Management of Tremor in a Patient on Multiple Psychotropic Medications
The most likely culprit is valproate (Depakote), and the first-line treatment is propranolol, which has been clearly demonstrated to be the most effective agent for valproate-induced tremor. 1
Identify the Causative Agent
The tremor is most likely medication-induced, with valproate being the primary suspect:
Valproate causes symptomatic tremor in approximately 10% of patients, typically appearing within one month of starting therapy and usually at dosages greater than 750 mg per day 2. This patient is on 1000 mg daily (500mg bid), placing him at significant risk.
The tremor from valproate is similar to essential tremor—present at rest and exacerbated by action or antigravity positioning 2. There is no close correlation between tremor severity and plasma valproate levels 2.
Lamotrigine can also induce tremor in 4-25% of patients (depending on detection method), particularly affecting postural and intentional movements via cerebellar pathways 3. However, at only 25mg daily, this patient is on a very low dose, making lamotrigine a less likely primary cause.
The combination of valproate and lamotrigine together can produce disabling tremors, including resting-type tremors that progressively worsen 4. This synergistic effect should be strongly considered given this patient's medication regimen.
Aripiprazole (Abilify) can cause tremor as an extrapyramidal side effect, but this typically presents differently than the tremor pattern associated with valproate 5.
Buspirone at 10mg bid is within normal dosing range and is not commonly associated with tremor 6, 7.
Treatment Algorithm
First-Line: Propranolol
Propranolol is clearly the most therapeutic agent for valproate-induced tremor based on accelerometric recordings in 19 patients 1.
Start propranolol at 20-40mg twice daily and titrate as needed, monitoring for bradycardia and hypotension.
Propranolol has established efficacy at dosages of 80-240 mg/day for various tremor conditions 8.
Second-Line: Amantadine
Amantadine was moderately effective for valproate tremor in controlled studies, though significantly less effective than propranolol 1.
Consider if propranolol is contraindicated (asthma, severe bradycardia, heart block).
Medication Adjustment Strategy
If propranolol provides insufficient relief:
Consider reducing valproate dosage if seizure control or mood stabilization permits, as tremor severity often correlates with doses above 750mg/day 2.
Evaluate whether lamotrigine can be discontinued, as the combination of valproate and lamotrigine has been specifically implicated in disabling tremors that resolved within 2.5 months after discontinuation 4.
If both valproate and lamotrigine are essential for psychiatric stability, prioritize discontinuing or reducing valproate first, as it is the more common tremor culprit 1, 2.
Agents to Avoid
Cyproheptadine, diphenhydramine, and benztropine provide little or no relief for valproate-induced tremor 1.
Do not add anticholinergic agents empirically, as they are ineffective for this specific tremor type 1.
Important Caveats
Check serum valproate levels to ensure the patient is not supratherapeutic, though tremor can occur even at therapeutic levels 2.
Assess for vitamin B12 deficiency, as low B12 levels may potentiate drug-induced movement disorders, particularly with concurrent use of valproate and other psychotropics 5.
Document tremor characteristics carefully: valproate tremor is present at rest and worsens with action, while lamotrigine tremor primarily affects postural and intentional movements 3, 2.
If tremor is unilateral or has atypical features, consider alternative diagnoses or contributing factors beyond medication effects 5.