Can propranolol be used for breakthrough symptoms of tardive dyskinesia in a patient already on Austedo (deutetrabenazine) and seizure medication?

Propranolol for Breakthrough Tardive Dyskinesia in Patients on Austedo

Propranolol can be used as an adjunctive therapy for breakthrough tardive dyskinesia symptoms in patients already on Austedo (deutetrabenazine), and is generally safe with seizure medications, though careful monitoring for hypotension and bradycardia is essential.

Evidence for Propranolol in Tardive Dyskinesia

Propranolol has demonstrated effectiveness as a treatment option for tardive dyskinesia when primary interventions are insufficient:

• In a retrospective study of 47 patients with TD, propranolol resulted in improvement in 64% of patients, with 77% of responders achieving moderate to complete response at a mean daily dose of only 69 mg 1
• The β-blocker was well-tolerated with only 3 patients (6.4%) discontinuing due to adverse effects (hypotension in 2 patients, nightmares in 1) 1
• Greater severity of TD and longer duration of propranolol therapy were associated with better response 1
• Historical guidelines note that β-blockers have been reported to provide relief for akathisia, suggesting broader utility in movement disorders 2

Rationale for Combination with Austedo

Since Austedo (deutetrabenazine) is already FDA-approved and proven effective for TD, adding propranolol for breakthrough symptoms is reasonable:

• Deutetrabenazine at doses of 24-36 mg/day significantly reduced AIMS scores by 3.2-3.3 points compared to 1.4 points with placebo 3
• The NNT for AIMS response with deutetrabenazine is 5-7, meaning some patients will have incomplete response 4
• Propranolol works through a different mechanism (β-adrenergic blockade) than deutetrabenazine (VMAT2 inhibition), making combination therapy mechanistically sound 1, 4

Safety Considerations with Seizure Medications

The primary concern is additive CNS depression and potential cardiovascular effects, not direct drug-drug interactions:

• Propranolol can lower seizure threshold theoretically, though this is not a major clinical concern at low doses used for TD (typically 60-80 mg/day) 1
• Monitor for hypotension and bradycardia, especially if the patient is on other medications affecting heart rate or blood pressure 1
• Propranolol does not have significant interactions with most common antiepileptic drugs (valproate, levetiracetam, lamotrigine, carbamazepine)
• The main risk is with enzyme-inducing antiepileptics (phenytoin, carbamazepine) which may reduce propranolol levels, potentially requiring dose adjustment

Practical Implementation Algorithm

Start with low-dose propranolol and titrate based on response:

1. Initiate propranolol at 20 mg twice daily (lower than typical antihypertensive doses) 1
2. Check blood pressure and heart rate at baseline and after each dose increase to avoid hypotension 1
3. Increase by 20 mg/day every 3-7 days as tolerated, targeting 60-80 mg/day in divided doses 1
4. Assess TD severity using AIMS score at baseline and every 4 weeks to objectively measure response 2, 5
5. Continue Austedo at current dose unless side effects emerge requiring adjustment 3

Critical Monitoring Parameters

• Blood pressure and heart rate before each dose increase (hold if systolic BP <90 mmHg or HR <50 bpm) 1
• AIMS score every 4 weeks to quantify improvement 2, 5
• Seizure frequency if patient has active epilepsy (though propranolol rarely worsens seizures at these doses)
• Psychiatric symptoms as β-blockers can occasionally cause depression or nightmares 1

When to Reconsider the Approach

Before adding propranolol, ensure Austedo is optimally dosed:

• Austedo can be titrated up to 48 mg/day (24 mg twice daily) if tolerated 3, 4
• If patient is on <36 mg/day of Austedo, consider increasing the primary TD medication first 3
• Only add propranolol if Austedo is at maximum tolerated dose with persistent breakthrough symptoms 6, 1

Alternative Consideration

If propranolol is contraindicated (severe asthma, heart block, severe bradycardia):

• Benzodiazepines have been reported to help with movement disorders, though evidence is limited 2
• Switching the underlying antipsychotic to clozapine or quetiapine (lower D2 affinity) may reduce TD severity if psychiatrically feasible 6, 7