What is the treatment for essential tremor?

Treatment of Essential Tremor

Propranolol (80-240 mg/day) or primidone are the first-line treatments for essential tremor, effective in up to 70% of patients, with propranolol being the most established medication having demonstrated efficacy for over 40 years. 1

When to Initiate Treatment

• Treatment should only be started when tremor symptoms interfere with function or quality of life, not simply because tremor is present. 1
• For tremor that is disabling only during periods of stress or anxiety, propranolol or benzodiazepines can be used intermittently during those specific periods. 2

First-Line Pharmacological Options

Propranolol:

• Dosage range: 80-240 mg/day 1, 3
• Most established medication with over 40 years of demonstrated efficacy 4, 1
• Can provide dual benefits in patients with both essential tremor and hypertension 1, 5

Primidone:

• Equally effective first-line option recommended by the American Academy of Neurology 1
• Therapeutic benefit can occur even when derived phenobarbital levels remain subtherapeutic, confirming primidone itself has anti-tremor properties 1
• Clinical benefits may not become apparent for 2-3 months, so an adequate trial period is essential 1
• Women of childbearing age must be counseled about teratogenic risks (neural tube defects) 1
• Behavioral disturbances, irritability, and sleep disturbances can occur, particularly at higher doses 1

Alternative Beta-Blockers

If propranolol causes adverse effects, other beta-blockers may be tried:

• Nadolol: 40-320 mg daily 1
• Metoprolol: 25-100 mg extended release daily or twice daily 4, 1
• Timolol: 20-30 mg/day 1
• Atenolol: Limited evidence for moderate effect 1, 2

Second-Line Medications

If first-line agents fail or are not tolerated:

• Topiramate: Established efficacy as second-line option 6, 7
• Gabapentin: Limited evidence for moderate efficacy 1, 7
• Benzodiazepines (e.g., clonazepam): Can provide benefit, particularly in patients with associated anxiety 2, 7

Combination Therapy

• If either primidone or propranolol alone do not provide adequate tremor control, they can be used in combination. 2

Critical Contraindications and Precautions

Beta-blockers should be avoided in:

• Chronic obstructive pulmonary disease 1, 5
• Bradycardia 1, 5
• Congestive heart failure 1, 5

Common adverse effects of beta-blockers include:

• Fatigue and depression 1
• Dizziness and hypotension 1
• Exercise intolerance and sleep disorders 1
• Cold extremities and bronchospasm 1
• In elderly patients, excessive heart rate reduction may lead to serious adverse events 1

Botulinum Toxin for Selected Cases

• For disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief 2
• Botulinum toxin in hand muscles can result in bothersome hand weakness and is not widely used 2

Surgical Options for Medication-Refractory Tremor

Surgical therapies should be considered when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, or medical contraindications. 1

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy:

• Shows sustained tremor improvement of 56% at 4 years 1, 3
• Lower complication rate (4.4%) compared to radiofrequency thalamotomy (11.8%) and deep brain stimulation (21.1%) 1, 5
• Early adverse effects include gait disturbance (36%) and paresthesias (38%), which decrease to 9% and 14% respectively by 1 year 1
• Serious adverse events are rare (1.6%) 1
• Contraindications: Cannot undergo MRI, skull density ratio <0.40, bilateral treatment needed, or previous contralateral thalamotomy 1, 5

Deep Brain Stimulation (DBS):

• Provides adjustable, reversible tremor control that can be optimized over time 1
• Preferred for bilateral tremor involvement 1
• Preferred for relatively young patients as it offers an adjustable treatment option 1
• Ventral intermediate nucleus (VIM) of the thalamus is the established target 1
• Provides adequate tremor control in approximately 90% of patients 2

Radiofrequency Thalamotomy:

• Available but carries higher complication risks (11.8%) than MRgFUS 1
• Only rarely done if DBS or focused ultrasound is not possible 6

Treatment Algorithm

1. Initiate treatment only when tremor interferes with function or quality of life 1
2. Start with propranolol (80-240 mg/day) OR primidone 1
3. If inadequate response, try the alternative first-line agent or combine both 2
4. If first-line agents fail, consider topiramate or gabapentin 1, 6
5. For medication-refractory tremor causing significant disability:
   • Unilateral tremor or patients with medical comorbidities: MRgFUS thalamotomy preferred 1
   • Bilateral tremor or contraindications to MRgFUS: DBS 1