For akathisia due to Abilify (aripiprazole), what do you use: benztropine or propranolol?

Treatment of Akathisia Due to Aripiprazole (Abilify)

Propranolol is the preferred first-line treatment for aripiprazole-induced akathisia, not benztropine. Beta-blockers, particularly propranolol, demonstrate the most consistent efficacy for acute akathisia, while anticholinergic agents like benztropine provide only modest symptomatic relief and are generally less effective 1, 2.

Why Propranolol Over Benztropine

Propranolol has superior evidence for treating akathisia:

• Propranolol is considered the most consistently effective treatment for acute antipsychotic-induced akathisia based on available literature 2
• In open trials, propranolol achieved substantial improvement in all treated patients, with complete remission in 64% of cases (9 of 14 patients) 3
• Response to propranolol occurs rapidly, typically within 24 hours, at relatively low doses of 30-80 mg/day 3
• Recent evidence confirms propranolol remains a first-line treatment, though the overall evidence base is surprisingly modest 1

Benztropine has limited utility for akathisia:

• Benztropine is FDA-approved for extrapyramidal disorders but specifically not for tardive dyskinesia, and its efficacy for akathisia is questionable 4
• Anticholinergic agents like benztropine merely provide symptomatic relief rather than addressing the underlying pathophysiology of akathisia 1
• The FDA label for benztropine does not specifically mention akathisia as an indication, focusing instead on parkinsonism and general extrapyramidal disorders 4

Practical Treatment Algorithm

Step 1: Initiate propranolol

• Start with 10-20 mg three times daily (total 30-60 mg/day) 3
• Titrate up to 80 mg/day if needed based on response 3
• Expect improvement within 24-48 hours 3
• Monitor for hypotension, bradycardia, and contraindications (asthma, heart block, heart failure) 1

Step 2: If propranolol fails or is contraindicated

• Add a benzodiazepine (e.g., lorazepam 0.5-1 mg twice daily) for subjective distress 2
• Consider low-dose mirtazapine (7.5-15 mg at bedtime) as an alternative with strong evidence for 5-HT2a antagonism 1

Step 3: If both fail

• Trial amantadine or clonidine 2
• Consider gabapentin or pregabalin as voltage-gated calcium channel blockers 5

Important Clinical Caveats

Aripiprazole-specific considerations:

• Aripiprazole can induce akathisia even though it causes minimal other extrapyramidal symptoms 5
• Akathisia from aripiprazole may occur despite its partial dopamine agonist properties 6
• Switching from aripiprazole to another antipsychotic may be necessary if akathisia persists despite treatment 6

Propranolol contraindications to screen for:

• Asthma or reactive airway disease (absolute contraindication) 1
• Cardiogenic shock, sinus bradycardia, or heart block greater than first degree 1
• Hypotension or decompensated heart failure 1

Common pitfall: Do not assume benztropine will work simply because it treats other extrapyramidal symptoms—akathisia has a different pathophysiology involving noradrenergic-dopaminergic imbalance rather than pure dopamine blockade 5. Anticholinergics address parkinsonian symptoms but not the restlessness of akathisia 1.

Monitoring strategy:

• Assess response within 24-48 hours of starting propranolol 3
• If no improvement by 72 hours at adequate doses (60-80 mg/day), proceed to Step 2 2
• Maintain high suspicion in patients who cannot verbalize symptoms (e.g., those with severe psychosis or cognitive impairment) 5