranolol at doses from 60-240 mg/d reduced tremor in 75% of patients with essential tremor. In a dose-response study, 240-320 mg/d was found to be the optimal dose range with no additional benefits above 320 mg/d.
    • Average tremor reduction is 50-60%, but some patients experience marked tremor reduction and others no benefit.
    • The mechanism of action probably is related to peripheral beta2-receptor antagonism.
    • The long-acting formulation of propranolol has an efficacy similar to 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 antagonists. Metoprolol, a relatively selective beta1 antagonist, may be useful in patients with asthma or other pulmonary conditions.
  • Primidone
    • O'Brien initially observed that primidone, when administered to a patient with epilepsy and essential tremor, reduced tremor. In a placebo-controlled study, primidone significantly reduced tremor in otherwise untreated patients and patients treated with propranolol. Doses greater than 250 mg/d did not provide additional benefit.
    • The mechanism of action is unknown. Active metabolites are phenylethylmalonamide (PEMA) and phenobarbital. PEMA has no effect on tremor, and phenobarbital has only modest effect on tremor.
    • Tremor reduction is not correlated with serum levels of primidone or phenobarbital.
    • Adverse effects, if any, usually occur early in the course of treatment, possibly with the first dose. Acute adverse effects are minimized by starting at a very low dose and then slowly increasing the dose. However, some patients are unable to tolerate primidone even at very low doses.
  • Topiramate
    • Topiramate is an anticonvulsant medication that enhances gamma-aminobutyric acid activity, carbonic anhydrase inhibition, antagonism of alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid/kainite receptors, and blockage of voltage-dependent calcium and sodium channels.
    • Multiple studies indicate that tremor is reduced by an average of approximately 20% when compared to placebo.
    • Clinical trials indicate a fairly substantial dropout rate of 40% because of adverse effects such as cognitive difficulty or somnolence.
  • Many other medications have been reported to be of benefit in the treatment of essential tremor. Most of these have been case reports or small open-label studies. 
    • Clozapine
      • A single dose of 12.5 mg of clozapine and placebo were compared in a randomized, double-blind crossover study in patients with drug-resistant essential tremor. Tremor was reduced significantly by clozapine in 13 of 15 patients (P <0.01).
      • A significant reduction of tremor was reported with long-term (open-label) clozapine therapy (39.9 mg/d).
      • No tolerance was observed over 15 months.
    • Mirtazapine: In a small, open-label case series, mirtazapine was reported to reduce tremor in patients with essential tremor and Parkinson disease.
    • Gabapentin: A double-blind crossover trial comparing gabapentin (400 mg tid) to propranolol (40 mg tid) found that both drugs demonstrated significant and comparable reductions in tremor compared to baseline. However, a double-blind, placebo-controlled crossover study identified no difference between gabapentin and placebo.
    • Benzodiazepines: Benzodiazepines, particularly clonazepam and alprazolam, are used commonly in the treatment of essential tremor, but their effectiveness is limited. They probably work to reduce the anxiety that can amplify tremor amplitude.
    • Botulinum toxin: Botulinum toxin has been evaluated for the treatment of essential tremor. Its use in the treatment of tremor of the upper extremities is limited because it commonly causes weakness. It is more useful in the treatment of head tremor because it often provides benefit without unwanted troublesome weakness.
  • Practical management of pharmacologic therapy
    • For patients who require daily maintenance treatment for essential tremor, a decision is made whether to start with primidone or propranolol. Usually, propranolol is started first in younger individuals and primidone is started first in older individuals. Generally, propranolol carries more risk of serious adverse effects in older patients than in younger patients. Additionally, younger patients, particularly those who are in school or working, find the sedating and cognitive side effects of primidone more troublesome than older patients do.
    • If the patient has a relative contraindication to propranolol, such as pulmonary disease or heart block, starting with primidone is preferable; a beta1 antagonist can be tried if necessary.
    • If the patient receives no benefit from the first medication, it is weaned and discontinued before starting the other. If the benefit is partial but insufficient, the initial medication is maintained and the other medication is added.
    • Once an effective maintenance dose of propranolol is achieved, switching to the long-acting preparation is considered. An alternative is to use the long-acting formulation from the beginning, but this requires multiple prescriptions and is more cumbersome.
    • If sufficient benefit is not achieved with primidone or propranolol, other medications are considered based on the severity of the residual tremor.
    • If the tremor is mild and more of a nuisance than disabling, a benzodiazepine is considered, usually clonazepam.
    • For patients with head tremor, cervical injections of botulinum toxin may be given.

Surgical Care

For patients with medically refractory disabling upper extremity tremor, surgery is considered. Stereotactic thalamotomy and thalamic ventralis intermedius nucleus deep brain stimulation (DBS) are the procedures of choice.

Both procedures offer high rates of tremor reduction in the contralateral arm. Recent information suggests that they are also useful in reducing head and voice tremor. Bilateral thalamotomy is associated with a relatively high risk of dysarthria, occurring in as many as 29% of patients, and a risk of cerebral hemorrhage. The potential advantage of thalamic stimulation is that it is adjustable. If the stimulation causes an adverse effect, the rate of stimulation can be modified or discontinued.

In 1996, Benabid et al initially proposed that thalamic stimulation might be a useful procedure on the opposite side in patients who already had a unilateral thalamotomy in an effort to avoid the potentially serious complications of bilateral thalamotomy.31 Thalamic stimulation now is considered the procedure of choice.

  • Thalamotomy
    • In 1997, a retrospective study by Jankovic et al evaluated 60 patients who underwent thalamotomy for medically intractable tremor. Forty-two had Parkinson disease, 6 had essential tremor, 6 had cerebellar tremor, and 6 had posttraumatic tremor. Patients were observed for a mean of 53.4 months and for as long as 13 years. Cessation or moderate-to-marked improvement in contralateral tremor with improvement in function occurred in 86% of patients with Parkinson disease, 83% of patients with essential tremor, 67% of patients with cerebellar tremor, and 50% of patients with posttraumatic tremor. Fourteen of the 60 patients had a total of 18 persistent complications, including weakness in 9, dysarthria in 6, contralateral ataxia in 1, blepharospasm in 1, and pulmonary embolus resulting in death in 1.
    • A study of thalamotomy in 8 patients with essential tremor by Goldman demonstrated a reduction in tremor from moderate-to-severe to mild or no tremor in all 8 patients. Mild persistent dysarthria was seen in 2, and a "mild verbal cognitive defect" was seen in 1.32
    • Stereotactic thalamotomy is less expensive than deep brain stimulation, no hardware remains, and it has been demonstrated to provide long-term efficacy. Potential adverse effects include intracerebral hemorrhage, motor weakness, dystonia, speech disturbance, and memory loss.
  • Thalamic deep brain stimulation
    • In a multicenter study, high-frequency unilateral thalamic stimulation was assessed in 29 patients with essential tremor and 24 with Parkinson disease. A blinded evaluation at 3 months with patients randomized to stimulation on or stimulation off demonstrated a significant reduction in both essential tremor and Parkinson disease contralateral tremor with stimulation on. Measures of function were improved significantly in patients with essential tremor. Stimulation was associated commonly with transient paresthesias. Other adverse events were mild and well tolerated.
    • In 1998, Ondo et al reported an average 83% reduction in contralateral arm tremor in a study of 14 patients with essential tremor.22
    • In 1999, Pahwa et al reported good results with bilateral thalamic deep brain stimulation in 9 patients with essential tremor. Patients experienced 68% improvement in hand tremor following the first surgery and 75% improvement in the opposite hand following the second surgery. Complications were noted in 5 patients and included asymptomatic intracranial hematoma (1), postoperative seizures (1), hematoma over the implanted pulse generator (1), lead repositioning (1), and IPG malfunction (1). Adverse effects related to stimulation were mild and resolved with adjustment of stimulation parameters.33
  • Thalamotomy versus thalamic deep brain stimulation
    • In 1998, a retrospective comparison study by Tasker of deep brain stimulation and thalamotomy in essential tremor and Parkinson disease demonstrated complete contralateral tremor abolition in 42% of patients treated with either procedure, near abolition in 69% of the thalamotomy group and 79% of the deep brain stimulation group, and recurrence in 15% of the deep brain stimulation group and 5% of the thalamotomy group. None of the deep brain stimulation implants and 15% of the thalamotomies had to be repeated. Side effects, including ataxia, dysarthria, and gait disturbance, were more common with thalamotomy (42%) than deep brain stimulation (26%); side effects were persistent in 31% of people undergoing thalamotomy; and those occurring after deep brain stimulation were almost always controlled by adjusting stimulation parameters. Paresthesias were persistent in 19% of patients undergoing thalamotomy and were avoidable in deep brain stimulation by stimulation modification.34
    • In a 1999 report, Taha et al evaluated thalamic deep brain stimulation contralateral to thalamotomy in 23 patients (6 with Parkinson disease, 15 with essential tremor, and 2 with multiple sclerosis); of 20 patients with bilateral limb tremor, 85% improved to having no tremor or only stress-induced tremor. The main advantage of thalamic deep brain stimulation is that it is adjustable; adverse effects from stimulation can be controlled by reducing stimulation. Disadvantages of deep brain stimulation include expense, foreign body implant, need to optimize parameters, and hardware maintenance including battery replacement after several years.35
    • In a prospective study in 2000, Schuurman et al compared thalamic stimulation and thalamotomy in a prospective randomized study of 68 patients with Parkinson disease, essential tremor, or multiple sclerosis. Functional status improved more in the thalamic stimulation group. Tremor was suppressed completely or almost completely in 30 of 33 patients who underwent thalamic stimulation compared with 27 of 34 patients in the thalamotomy group. One patient in the stimulation group died perioperatively after an intracerebral hemorrhage. These investigators concluded that, although thalamotomy and thalamic stimulation are equally effective for tremor suppression, stimulation results in greater functional improvement and has fewer adverse effects.36
    • In a long-term study of a series of patients who underwent thalamic stimulation, the rates of stimulator reoperations, explants, and device failures were relatively high, suggesting that long-term evaluations may be necessary to assess definitively the relative benefits and complications of these procedures. 
    • Gamma knife thalamotomy was studied in patients who were not eligible for open surgical techniques and had medically refractory tremor. Findings indicated that gamma knife thalamotomy was safe and effective.37

Medication

Beta-adrenergic blockers (principally propranolol) and primidone are the first-line treatment 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 more prominent later in treatment with propranolol. Starting with propranolol is preferable in younger individuals, and primidone is started first in older individuals.

Patients are usually started on one of these medications. The drug is introduced at a low dose that is increased slowly until complete response, tolerance, or usual maximum dose is attained. If some benefit is achieved but is incomplete, the other medication may be introduced and 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 rather than frequency 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. Clozapine, an atypical neuroleptic, has been shown to be effective in a randomized, double-blind crossover study of patients who had definite or probable essential tremor and poor response to propranolol or primidone. Thirteen of 15 patients demonstrated greater than 50% improvement of upper extremity tremor with 12.5 mg of clozapine.

Beta-adrenergic blockers

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, Betachron ER)

One of 2 medications of choice for essential tremor, shown to be effective in double-blind, placebo-controlled trials. Nonselective beta-adrenergic blocker with negative inotropic, chronotropic, and dromotropic properties. Lipophilic with CNS effects. Mechanism of action probably related to peripheral beta2 antagonism. Long-acting formulation has efficacy similar to that of standard formulation and may allow fewer daily doses.
In general, beta1 antagonists are more effective than placebo but are not as effective as beta2 antagonists. Metoprolol, a relatively selective beta1 antagonist, may be useful in patients with asthma and other pulmonary conditions.

Adult

20 mg PO qam initially; increase by 20 mg/d qwk to 20 mg tid; continue increase by 20 mg/d qwk until tremor is adequately controlled, adverse effects become intolerable, or usual maximum of 240-320 mg/d is reached
Effective dose range is 40-320 mg/d in divided doses; typical dose range is 120 mg (40 mg tid) to 240 mg/d

Pediatric

Not established; dosing for other indications ranges from 1-4 mg/kg/d in divided doses

Catecholamine-depleting drugs may produce excessive reduction in resting sympathetic nervous activity, resulting in hypotension, marked bradycardia, vertigo, syncopal attack, or orthostatic hypotension; calcium channel blockers, particularly verapamil, may decrease cardiac contractility or AV conduction; anti-arrhythmic drugs may increase cardiac effects; phenothiazines may have additive hypotensive activity; chlorpromazine may reduce clearance; high doses may potentiate effects of neuromuscular blocking agents; cimetidine can reduce clearance

Documented hypersensitivity; sinus bradycardia; second- or third-degree heart block; congestive heart failure; cardiogenic shock; allergic bronchospastic disease; Raynaud disease; malignant hypertension

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in diabetes mellitus, myasthenia, nonallergic bronchospastic disease, and impaired hepatic or renal function; potential adverse effects include bradycardia, hypotension, heart failure, fatigue, depression, weight gain, male impotence, nausea, diarrhea, and rash; lethargy, fatigue, and depression may emerge over time; relative contraindications include heart failure, second- or third-degree AV block, asthma, chronic obstructive pulmonary disease, and insulin-dependent diabetes mellitus; may mask symptoms of thyrotoxicosis or hypoglycemia or interfere with glaucoma screening tests; abrupt withdrawal may precipitate unstable angina or myocardial infarction in patients with angina or coronary artery disease

Anticonvulsant agents

Both primidone and, to a lesser extent, phenobarbital have demonstrated tremor-suppressing effects. Mechanism of action is unknown, but it presumably involves the CNS.


Primidone (Mysoline)

Metabolized to phenobarbital and PEMA. 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 independent mechanism for its effect on tremor.
Strongly recommended that treatment be initiated with low doses because adverse effects at initiation of treatment are common. Start with one quarter or one half of 50-mg tablet at bedtime and increase dose slowly every week. Alternatively, introduce primidone using 250 mg/5 mL suspension. Start with 1 drop at bedtime and increase dose by 1 drop each night for 20 nights. Then convert to 50-mg tab and increase slowly every week.
For patients who initially respond but develop tolerance later, increasing dose to as high as 1000 mg/d in effort to regain benefit is advisable.

Adult

25 mg/d (half of 50-mg tab) PO qhs, then increase by 25 mg/d qwk to dose of 100 mg/d
When further increase is required, split dose one third in morning and two thirds at bedtime, up to usual maximum daily dose of 300 mg/d
Usual dose range is 12.5-250 mg/d PO

Pediatric

Not established

Alcohol, phenobarbital, heparin, isoniazid, and phenytoin increase blood levels; phenobarbital, a metabolite of primidone, is both competitive inhibitor and inducer of hepatic enzymes; enhances hepatic clearance of oral contraceptives, steroids, calcium channel blockers, theophylline, digitoxin, acetaminophen, cimetidine, cyclosporin, lamotrigine, felbamate, topiramate, and tiagabine; has variable interactions with phenytoin

Documented hypersensitivity; porphyria

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Potential adverse effects include sedation, ataxia, vertigo, dizziness, nausea, vomiting, diplopia, and nystagmus; these effects usually occur, if at all, early in course of treatment and may occur with first dose; other adverse effects include maculopapular and morbilliform rash, leukopenia, thrombocytopenia, SLE, and lymphadenopathy; ataxia and vertigo very common and tend to resolve with repeated use; overdose produces symptoms similar to barbiturate overdose, including profound CNS depression, shock, and respiratory depression; caution in patients with renal or hepatic impairment; abrupt discontinuation of medication may precipitate status epilepticus; caution in pulmonary insufficiency; may have paradoxical effects in children, including irritability, hyperactivity, and disturbed sleep


Topiramate (Topamax)

Mechanism of action unknown but blockage of voltage-dependent sodium channels and augmentation of GABA thought to play a role. Not extensively metabolized and excreted unchanged in the urine.

Adult

25 mg/d PO and increase 25 mg/wk in divided doses to maximum dose of 400 mg/d (200 mg bid)

Pediatric

Not established

Phenytoin, carbamazepine, and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use topiramate with extreme caution when administering concurrently with CNS depressants because may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Risk of developing a kidney stone is increased 2-4 times over that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients taking topiramate should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop can lead to glaucoma; primary treatment is discontinuation of topiramate; if left untreated, serious sequelae, including permanent vision loss, may occur; oligohidrosis and hyperthermia has been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior and during activity and warm temperatures)
May cause hyperchloremic nonanion gap metabolic acidosis, acute or chronic metabolic acidosis resulting in hyperventilation, and nonspecific symptoms, such as fatigue and anorexia; more severe adverse effects include cardiac arrhythmias or stupor; chronic untreated metabolic acidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate

Atypical neuroleptics

In a randomized, double-blind crossover study of 15 patients who had definite or probable essential tremor and poor response to propranolol or primidone, 13 showed greater than 50% improvement of upper extremity tremor with 12.5 mg of clozapine.


Clozapine (Clozaril)

Mechanism of effect in essential tremor unknown. Long-term effects in essential tremor have not been studied. May be tried before resorting to surgery when other methods have failed. Weakly antidopaminergic, antiadrenergic (alpha1 and alpha2 receptors), anticholinergic, antihistaminergic (H1, H3), and antiserotonergic (5-HT1c, 5-HT2, 5-HT3).

Adult

Start at dose of 12.5 mg/d PO or less; introduce using a chip (~1/8) of a 25-mg tab and increase slowly
Usual dose 12.5-50 mg/d

Pediatric

Not established

Should not be used with drugs known to cause agranulocytosis or otherwise suppress bone marrow function; increases anticholinergic effect of anticholinergics; because of CNS depressive effects, should not be used with alcohol; respiratory and cardiac functions should be monitored when used with other psychotropic drugs, particularly benzodiazepines; because protein bound, may cause elevations in plasma concentrations of other protein-bound drugs, such as warfarin or digitoxin; cimetidine, erythromycin, and SSRIs may increase plasma levels; phenytoin or carbamazepine may decrease plasma levels; drugs that are metabolized by cytochrome P450 2D6 may affect levels of either clozapine or other drug

Documented hypersensitivity; myeloproliferative disorders; uncontrolled epilepsy; severe CNS depression or comatose state; history of agranulocytosis or severe granulocytopenia induced by clozapine

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Frequent blood monitoring required because of risk of agranulocytosis, recommended baseline WBC count and differential prior to treatment and WBC count qwk for 6 mo; if WBC maintained at >3000/mm3 and ANC maintained at >1500/mm3, then testing may be carried out on alternate wk until 4 wk after drug discontinued
Other potential adverse effects include seizures, sedation, dizziness/vertigo, delirium, hypotension, tachycardia, weight gain, sialorrhea, elevated liver enzymes, constipation, nausea, enuresis, fever, and neuromuscular effects; sedation commonly resolves after several wk

Antidepressant agents

In a recent case series report, 4 patients (3 with Parkinson disease and 1 with essential tremor) who had responded initially to propranolol had improvement of tremor with mirtazapine.


Mirtazapine (Remeron)

Potent 5-HT2, 5-HT3, and H1 antagonist; moderate peripheral alpha1-adrenergic antagonist and moderate antagonist of muscarinic receptors. Half-life is 20-40 h.

Adult

15 mg/d PO qam initially (limited data available); increase to 15 mg PO bid if necessary
Usual dose 15-45 mg/d

Pediatric

Not established

If used with MAOIs may have serious and sometimes fatal interactions

Documented hypersensitivity; MAOI use within last 14 d; caution in patients with mania or hypomania

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with bipolar disorder or hypomania, may precipitate mania; potential adverse effects include somnolence, dizziness, increased appetite, and increased transaminases; rare cases of symptomatic agranulocytosis (2 of 2796) and 1 case of severe neutropenia reported—all recovered with discontinuation of medication; can cause orthostatic hypotension; use with care in patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension or in patients predisposed to hypotension; discontinue drug in patients with signs or symptoms of neutropenia or agranulocytosis; clearance decreased in liver or kidney disease and in elderly people, particularly elderly men (as much as 40%)

More on Essential Tremor

Overview: Essential Tremor
Differential Diagnoses & Workup: Essential Tremor
Treatment & Medication: Essential Tremor
Follow-up: Essential Tremor
References
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References

  1. Louis ED, Vonsattel JP. The emerging neuropathology of essential tremor. Mov Disord. Jan 30 2008;23(2):174-82. [Medline].

  2. Shill HA, Adler CH, Sabbagh MN, et al. Pathologic findings in prospectively ascertained essential tremor subjects. Neurology. Apr 15 2008;70(16 Pt 2):1452-5. [Medline].

  3. Louis ED, Zheng W, Mao X, Shungu DC. Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study. Neurology. Aug 7 2007;69(6):515-20. [Medline].

  4. Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB. Essential tremor associated with focal nonnigral Lewy bodies: a clinicopathologic study. Arch Neurol. Jun 2005;62(6):1004-7. [Medline].

  5. Louis ED, Vonsattel JP, Honig LS, Ross GW, Lyons KE, Pahwa R. Neuropathologic findings in essential tremor. Neurology. Jun 13 2006;66(11):1756-9. [Medline].

  6. Shin DH, Han BS, Kim HS, Lee PH. Diffusion tensor imaging in patients with essential tremor. AJNR Am J Neuroradiol. Jan 2008;29(1):151-3. [Medline].

  7. Bermejo-Pareja F, Louis ED, Benito-Leon J. Risk of incident dementia in essential tremor: a population-based study. Mov Disord. Aug 15 2007;22(11):1573-80. [Medline].

  8. Benito-Leon J, Louis ED, Bermejo-Pareja F. Elderly-onset essential tremor is associated with dementia. Neurology. May 23 2006;66(10):1500-5. [Medline].

  9. Klebe S, Stolze H, Grensing K, Volkmann J, Wenzelburger R, Deuschl G. Influence of alcohol on gait in patients with essential tremor. Neurology. Jul 12 2005;65(1):96-101. [Medline].

  10. Daniels C, Peller M, Wolff S, et al. Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor. Neurology. Oct 24 2006;67(8):1452-6. [Medline].

  11. Ross GW, Dickson D, Cersosimo M. Pathological investigation of essential tremor. Neurology. Apr 2004;62(7) S5:A537-A538.

  12. Dogu O, Sevim S, Camdeviren H, et al. Prevalence of essential tremor: door-to-door neurologic exams in Mersin Province, Turkey. Neurology. Dec 23 2003;61(12):1804-6. [Medline].

  13. Louis ED, Benito-Leon J, Ottman R, Bermejo-Pareja F. A population-based study of mortality in essential tremor. Neurology. Nov 20 2007;69(21):1982-9. [Medline].

  14. Louis ED, Barnes LF, Ford B, Pullman SL, Yu Q. Ethnic differences in essential tremor. Arch Neurol. May 2000;57(5):723-7. [Medline].

  15. Tan EK, Lum SY, Prakash KM. Clinical features of childhood onset essential tremor. Eur J Neurol. Dec 2006;13(12):1302-5. [Medline].

  16. Louis ED, Dogu O. Does age of onset in essential tremor have a bimodal distribution? Data from a tertiary referral setting and a population-based study. Neuroepidemiology. 2007;29(3-4):208-12. [Medline].

  17. Louis ED, Ottman R. Study of possible factors associated with age of onset in essential tremor. Mov Disord. Nov 2006;21(11):1980-6. [Medline].

  18. [Best Evidence] Thawani SP, Schupf N, Louis ED. Essential tremor is associated with dementia: prospective population-based study in New York. Neurology. Aug 25 2009;73(8):621-5. [Medline].

  19. Chatterjee A, Jurewicz EC, Applegate LM, Louis ED. Personality in essential tremor: further evidence of non-motor manifestations of the disease. J Neurol Neurosurg Psychiatry. Jul 2004;75(7):958-61. [Medline].

  20. Miller KM, Okun MS, Fernandez HF, Jacobson CE 4th, Rodriguez RL, Bowers D. Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor. Mov Disord. Apr 15 2007;22(5):666-72. [Medline].

  21. Benito-Leon J, Louis ED, Bermejo-Pareja F. Reported hearing impairment in essential tremor: a population-based case-control study. Neuroepidemiology. 2007;29(3-4):213-7. [Medline].

  22. Ondo W, Jankovic J, Schwartz K, Almaguer M, Simpson RK. Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor. Neurology. Oct 1998;51(4):1063-9. [Medline].

  23. Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. Nov 2001;124:2278-86. [Medline].

  24. Ma S, Davis TL, Blair MA, et al. Familial essential tremor with apparent autosomal dominant inheritance: should we also consider other inheritance modes?. Mov Disord. Sep 2006;21(9):1368-74. [Medline].

  25. Deng H, Le W, Jankovic J. Genetics of essential tremor. Brain. Jun 2007;130:1456-64. [Medline].

  26. Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain. Sep 2006;129:2318-31. [Medline].

  27. Higgins JJ, Lombardi RQ, Pucilowska J, Jankovic J, Tan EK, Rooney JP. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology. Feb 8 2005;64(3):417-21. [Medline].

  28. Walter AR, Bower JH, Ahlskog JE et al. Increased risk of essential tremor in first-degree relative of patients with Parkinson's disease. Mov Disord. Aug 15 2007;22(11).

  29. Doep F. Plotkin M, Siegel L. Brain parenchyma sonography and 123I-FP-CIT SPECT in Parkinson's disease and essential tremor. Mov. Disord. Dec 7 1007;23(3):(405-410).

  30. Stockner H, Sojer M, K KS, et al. Midbrain sonography in patients with essential tremor. Mov Disord. Feb 15 2007;22(3):414-7. [Medline].

  31. Benabid AL, Pollak P, Gao D, et al. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg. Feb 1996;84(2):203-14. [Medline].

  32. Goldman MS, Ahlskog JE, Kelly PJ. The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor. J Neurosurg. Jun 1992;76(6):924-8. [Medline].

  33. Pahwa R, Lyons KL, Wilkinson SB, et al. Bilateral thalamic stimulation for the treatment of essential tremor. Neurology. Oct 22 1999;53(7):1447-50. [Medline].

  34. Tasker RR. Deep brain stimulation is preferable to thalamotomy for tremor suppression. Surg Neurol. Feb 1998;49(2):145-53; discussion 153-4. [Medline].

  35. Taha JM, Janszen MA, Favre J. Thalamic deep brain stimulation for the treatment of head, voice, and bilateral limb tremor. J Neurosurg. Jul 1999;91(1):68-72. [Medline].

  36. Schuurman PR, Bosch DA, Bossuyt PM, et al. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. Feb 17 2000;342(7):461-8. [Medline].

  37. Kondziolka D, Ong JG, Lee JY, Moore RY, Flickinger JC, Lunsford LD. Gamma Knife thalamotomy for essential tremor. J Neurosurg. Jan 2008;108(1):111-7. [Medline].

  38. Agundez JA, Jimenez-Jimenez FJ, Tejeda R, et al. CYP2D6 polymorphism is not associated with essential tremor. Eur Neurol. 1997;38(2):99-104. [Medline].

  39. Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential tremor. Brain. Aug 1994;117 (Pt 4):805-24. [Medline].

  40. Boecker H, Wills AJ, Ceballos-Baumann A, et al. The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study. Ann Neurol. May 1996;39(5):650-8. [Medline].

  41. Brin MF, Koller W. Epidemiology and genetics of essential tremor. Mov Disord. 1998;13 Suppl 3:55-63. [Medline].

  42. Bucher SF, Seelos KC, Dodel RC, Reiser M, Oertel WH. Activation mapping in essential tremor with functional magnetic resonance imaging. Ann Neurol. Jan 1997;41(1):32-40. [Medline].

  43. Busenbark K, Barnes P, Lyons K, Ince D, Villagra F, Koller WC. Accuracy of reported family histories of essential tremor. Neurology. Jul 1996;47(1):264-5. [Medline].

  44. Chouinard S, Louis ED, Fahn S. Agreement among movement disorder specialists on the clinical diagnosis of essential tremor. Mov Disord. Nov 1997;12(6):973-6. [Medline].

  45. Cleeves L, Findley LJ. Beta-adrenoreceptor mechanisms in essential tremor: a comparative single dose study of the effect of a non-selective and a beta-2 selective adrenoreceptor antagonist. J Neurol Neurosurg Psychiatry. Sep 1984;47(9):976-82. [Medline].

  46. Critchley M. Observations on Essential (Heredofamilial) Tremor. Brain. 1949;72:113-139.

  47. Deeb J. Gannon K. Shah M, et al. Comparison of datscan imaging and smell testing in essential tremor and Parkinson disease. Jr Neurol, Neurosurg. & Psych. Sept 2007;78(9):1018-1019.

  48. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. [Medline].

  49. Elble RJ, Dubinsky RM, Ala T. Alzheimer's disease and essential tremor finally meet. Mov Disord. Aug 15 2007;22(11):1525-7. [Medline].

  50. Factor SA, Friedman JH. The emerging role of clozapine in the treatment of movement disorders. Mov Disord. Jul 1997;12(4):483-96. [Medline].

  51. Findley LJ. Expanding clinical dimensions of essential tremor. J Neurol Neurosurg Psychiatry. Jul 2004;75(7):948-9. [Medline].

  52. Findley LJ, Shah M. Muhammed N, et al. Olfactory tests distinguish essential from parkinsonian tremor. Evidence of enhanced detection and age resistance in familial essential tremor. J Neurol Neurosurg Psych. Jan 2006;77(1):140.

  53. Gironell A, Kulisevsky J, Barbanoj M, Lopez-Villegas D, Hernandez G, Pascual-Sedano B. A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor. Arch Neurol. Apr 1999;56(4):475-80. [Medline].

  54. Gorman WP, Cooper R, Pocock P, Campbell MJ. A comparison of primidone, propranolol, and placebo in essential tremor, using quantitative analysis. J Neurol Neurosurg Psychiatry. Jan 1986;49(1):64-8. [Medline].

  55. Gulcher JR, Jonsson P, Kong A, et al. Mapping of a familial essential tremor gene, FET1, to chromosome 3q13. Nat Genet. Sep 1997;17(1):84-7. [Medline].

  56. Hallett M. Overview of human tremor physiology. Mov Disord. 1998;13 Suppl 3:43-8. [Medline].

  57. Higgins JJ, Loveless JM, Jankovic J, Patel PI. Evidence that a gene for essential tremor maps to chromosome 2p in four families. Mov Disord. Nov 1998;13(6):972-7. [Medline].

  58. Higgins JJ, Pho LT, Nee LE. A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov Disord. Nov 1997;12(6):859-64. [Medline].

  59. Hua SE, Lenz FA, Zirh TA, Reich SG, Dougherty PM. Thalamic neuronal activity correlated with essential tremor. J Neurol Neurosurg Psychiatry. Feb 1998;64(2):273-6. [Medline].

  60. Hubble JP, Busenbark KL, Pahwa R, Lyons K, Koller WC. Clinical expression of essential tremor: effects of gender and age. Mov Disord. Nov 1997;12(6):969-72. [Medline].

  61. Hulihan J, Connor GS, Shu-Chen W, et al. Topiramate in essential tremor: pooled data from a double-blind, placebo-controlled, crossover trial. American Academy of Neurology 2003 Abstracts: P04.068. Class II. Neurology. 2003.

  62. Jankovic J, Beach J, Pandolfo M, Patel PI. Familial essential tremor in 4 kindreds. Prospects for genetic mapping. Arch Neurol. Mar 1997;54(3):289-94. [Medline].

  63. Jankovic J, Schwartz K, Clemence W, Aswad A, Mordaunt J. A randomized, double-blind, placebo-controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord. May 1996;11(3):250-6. [Medline].

  64. Koller W, Pahwa R, Busenbark K, et al. High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor. Ann Neurol. Sep 1997;42(3):292-9. [Medline].

  65. Koller WC. Dose-response relationship of propranolol in the treatment of essential tremor. Arch Neurol. Jan 1986;43(1):42-3. [Medline].

  66. Koller WC. Long-acting propranolol in essential tremor. Neurology. Jan 1985;35(1):108-10. [Medline].

  67. Koller WC, Royse VL. Efficacy of primidone in essential tremor. Neurology. Jan 1986;36(1):121-4. [Medline].

  68. Koller WC, Royse VL. Time course of a single oral dose of propranolol in essential tremor. Neurology. Oct 1985;35(10):1494-8. [Medline].

  69. Koller WC, Vetere-Overfield B. Acute and chronic effects of propranolol and primidone in essential tremor. Neurology. Dec 1989;39(12):1587-8. [Medline].

  70. Lorenz D, Frederiksen H, Moises H, Kopper F, Deuschl G, Christensen K. High concordance for essential tremor in monozygotic twins of old age. Neurology. Jan 27 2004;62(2):208-11. [Medline].

  71. Louis ED, Ford B, Bismuth B. Reliability between two observers using a protocol for diagnosing essential tremor. Mov Disord. Mar 1998;13(2):287-93. [Medline].

  72. Louis ED, Ford B, Lee H, Andrews H, Cameron G. Diagnostic criteria for essential tremor: a population perspective. Arch Neurol. Jun 1998;55(6):823-8. [Medline].

  73. Louis ED, Ford B, Pullman SL. Prevalence of asymptomatic tremor in relatives of patients with essential tremor. Arch Neurol. Feb 1997;54(2):197-200. [Medline].

  74. Louis ED, Ottman R. How familial is familial tremor? The genetic epidemiology of essential tremor. Neurology. May 1996;46(5):1200-5. [Medline].

  75. Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? estimates of the prevalence of essential tremor throughout the world. Mov Disord. Jan 1998;13(1):5-10. [Medline].

  76. Louis ED, Shungu DC, Chan S, Mao X, Jurewicz EC, Watner D. Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imaging study. Neurosci Lett. Nov 15 2002;333(1):17-20. [Medline].

  77. Louis ED, Vonsattel JP, Honig LS, et al. Essential tremor associated with pathologic changes in the cerebellum. Arch Neurol. Aug 2006;63(8):1189-93. [Medline].

  78. Louis ED, Wendt KJ, Pullman SL, Ford B. Is essential tremor symmetric? Observational data from a community-based study of essential tremor. Arch Neurol. Dec 1998;55(12):1553-9. [Medline].

  79. Louis ED, Zheng W, Jurewicz EC, et al. Elevation of blood beta-carboline alkaloids in essential tremor. Neurology. Dec 24 2002;59(12):1940-4. [Medline].

  80. Ogawa N, Takayama H, Yamamoto M. Comparative studies on the effects of beta-adrenergic blockers in essential tremor. J Neurol. Oct 1987;235(1):31-3. [Medline].

  81. Ondo WG, Hunter C, Moore W. A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson's disease. Neurology. Jan 13 2004;62(1):37-40. [Medline].

  82. Ondo WG, Sutton L, Dat Vuong K, Lai D, Jankovic J. Hearing impairment in essential tremor. Neurology. Oct 28 2003;61(8):1093-7. [Medline].

  83. Pact V, Giduz T. Mirtazapine treats resting tremor, essential tremor, and levodopa-induced dyskinesias. Neurology. Sep 22 1999;53(5):1154. [Medline].

  84. Rajput A, Robinson CA, Rajput AH. Essential tremor course and disability: A clinicopathologic study of 20 cases. Neurology. Mar 23 2004;62(6):932-6. [Medline].

  85. Schrag A, Muenchau A, Bhatia KP, Quinn NP, Marsden CD. Overdiagnosis of essential tremor. Lancet. May 1 1999;353(9163):1498-9. [Medline].

  86. Wasielewski PG, Burns JM, Koller WC. Pharmacologic treatment of tremor. Mov Disord. 1998;13 Suppl 3:90-100. [Medline].

  87. Zirh A, Reich SG, Dougherty PM, Lenz FA. Stereotactic thalamotomy in the treatment of essential tremor of the upper extremity: reassessment including a blinded measure of outcome. J Neurol Neurosurg Psychiatry. Jun 1999;66(6):772-5. [Medline].

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Further Reading

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Keywords

essential tremor, essential tremor treatment, movement disorder, benign essential tremor, familial tremor, senile tremor

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Contributor Information and Disclosures

Author

Deborah A Burke, MD, Consulting Staff, Sub-investigator, Clinician, Movement Disorder/Parkinson's Disease Center, University of South Florida; Investigator, Physician, Roskamp Institute Memory Clinic
Deborah A Burke, MD is a member of the following medical societies: American Academy of Neurology and Movement Disorders Society
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Hauser, MD, MBA, Professor of Neurology, Molecular Pharmacology and Physiology, Director, Parkinson's Disease and Movement Disorders Center, University of South Florida; Clinical Chair, Signature Interdisciplinary Program in Neuroscience
Robert A Hauser, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Neuroimaging, and Movement Disorders Society
Disclosure: Allergan Sales, LLC Honoraria Speaking and teaching; Boehringer Ingelheim  Honoraria Consulting; Genzyme Corporation Honoraria Consulting; GlaxoSmithKline Honoraria Consulting; IMPAX Laboratories, Inc. Honoraria Consulting; Novartis Pharmaceuticals Corp. Honoraria Consulting; Schering Plough  Consulting; Solvay Pharmeceuticals Honoraria Consulting; Teva Neuroscience Honoraria Speaking and teaching

Theresa McClain, MSN, ARNP, Parkinson's Disease and Movement Disorders Center, University of South Florida
Theresa McClain, MSN, ARNP is a member of the following medical societies: Sigma Theta Tau International
Disclosure: Teva Consulting fee Consulting; GSK Consulting fee Consulting; Valeant Pharm Consulting fee Consulting; Solvay Consulting fee Consulting; Shering Plough Consulting fee Consulting

Medical Editor

Daniel H Jacobs, MD, Associate Professor of Neurology, University of Central Florida College of Medicine
Daniel H Jacobs, MD is a member of the following medical societies: American Academy of Neurology, American Society of Neurorehabilitation, and Society for Neuroscience
Disclosure: Teva Pharmaceutical Grant/research funds Consulting; Biogen Idex Grant/research funds Independent contractor; Serono EMD Royalty Speaking and teaching; Pfizer Royalty Speaking and teaching; Berlex Royalty Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Nestor Galvez-Jimenez, MD, MSc, MHA, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida
Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

 
 
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