How to treat antipsychotic-induced akathisia?

Treatment of Antipsychotic-Induced Akathisia

The first-line approach to antipsychotic-induced akathisia is dose reduction of the current antipsychotic, followed by switching to quetiapine or olanzapine, or adding propranolol 10-30 mg two to three times daily. 1

Algorithmic Treatment Approach

Step 1: Dose Reduction

• Reduce the antipsychotic dose while remaining within the therapeutic range as the initial intervention. 1
• This addresses the root cause by decreasing dopamine D2 receptor blockade without compromising psychotic symptom control. 1

Step 2: Switch Antipsychotic

• If dose reduction is insufficient or not feasible, switch to quetiapine or olanzapine, which have lower akathisia liability. 1
• These antipsychotics have more favorable receptor binding profiles that reduce extrapyramidal side effects. 2

Step 3: Add Propranolol

• If switching is not appropriate, add propranolol 10-30 mg two to three times daily as adjunctive treatment. 1, 3
• Propranolol is the most consistently effective pharmacological treatment for akathisia, though evidence is modest. 4, 5
• Contraindications include asthma, bradycardia, and orthostatic hypotension. 4

Step 4: Alternative Adjunctive Medications (if propranolol fails or is contraindicated)

Based on the highest quality 2024 network meta-analysis, the following hierarchy applies: 2

• Mirtazapine 7.5-15 mg daily (most effective; SMD -1.20): Best efficacy and tolerability profile. 2, 4
• Vitamin B6 600-1200 mg daily (SMD -0.92): Excellent efficacy with superior tolerability. 2
• Biperiden 6 mg daily (SMD -1.01): Highly effective but anticholinergic burden limits use. 2
• Benzodiazepines (e.g., clonazepam): Provide symptomatic relief for anxiety component but do not address underlying mechanism. 1, 3, 5

Critical Clinical Considerations

Diagnostic Pitfalls

• Akathisia is frequently misinterpreted as psychotic agitation or anxiety, leading to inappropriate antipsychotic dose increases that worsen the condition. 3
• Systematically assess with validated scales (e.g., Barnes Akathisia Rating Scale) before starting antipsychotics and during dose titration. 6

Special Populations

• Children and adolescents have higher risk for extrapyramidal side effects and require careful monitoring. 3
• SSRI-induced akathisia is associated with increased suicidality, particularly with fluoxetine; systematically inquire about suicidal ideation before and after treatment initiation. 3

Medications to Avoid

• Anticholinergic agents are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed. 3, 6
• Avoid antipsychotic polypharmacy, which increases side effect burden without addressing akathisia. 3

Cardiovascular Considerations

• When switching antipsychotics in patients with high cardiovascular risk, carefully consider QT-prolonging effects. 3
• Monitor for orthostatic hypotension and bradycardia when using propranolol. 4

Evidence Quality Notes

The 2025 Lancet Psychiatry INTEGRATE guidelines provide the most current algorithmic approach, emphasizing dose reduction and switching as primary strategies. 1 The 2024 JAMA Network Open network meta-analysis represents the highest quality comparative evidence for adjunctive medications, demonstrating mirtazapine's superior efficacy over traditional propranolol. 2 However, propranolol remains guideline-recommended as first-line adjunctive therapy due to its established use and safety profile. 1, 3