Essential Tremor: What We Can Learn from Current Pharmacotherapy

William Ondo

doi:10.5334/tohm.318

Figures & Tables

Table 1

Summary

Drugs Listing in Descending Efficacy for Tremor (+++ to Worsen)¹	Open GABA Receptors	Increase GABA Synthesis	Inhibit GABA Metabolism Reuptake	Inhibit NA Channel	Inhibit Ca Channels	Inhibit GlutamateTransmission	Carbonic Anhydrase Inhibitor	Other
+++
Ethanol	+++
Topiramate	++?	++?	++?	++	++	++ AMPA	+
Primidone	++?			++
++
Benzodiazepines	+++
Phenobarbital	+++				+	+ AMPA
+
Gabapentin		+ GAD?			+++ α2γ
Pregabalin					+++ α2γ
Zonisamide				++	++ LVA		+
Levetiracetam	+	+?	+?	+		+ AMPA		SV2A
Acetazolamide							+++
TPA023	+++ α2,3
No effect
Lamotrigine				+++	++ HVA
Phenytoin				+++
Carbamazepine				+++
Oxcarbazepine				+++
Lacosamide¹^,²				+++
Worsen
Valproate		++		++	++ LVA
Unknown
Felbamate	+			++	++	+ NMDA
Tiagabine²			+++ (GAT)
Vigabatrin			+++GABA-T
Ethosuximide¹^,²					+++ LVA
Perampanel						+++ AMPA
Stiripentol	+++ α3
Rufinamide²				+++
Retigabine² (ezogabine)		+						KCNQ2/3

Abbreviations: α2Δ, Alpha-2 Delta Subunit of Calcium Channel; AMPA, Alpha-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid; GABA, Gamma-Aminobutyric Acid; GABA-T, GABA Transaminase (GABA metabolism) Vigabatrin; GAD, Glutamate Decarboxylase Activity Increased to Increase GABA; GAT, GABA Transporter-1 (GABA reuptake) Tiagabine; HVA, High-Voltage Activated Calcium Channel Receptor (L, P, N types); KCNQ2/3, Voltage-Gated Potassium Channels, Activating M-current; LVA, Low-Voltage Activated Calcium Channel Receptor (T-type); NMDA, N- Methyl-d-Aspartate; SV2A, Synaptic Vesicle Glycoprotein.

1 Efficacy based on authors’ expert opinion: +++, consistent efficacy in controlled trials; ++, inconsistent controlled data and/or consistent positive open label reports; +, any positive report of efficacy without preponderance of data suggesting a lack of effect.

2 ‘Tremor listed as adverse events in >10% or reported to worsen tremor in small trials.

Table 2

Summary of Beta Blockers

	Typical Dose Daily mg/frequency	Lipid Solubility	Sympathetic Activity	Beta-1 Activity	Beta-2 Activity	Tremor Efficacy
Propranolol	40–320/bid	+++	−	+	+	+++
Arotinolol	10–40/bid?	+	−	+	+	+++
Nadolol	80–240/qd	+++	−	+	+	+++
Sotalol	80–320/bid	+	−	+	+	+++
Timolol	10–20/bid	++	±	+	+	++
Metoprolol	100–200/bid	++	−	+	±	++
Atenolol	50–100/qd	+	−	+	±	+
Pindolol	10–30/bid	++	+	+	+	−

[i] Abbreviations: bid, Twice a Day; qd, Every Day.

[ii] Propranolol ≤ arotinolol; propranolol ≥ metoprolol (doses where metoprolol loses B1 selectivity); propranolol > atenolol; propranolol >> pindolol.