What are the treatment options for akathisia?

Treatment of Akathisia

For akathisia, first reduce the antipsychotic dose or switch to quetiapine or olanzapine, and simultaneously initiate propranolol 10-30 mg two to three times daily as the most consistently effective pharmacological treatment. 1, 2

Immediate Management Algorithm

Step 1: Antipsychotic Modification (First Priority)

• Reduce the current antipsychotic dosage while maintaining therapeutic range, as dose reduction can potentially manage akathisia 1
• Switch to an antipsychotic with lower akathisia risk, specifically quetiapine or olanzapine 1, 2
• Avoid antipsychotic polypharmacy, which increases side effect burden 2
• Critical pitfall: Akathisia is frequently misinterpreted as psychotic agitation or anxiety, leading clinicians to inappropriately increase antipsychotic doses, which worsens the condition 2, 3

Step 2: First-Line Pharmacological Treatment

• Propranolol 10-30 mg two to three times daily is the most consistently effective treatment for akathisia 1, 2, 4, 5
• This beta-blocker has the strongest evidence base among all adjunctive treatments 4, 6
• In patients with high cardiovascular risk, carefully consider QT-prolonging effects when switching antipsychotics 2, 3
• Contraindications include asthma, bradycardia, and orthostatic hypotension 6

Second-Line Treatment Options (When Propranolol Fails or Is Contraindicated)

Benzodiazepines

• Clonazepam can provide symptomatic relief and address the anxiety component of akathisia 2, 5
• This is a sensible next choice when beta-blockers fail, especially if subjective distress persists 4

Anticholinergic Agents

• Benztropine 1-4 mg once or twice daily may be tried, though it is notably less effective for akathisia compared to other extrapyramidal side effects 2, 7
• Monitor for anticholinergic side effects, especially in children and adolescents 2
• Despite being commonly prescribed, anticholinergics have limited efficacy specifically for akathisia 2

Third-Line and Alternative Options

Serotonin 5-HT2A Antagonists

• Mirtazapine (7.5-15 mg once daily) has demonstrated compelling evidence for therapeutic efficacy 6, 5
• Other 5-HT2A antagonists (trazodone, mianserin) have shown promise but with less robust evidence 6, 5

Additional Agents (Limited Evidence)

• Clonidine can be tried if beta-blockers and benzodiazepines are unsuccessful 4, 5
• Amantadine is considered a fourth-line option with limited evidence 2, 4
• Vitamin B6, gabapentin, and pregabalin have insufficient current evidence 5, 8

Special Population Considerations

Children and Adolescents

• Higher risk for extrapyramidal side effects including akathisia compared to adults 2, 3
• Young age and male gender are additional risk factors for acute dystonic reactions 2
• Careful monitoring for anticholinergic side effects is essential when using anticholinergic agents 2

SSRI-Induced Akathisia

• SSRI-induced akathisia is associated with increased suicidality, particularly with fluoxetine 2, 3
• Systematically inquire about suicidal ideation before and after treatment initiation 2, 3
• Be especially alert to the possibility of suicidality if SSRI treatment is associated with onset of akathisia 2

Monitoring and Prevention

Pre-Treatment Assessment

• Systematically assess akathisia with a validated scale before starting antipsychotics and during dosage titration 8

Prophylactic Considerations

• Prophylactic antiparkinsonian agents may be considered in high-risk patients, particularly those with history of dystonic reactions or compliance concerns 2
• The need for antiparkinsonian agents should be reevaluated after the acute phase, as many patients no longer require them during long-term therapy 2

Duration of Treatment

• After one or two weeks of treatment for drug-induced extrapyramidal disorders, the medication should be withdrawn to determine continued need 7
• If disorders recur, treatment can be reinstituted 7