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.

Tools for Practice articles are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice@cfpc.ca.