Medications for essential tremor

Clinical question

How effective are β-blockers and other first-line agents for essential tremor?

Bottom line

Older, small randomized controlled trials (RCTs) show that propranolol reduces tremor severity (about 2 points more than placebo on 10- to 15-point scales) and leads to patients feeling “definitely better” in 64% to 100% versus 14% to 20% (placebo) at 2 to 6 weeks. Benefit is seen from 90 mg/day, with 120 to 240 mg/day most studied. Primidone and topiramate may improve function based on limited RCTs.

Evidence

Results are statistically significant unless stated. No systematic reviews of patient-oriented outcomes were found. Patient-reported outcomes from double-blind, placebo-controlled RCTs, mainly in upper limb tremor, are described.

• Propranolol:

  • -Tremor (patient-rated): 9 of 9 RCTs report benefit over placebo.¹ For example, the proportion of patients “definitely better” at 2 to 6 weeks was 100% versus 20% (placebo) in an RCT (N=10), number needed to treat (NNT)=2 (PEER calculation)²; and 64% versus 14% (placebo) in another RCT (N=7), NNT=2.³

  • -Severity on 10- to 15-point scales (baseline scores not provided): At 2 to 3 weeks in 3 RCTs (N=9 to 23), placebo score 5 to 12 points; propranolol about 1.6 to 2.0 points better than placebo, likely clinically meaningful. Two RCTs were statistically different; 1 was not.^4-6

  • -Function: no difference.⁷

• Sotalol: 2 RCTs (N=9 to 17) measured tremor (scale of 0 to 100, baseline score=34). At 14 days, placebo score=31. Sotalol was 9 points better than placebo, likely clinically meaningful.⁸ Other RCT was similar.⁴

• Metoprolol and atenolol:

  • -Symptoms: no difference from placebo.^4,6,8

  • -Metoprolol: inferior to propranolol.⁶ For example, at 14 days, metoprolol tremor score=4.8 on a 10-point scale. Propranolol score was 1.5 points better.

• Primidone: Two RCTs (N=22 each)¹ examined functional rating (lower=better, baseline=8). After 4 weeks, placebo score=7.8 on a 15-point scale. Primidone was 2.6 points lower (statistics not reported); likely clinically meaningful.

• Topiramate (largest RCT [N=223])¹ had a good or very good outcome: 69% versus 15% (placebo), NNT=3.

• Limitations:

  • -Many RCTs and systematic reviews report tremor amplitude or frequency but clinical significance is unclear.⁹

  • -Patient- and clinician-rated symptom improvement differ.

  • -Numerous symptom scales (many unvalidated) were used, and reporting was frequently incomplete.

Context

• Guidelines: Propranolol, topiramate, and primidone are first line.¹⁰ Other options include alprazolam, gabapentinoids (inconsistent benefit), and botulinum toxin.

• Indirect comparisons: Propranolol showed greater efficacy than all treatments except deep brain stimulation.⁹

Implementation

Essential tremor is 1 of the most common movement disorders and can affect quality of life.¹⁰ Propranolol is most common agent, with consistent symptom improvement across double-blind, placebo-controlled RCTs.¹ Dosing starts at 10 to 20 mg twice a day and is titrated based on response, with similar benefits across 90 to 320 mg/day.^3-5 Although no RCTs assess as-needed use, objective improvement is seen with single doses.³ Common adverse effects are headache, dizziness, bradycardia, and hypotension. Topiramate and primidone are effective but limited by side effects.