Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

no dysfunction or embarrassment

1st line – observation

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ACUTE
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no dysfunction or embarrassment
1st line – 

observation

Pharmacotherapy is not indicated for mild cases that do not cause dysfunction or embarrassment.[6] For these patients, observation is all that is required.

dysfunction or embarrassment

1st line – pharmacotherapy

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ACUTE
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dysfunction or embarrassment
1st line – 

pharmacotherapy

Medical therapy may be used to improve function (e.g., using a smartphone, performing work-related tasks) or reduce embarrassment (e.g., the inability to eat or drink in public without making a mess) associated with the disorder. First-line drugs include propranolol and primidone. Choice of treatment depends on concurrent medical conditions and potential adverse effects.[89]

Propranolol has been shown to reduce limb tremor across studies with various outcome measures.[88]​ The extended-release formulation of propranolol can provide a long duration of tremor suppression. Relative contraindications include bradycardia, asthma, diabetes mellitus, atrioventricular block, and congestive heart failure. Periodic monitoring of heart rate to evaluate for the development of bradycardia is advisable in older patients.

Primidone is an alternative first-line option. An acute toxic reaction of ataxia, nausea, and vomiting is not uncommon when beginning primidone, and these adverse effects cannot be circumvented even with low starting doses or a slow titration schedule.[90]

Several second-line agents can be used to treat ET if primidone and propranolol are either ineffective or not tolerated. These include gabapentin, alprazolam, and topiramate.[97] 

Primary options

propranolol hydrochloride: 40 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 320 mg/day given in 2-3 divided doses; 60 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 320 mg/day

OR

primidone: 12.5 to 25 mg orally once daily at bedtime initially, increase gradually according to response, maximum 750 mg/day given in 1-2 divided doses

Secondary options

gabapentin: 300 mg orally (immediate-release) three times daily initially, increase gradually according to response, maximum 3600 mg/day

OR

alprazolam: 0.25 mg orally (immediate-release) three times daily initially, increase gradually according to response, maximum 3 mg/day

OR

topiramate: 25-50 mg orally (immediate-release) once daily at bedtime initially, increase gradually according to response, maximum 400 mg/day given in 1-2 divided doses

2nd line – deep brain stimulation (DBS)

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ACUTE
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dysfunction or embarrassment
2nd line – 

deep brain stimulation (DBS)

DBS of the nucleus ventralis intermedius (VIM) of the thalamus is a highly successful neurosurgical method for the treatment of pharmacotherapy-refractory essential tremor (ET).[122]

As this is an elective procedure, determining a favorable risk-to-benefit ratio is paramount. This includes accurately diagnosing the patient's tremor, establishing that appropriate medical therapy was not successful, estimating the improvement in the patient's functional capacity and quality of life that would result with tremor control, and assessing the patient's suitability for surgery (i.e., age, cognitive function, and medical comorbidities).

A multidisciplinary team that includes a movement disorders-specialized neurologist, a neurosurgeon, and a neuropsychologist should be involved. For centers where such specialists are not readily available, simpler screens have been designed to help identify potential candidates for DBS.[99][100][101][102][103]

An alternative target for DBS is the caudal zona incerta (cZi), also known as the posterior subthalamic area. A new strategy whereby the DBS lead is implanted through the VIM thalamic nucleus into the cZi has been proposed, which allows stimulation in either or both targets. This new target shows substantial promise as an effective target for suppressing contralateral tremor in these patients, with a long-lasting effect.[123][124][125]

3rd line – focused ultrasound thalamotomy with MRI guidance

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ACUTE
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dysfunction or embarrassment
3rd line – 

focused ultrasound thalamotomy with MRI guidance

Magnetic resonance imaging (MRI)-guided focused ultrasound thalamotomy is an alternative to deep brain stimulation (DBS) surgery.

The American Society for Stereotactic and Functional Neurosurgery (ASSFN) recommends transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) thalamotomy as a treatment option for patients with refractory essential tremor (ET), who have an appendicular tremor that interferes with quality of life, and that are expected to have a significant improvement with unilateral treatment.[131]

In the UK, TcMRgFUS thalamotomy is a treatment option for refractory ET in patients not eligible for DBS where special arrangements for clinical governance, consent, and audit or research are in place.[134][135]

Similar to DBS, the relative risk and benefits should be considered. The long-term effects and side effects are unclear.[126][134]

4th line – gamma knife thalamotomy

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ACUTE
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dysfunction or embarrassment
4th line – 

gamma knife thalamotomy

Another surgical option for refractory essential tremor is gamma knife thalamotomy, which is especially suitable for older patients or those with high surgical risk for deep brain stimulation or radiofrequency thalamotomy.[132]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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