What are the treatment options for akathisia?

Treatment of Akathisia

The first-line treatment for akathisia is lowering the antipsychotic dose or switching to a lower-risk agent (quetiapine or olanzapine), with propranolol 10-30 mg two to three times daily as the most consistently effective pharmacological rescue agent. 1

Initial Management Strategy

The priority is modifying the causative medication before adding rescue agents:

• Reduce the antipsychotic dosage while staying within therapeutic range, as this directly addresses the underlying cause 1
• Switch to an antipsychotic with lower akathisia risk such as quetiapine or olanzapine if dose reduction is insufficient 1
• Avoid antipsychotic polypharmacy, which increases side effect burden and can worsen akathisia 1

Critical Diagnostic Pitfall

• Akathisia is frequently misinterpreted as psychotic agitation or anxiety, leading clinicians to inappropriately increase antipsychotic doses—this worsens the condition 1
• Systematically distinguish akathisia from psychiatric symptoms before escalating treatment 1

Pharmacological Treatment Algorithm

When medication adjustment is not feasible or insufficient, follow this evidence-based hierarchy:

First-Line Pharmacological Agent

• Propranolol 10-30 mg two to three times daily is the most consistently effective treatment across multiple studies 1, 2
• Propranolol has contraindications including asthma, bradycardia, and orthostatic hypotension that limit use in some patients 3

Second-Line Options

• Mirtazapine 7.5-15 mg once daily has compelling evidence as an alternative first-line agent, particularly when beta-blockers are contraindicated 4, 3
• Mirtazapine works through serotonin 5-HT2a receptor antagonism and demonstrates strong efficacy at low doses 3

Third-Line Options

• Benzodiazepines (clonazepam) provide symptomatic relief and address the anxiety component, particularly useful when subjective distress persists despite other treatments 1, 2
• Consider benzodiazepines when beta-blockers fail or as adjunctive therapy 2

Fourth-Line Options

• Anticholinergic agents are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed 1
• Monitor carefully for anticholinergic side effects, especially in children and adolescents 1

Fifth-Line Options

• Amantadine is a mild dopaminergic agent with limited evidence, reserved for refractory cases 1, 2
• Clonidine can be tried when all other agents fail 2

Special Population Considerations

SSRI-Induced Akathisia

• SSRI-induced akathisia, particularly with fluoxetine, is associated with increased suicidality 1
• Systematically inquire about suicidal ideation before and after SSRI initiation, and be especially vigilant if akathisia develops during treatment 1

Pediatric Patients

• Children and adolescents face higher risk for extrapyramidal side effects including akathisia 1
• Monitor more carefully for anticholinergic side effects when using anticholinergic agents in this population 1

Emergency Settings

• In acute akathisia requiring parenteral administration, prefer intramuscular over intravenous route 1

Cardiovascular Risk Patients

• Carefully consider QT-prolonging effects when switching antipsychotics in patients with high cardiovascular risk 1

Treatment-Resistant Cases

When standard approaches fail, consider rotation between different pharmacological strategies:

• Voltage-gated calcium channel blockers (gabapentin, pregabalin) may provide relief 5
• Other serotonin 5-HT2a antagonists (cyproheptadine, trazodone) have shown promise but require more evidence 3
• Chronic and tardive akathisia may persist after drug withdrawal and prove resistant to standard treatments 5