#397 Meds for Essential Tremor: Steady solution or shaky science?
CLINICAL QUESTION
How effective are beta-blockers and other first line agents for essential tremor?
BOTTOM LINE
Older, small randomized controlled trials (RCTs) show that propranolol improves tremor severity (~2-points more than placebo on 10–15-point scales) and leads to feeling “definitely better” in 64-100% versus 14-20% (placebo) at 2-6 weeks. Benefit is seen from 90 mg/day, with 120–240 mg/day most studied. Primidone and topiramate may improve function based on limited RCTs.
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EVIDENCE
- Results statistically significant unless stated.
- Systematic reviews of patient-oriented outcomes not found. Patient-reported outcomes from double-blind, placebo-controlled RCTs, mainly in upper limb tremor, described here.
- Propranolol:
- Tremor (patient-rated): 9 of 9 RCTs report benefit over placebo. Examples:1-9
- Proportion of patients “definitely better” at 2-6 weeks:
- RCT (10 patients): 100% versus 20% placebo, number needed to treat (NNT)=2 (PEER calculation).1
- RCT (7 patients): 64% versus 14% placebo,2 NNT=2.
- Severity on 10-15 point scales (baseline scores not provided). At 2-3 weeks:
- Three RCTs (9-23 patients): Placebo score 5-12 points. Propranolol ~1.6-2.0 points better than placebo, likely clinically meaningful. Two RCTs statistically different; one not.3-5
- Proportion of patients “definitely better” at 2-6 weeks:
- Function: No difference.6
- Tremor (patient-rated): 9 of 9 RCTs report benefit over placebo. Examples:1-9
- Sotalol: Two RCTs (9-17 patients).
- Tremor (scale: 0-100, baseline: 34): At 14 days, placebo score: 31. Sotalol: 9 points better than placebo, likely clinically meaningful.10 Other RCT similar.3
- Metoprolol, atenolol:
- Symptoms: No difference from placebo.3,5,9,10
- Metoprolol: Inferior to propranolol.5,11 Example: At 14 days, metoprolol tremor score 4.8 on 10-point scale. Propranolol 1.5 points better.
- Primidone: Two RCTs (22 patients each).12,13
- Functional rating (lower=better function, baseline=8). After four weeks, placebo score=7.8 on 15-point scale. Primidone 2.6 points lower (statistics not reported), likely clinically meaningful.
- Topiramate: Largest RCT (223 patients).14
- “Good/very good outcome:” 69% versus 15% placebo, NNT=3.
- Limitations:
- Many RCTs/systematic reviews report tremor amplitude/frequency but clinical significance unclear.15
- Patient and clinician-rated symptom improvement differ.
- Numerous symptom scales (many unvalidated), frequent incomplete reporting.
- Many RCTs/systematic reviews report tremor amplitude/frequency but clinical significance unclear.15
CONTEXT
- Guidelines: Propranolol, topiramate and primidone first-line.16,17
- Options: Alprazolam,18 gabapentinoids (inconsistent benefit),6,19-23 botulinum toxin.24
- Propranolol dosing:
- Lower doses (possibly as low as 90mg/day) similarly effective to higher (320mg)2,4,5
- “As needed”: No RCTs.
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Well done. Thank you
Interesting
I often do not start at this high a dose of propranolol
very useful
Good information.