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, with the American Academy of Neurology recommending either agent as initial therapy, effective in up to 70% of patients. 1

When to Initiate Treatment

• Medications should only be started when tremor symptoms interfere with function or quality of life 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 (Preferred Beta-Blocker)

• Dosage: 80-240 mg/day 1, 3
• Most established medication with over 40 years of demonstrated efficacy 4, 1
• Reduces tremor severity by approximately 50% in responsive patients 2, 5
• Contraindications: Avoid in chronic obstructive pulmonary disease, bradycardia, or congestive heart failure 1, 6
• Common adverse effects: Fatigue, depression, dizziness, hypotension, exercise intolerance, sleep disorders, cold extremities, and bronchospasm 1
• Drug interactions: Caution with CYP2D6, 1A2, or 2C19 inhibitors; increases warfarin concentration requiring prothrombin time monitoring; additive effects with calcium channel blockers and digitalis causing bradycardia and heart block 7
• Dual benefit: For patients with both essential tremor and hypertension, propranolol addresses both conditions simultaneously 1, 6

Primidone (Alternative First-Line)

• Equally effective as propranolol as first-line therapy 1
• Anti-tremor properties occur even when derived phenobarbital levels remain subtherapeutic, confirming primidone itself has direct tremor-reducing effects 1
• Clinical benefits may not appear for 2-3 months, requiring an adequate trial period 1
• Adverse effects: Behavioral disturbances, irritability, sleep disturbances (particularly at higher doses) 1
• Teratogenic risk: Women of childbearing age must be counseled about neural tube defects 1

Combination Therapy

• If either propranolol or primidone alone provides inadequate control, they can be used in combination 2

Alternative Beta-Blockers (If Propranolol Not Tolerated)

• 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; common adverse effects include fatigue, depression, nausea, dizziness, insomnia 1

Second-Line Medications

When First-Line Agents Fail

• Topiramate: Established efficacy for essential tremor 8
• Gabapentin: Limited evidence for moderate efficacy 1, 2
• Benzodiazepines (e.g., clonazepam): Can provide benefit, particularly in patients with associated anxiety 2, 5

Carbamazepine

• May be used as second-line therapy, though generally not as effective as first-line options 1

Botulinum Toxin Injections

• Indicated for: Disabling head or voice tremor 2
• Not widely used for hand tremor due to bothersome hand weakness 2

Surgical Interventions for Medication-Refractory Tremor

Indications for Surgery

• Consider when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, medical contraindications, or occupational limitations 1
• Surgical options provide tremor control in approximately 90% of patients 2

Treatment Algorithm for Surgical Candidates

For unilateral tremor or patients with medical comorbidities:

• Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy is preferred 1, 3
  • Sustained tremor improvement of 56% at 4 years 1, 6
  • Lowest complication rate: 4.4% compared to radiofrequency thalamotomy (11.8%) and DBS (21.1%) 1, 6
  • Early adverse effects: gait disturbance (36%) and paresthesias (38%), decreasing to 9% and 14% by 1 year 1
  • Serious adverse events rare (1.6%), with most being mild or moderate (98.4%) and >50% resolving by 1 year 1
  • Contraindications: Cannot undergo MRI, skull density ratio <0.40, bilateral treatment needed, or previous contralateral thalamotomy 1, 6

For bilateral tremor:

• Deep Brain Stimulation (DBS) is the procedure of choice 1, 2
  • Ventral intermediate nucleus (VIM) of thalamus is the established target 1
  • Provides adjustable, reversible tremor control that can be optimized over time 1
  • Preferred for relatively young patients as it offers adjustable treatment 1
  • Complication rate: 21.1% 1
  • Bilateral ablative procedures should be avoided due to higher adverse effects; DBS is safer for bilateral intervention 2

For patients with contraindications to both MRgFUS and DBS:

• Radiofrequency thalamotomy available but carries higher complication risk (11.8%) 1

Important Clinical Pitfalls

• Elderly patients: Excessive heart rate reduction with beta-blockers may lead to serious adverse events 1
• Alcohol interaction: Concomitant use with propranolol may increase plasma levels 7
• NSAIDs: May blunt the antihypertensive and heart rate-reducing effects of propranolol 7
• Epinephrine: Not indicated in propranolol overdose due to risk of uncontrolled hypertension from unopposed alpha-receptor stimulation 7
• Primidone trial duration: Must allow 2-3 months before determining efficacy 1
• DBS vs. thalamotomy: DBS and thalamotomy have comparable efficacy, but DBS has fewer complications, particularly for bilateral procedures 2

Non-Pharmacological Approaches

• Rhythm modification techniques: Superimposing alternative rhythms on existing tremor and gradually slowing movement to complete rest 1
• For unilateral tremor: Using the unaffected limb to dictate a new rhythm can help entrain tremor to stillness 1
• Movement strategies: Using gross rather than fine movements, especially for activities like handwriting 1
• Avoid: Cocontraction or tensing of muscles as this is not a helpful long-term strategy 1
• Lifestyle modifications: Avoiding strenuous exercise before precision tasks, reducing caffeine consumption, implementing stress reduction techniques 3