What is the recommended treatment for orthostatic tremor?

Treatment of Orthostatic Tremor

Clonazepam and gabapentin are the first-line pharmacological treatments for orthostatic tremor, with gabapentin showing 60-80% improvement in patients and being effective even in those who failed clonazepam therapy. 1, 2, 3

Understanding Orthostatic Tremor

• Orthostatic tremor is characterized by unsteadiness on standing due to a high-frequency tremor (13-18 Hz) involving the legs, which rapidly improves upon sitting or walking 2
• Symptoms typically begin in the sixth decade of life and can significantly impact quality of life due to the strong need to sit down or move to avoid standing still 2
• Diagnosis requires polygraphic recording confirming a fast and synchronous tremor of the legs between 13-18 Hz 2
• The pathophysiology involves a ponto-cerebello-thalamo-cortical network, though the exact dysfunction remains incompletely understood 3

First-Line Pharmacological Treatment Options

• Gabapentin is highly effective for orthostatic tremor with reported improvement of 60-80% (mean 73%) at doses ranging from 300-1800 mg/day (mean 1030 mg/day) 1
• Clonazepam is widely used as a first-line agent, though efficacy may be inconsistent and some patients fail to respond 2, 3
• Lower starting doses and more gradual titration of gabapentin may reduce adverse effects, especially in older individuals 4

Second-Line and Alternative Treatment Options

• Dopaminergic medications may be helpful in some patients with orthostatic tremor, particularly those with concurrent Parkinson's disease 4
• Perampanel, a novel AMPA receptor antagonist, has shown promising results with one case reporting 90% subjective improvement at doses of 1-2 mg/day 5
• For medication-refractory cases, deep brain stimulation of the ventral intermediate nucleus of the thalamus has shown promise 3

Treatment Algorithm

1. Start with either gabapentin (initial dose 300 mg/day, gradually titrate to 300-1800 mg/day based on response) or clonazepam 1, 2
2. If the initial medication is ineffective or poorly tolerated, switch to the alternative first-line agent 3
3. For partial response, consider combination therapy with both gabapentin and clonazepam 3
4. For patients with inadequate response to first-line treatments, consider:
   • Dopaminergic medications, especially if Parkinson's features are present 4, 2
   • Trial of perampanel (starting at 1 mg/day) 5
   • Referral for deep brain stimulation evaluation in medication-refractory cases 3

Important Clinical Considerations

• Distinguish orthostatic tremor from orthostatic hypotension, which requires different management approaches 4
• Side effects of gabapentin are generally mild, transient, and dose-related 1
• Treatment benefit for orthostatic tremor is often modest and inconsistent across patients, requiring trials of different medications 3
• The response to treatment is often disappointing compared to other movement disorders, highlighting the need for individualized medication trials 2