How is iatrogenic (induced by medical intervention) tremor best managed?

Management of Iatrogenic Tremor

Iatrogenic tremor should be managed by first identifying and discontinuing or reducing the offending medication when possible, followed by symptomatic treatment with propranolol (80-240 mg/day) or primidone as first-line agents if tremor persists and significantly impacts function. 1

Identify and Address the Causative Agent

The cornerstone of managing iatrogenic tremor is identifying the medication or intervention causing the tremor. Common culprits include:

• Stimulants and sympathomimetics that increase catecholamine release 2
• Valproate, lithium, corticosteroids, and certain antidepressants 3
• Caffeine and other substances that can enhance physiologic tremor 4, 2

When medically feasible, discontinue or reduce the dose of the offending agent. This is the most direct approach and may resolve the tremor entirely without need for additional treatment. 2

Pharmacological Management When Tremor Persists

If the causative medication cannot be discontinued or if tremor persists despite dose reduction:

First-Line Treatment

Propranolol (80-240 mg/day) is the most established first-line treatment, having been used for over 40 years with demonstrated efficacy in up to 70% of patients. 1, 4 This beta-blocker is particularly effective for postural and action tremors. 4

Primidone is an equally effective first-line alternative, though clinical benefits may not become apparent for 2-3 months, so an adequate trial period is essential. 1 Therapeutic benefit can occur even when derived phenobarbital levels remain subtherapeutic, confirming primidone itself has anti-tremor properties. 1

Important Contraindications and Precautions

Avoid beta-blockers in patients with:

• Chronic obstructive pulmonary disease 1, 4
• Bradycardia 1, 4
• Congestive heart failure 1, 4

Common adverse effects of beta-blockers include fatigue, depression, dizziness, hypotension, exercise intolerance, sleep disorders, cold extremities, and bronchospasm. 1 In elderly patients, excessive heart rate reduction may lead to serious adverse events. 1, 4

For primidone, counsel women of childbearing age about teratogenic risks (neural tube defects), and monitor for behavioral disturbances, irritability, and sleep disturbances, particularly at higher doses. 1

Second-Line Options

If first-line agents fail or are contraindicated:

• Nadolol (40-320 mg daily) - alternative beta-blocker with evidence for tremor control 1, 4
• Metoprolol (25-100 mg extended release daily or twice daily) 1, 4
• Gabapentin - has limited evidence for moderate efficacy 1, 4

Non-Pharmacological Approaches

Lifestyle modifications are particularly important for enhanced physiologic tremor:

• Avoid strenuous exercise before precision tasks 4, 2
• Reduce caffeine consumption 4, 2
• Implement stress reduction techniques 4, 2

Rhythm modification techniques can provide additional benefit:

• Superimpose alternative voluntary rhythms on top of the existing tremor and gradually slow all movement to complete rest 5, 4
• For unilateral tremor, use the unaffected limb to dictate a new rhythm (tapping/opening and closing the hand) to entrain the tremor to stillness 5, 4
• Use gross rather than fine movements for activities like handwriting (marker on large paper rather than normal handwriting) 5, 4
• Assist the person to relax muscles in the limb to prevent cocontraction 5

Critical Pitfall to Avoid

Do not prescribe aids and equipment in the acute phase, as they may interrupt normal automatic movement patterns and cause maladaptive functioning. 5 If aids are necessary for safety (e.g., safe hospital discharge), they should be considered short-term solutions with a minimalist approach and a clear plan to progress toward independence. 5

Surgical Options for Refractory Cases

Surgical therapies should be considered when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, or medical contraindications. 1

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy shows sustained tremor improvement of 56% at 4 years with the lowest complication rate (4.4%) compared to radiofrequency thalamotomy (11.8%) and deep brain stimulation (21.1%). 1, 4 However, MRgFUS is contraindicated bilaterally, in patients unable to undergo MRI, or those with skull density ratio <0.40. 1, 4

Deep brain stimulation (DBS) is preferred for bilateral tremor or when MRgFUS is contraindicated, offering adjustable and reversible tremor control. 1

Treatment Algorithm

1. Identify and discontinue/reduce the offending medication when medically feasible 2
2. If tremor persists and impacts function, initiate propranolol (80-240 mg/day) or primidone 1, 4
3. If first-line agents fail or are contraindicated, trial second-line medications (nadolol, metoprolol, or gabapentin) 1, 4
4. For severe, medication-refractory tremor, consider surgical options: MRgFUS for unilateral tremor or DBS for bilateral involvement 1, 4