What is the best treatment for akathisia?

Treatment of Akathisia

Propranolol (10-30 mg two to three times daily) is the most consistently effective first-line pharmacological treatment for akathisia, combined with reducing the antipsychotic dose or switching to a lower-risk agent like quetiapine or olanzapine. 1, 2

Immediate Management Algorithm

Step 1: Adjust the Causative Medication

• Reduce the current antipsychotic dosage while maintaining therapeutic range, or switch to an antipsychotic with lower akathisia risk such as quetiapine or olanzapine 1, 2
• Avoid antipsychotic polypharmacy, which increases side effect burden 1, 2
• Critical pitfall: Akathisia is frequently misinterpreted as psychotic agitation or anxiety, leading clinicians to inappropriately increase antipsychotic doses, which worsens the condition 1, 2

Step 2: Initiate Propranolol as First-Line Pharmacotherapy

• Propranolol 10-30 mg two to three times daily is the most consistently effective treatment with the strongest evidence base 1, 2, 3, 4
• Other lipophilic beta-blockers are acceptable alternatives if propranolol is contraindicated 3
• Contraindications to consider: asthma, bradycardia, orthostatic hypotension 5
• In patients with high cardiovascular risk, carefully consider QT-prolonging effects when switching antipsychotics 1, 2

Second-Line Treatment Options (When Beta-Blockers Fail or Are Contraindicated)

Benzodiazepines

• Clonazepam can provide symptomatic relief and address the anxiety component of akathisia in patients who do not respond to first-line treatments 1
• Particularly useful if subjective distress persists despite beta-blocker therapy 3

5-HT2A Receptor Antagonists

• Mirtazapine (7.5-15 mg once daily) has demonstrated compelling evidence for therapeutic efficacy and represents a newer treatment approach 4, 5
• Other agents with 5-HT2A antagonism (trazodone, mianserin) show promise but have less robust evidence 5, 6

Anticholinergic Agents

• Notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed 1
• Benztropine 1-4 mg once or twice daily can be used, particularly for acute dystonic reactions, but monitor for anticholinergic side effects 1, 7
• When extrapyramidal disorders develop soon after neuroleptic initiation, they are often transient; withdraw after 1-2 weeks to determine continued need 7

Third and Fourth-Line Options

• Clonidine can be tried if beta-blockers and benzodiazepines are unsuccessful 3
• Amantadine is considered a fourth-line option with limited evidence 1, 3
• Vitamin B6, gabapentin, and pregabalin have insufficient current evidence despite promising exploratory reports 4

Special Populations and Critical Considerations

Children and Adolescents

• Higher risk for extrapyramidal side effects including akathisia compared to adults 1, 2
• Monitor carefully for anticholinergic side effects when using anticholinergic agents 1

SSRI-Induced Akathisia

• SSRI-induced akathisia is associated with increased suicidality, particularly with fluoxetine 8, 2
• Systematically inquire about suicidal ideation before and after treatment initiation 8, 2
• Be especially alert to the possibility of suicidality if SSRI treatment is associated with onset of akathisia 8

Emergency Settings

• For acute akathisia, intramuscular administration of medications is preferred over intravenous route 1
• In acute dystonic reactions, benztropine 1-2 mL injection usually relieves the condition quickly 7

Evidence Quality Considerations

The recommendation for propranolol as first-line treatment is based on consistent findings across multiple guidelines 1, 2 and research studies 3, 4, 5, though the overall evidence base is described as "modest" 5. The emerging evidence for mirtazapine represents a promising alternative with potentially better tolerability 4, 5. Anticholinergics, despite widespread use, have limited efficacy specifically for akathisia 1, distinguishing this condition from other extrapyramidal symptoms.