Essential Tremor

Essential Tremor (ET) is a common cause of action tremor. Mild cases may not require treatment, while intermittent symptoms may be managed with drugs like propranolol or primidone. Severe and drug-resistant cases may benefit from surgical options like deep brain stimulation or thalamotomy.

Essential Tremor Overview:

Essential tremor (ET) is the most common cause of action tremor in adults. It involves the hands and is worsen by movement. For treatment of ET, it is advisable to exclude other secondary causes of tremor. Individuals with mild ET or no tremor- related disability usually do not require additional treatment. Also, intermittent drug treatment is considered for those whose ET worsens by stressful social occasions. For patients with continuous symptoms that cause disability, medical treatment has to be considered with either beta blocker or primidone. (1, 2, 3, 4)

Propranolol and Other Beta Blockers for ET:

Propranolol (60 mg daily which could be titrated gradually up to a maximum of 240 mg daily), as a beta blocker is the most effective medication for ET. Also, selective beta- 1 blockers, such as atenolol (25mg daily), nadolol (40mg per day) may be used instead of propranolol in patients with bronchospasm or asthma. (5, 6)

Primidone for ET Treatment:

Primidone is also effective for the treatment of ET and can be alternative to beta blockers. It is started at a dose of 25 mg daily and the dose can be titrated gradually up to a maximum of 250mg/ day. (7)

Combined and Alternative Drug Therapies:

If ET is resistant to monotherapy with either beta blacker or primidone, then, the two drugs can be used together. If both drugs are ineffective to control ET, then other medical drugs could be tried including, gabapentin, nimodipine or topiramate. Gabapentin monotherapy at a dose of 300 mg three times daily may be effective to control ET. Nimodipine (30 mg four times daily) is a calcium channel blocker, and is possibly effective for the treatment of ET. (8, 9)

Topiramate and its Effects:

Topiramate (25 mg once or twice daily) may reduce limb tremor associated with ET and improve functional disability, but it is associated with a high rate of toxicities including not only paraesthesia, but also, weight loss, somnolence, attention difficulty, memory loss. The initial dose of topiramate is 25 mg once daily, followed by weekly increases of 25 to 50 mg per day up to a maximum of 400 mg per day as per tolerance and side effects. (1)

Adjunctive Drug Therapies:

Adjunctive drugs include benzodiazepines, such as, alprazolam 0.125-0.25mg daily as an anxiolytic may partially reduce ET. (10)

Botulinum Toxin for ET:

Botulinum toxin type-A injections may provide modest benefit in ET, but have been associated with dose- dependent hand weakness. (11, 12)

Surgical Therapy for ET:

Surgical therapy include, deep brain stimulation (DBS) of bilateral ventral intermediate nuclei of the thalamus, magnetic resonance imaging (MRI)-guided focused ultrasound, and stereotactic thalamotomy appear to be effective for severely disabling ET which is medication resistant. (13, 14)

References

1-Rajput AH, Rajput A. Medical treatment of essential tremor. J Cent Nerv Syst Dis 2014; 6:29.

2-Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord 2018; 33:75.

3-Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol 2011; 10:148.

4-Dietrichson P, Espen E. Primidone and propranolol in essential tremor: a study based on quantitative tremor recording and plasma anticonvulsant levels. Acta Neurol Scand 1987; 75:332.

5- 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 1986; 49:64.

6-Leigh PN, Jefferson D, Twomey A, Marsden CD. Beta-adrenoreceptor mechanisms in essential tremor; a double-blind placebo controlled trial of metoprolol, sotalol and atenolol. J Neurol Neurosurg Psychiatry 1983; 46:710.

7-Nida A, Alston J, Schweinfurth J. Primidone Therapy for Essential Vocal Tremor. JAMA Otolaryngol Head Neck Surg 2016; 142:117.

8-Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Neurology 2011; 77:1752.

9-Bruno E, Nicoletti A, Quattrocchi G, et al. Topiramate for essential tremor.Cochrane Database Syst Rev 2017; 4:CD009683.

10-Bruno E, Nicoletti A, Quattrocchi G, et al. Alprazolam for essential tremor. Cochrane Database Syst Rev 2015; :CD009681.

11-Mittal SO, Machado D, Richardson D, et al. Botulinum toxin in essential hand tremor - A randomized double-blind placebo-controlled study with customized injection approach. Parkinsonism Relat Disord 2018; 56:65.

12-Justicz N, Hapner ER, Josephs JS, et al. Comparative effectiveness of propranolol and botulinum for the treatment of essential voice tremor. Laryngoscope 2016; 126:113.

13-Blomstedt P, Sandvik U, Tisch S. Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor. Mov Disord 2010; 25:1350.

14-Louis ED. Treatment of Medically Refractory Essential Tremor. N Engl J Med 2016; 375:792.