What is the best approach to treat akathisia in a patient, potentially caused by antipsychotic medications?

Treatment of Akathisia

For antipsychotic-induced akathisia, first reduce the antipsychotic dose if clinically feasible, or switch to quetiapine or olanzapine; if medication adjustment is not possible, add propranolol 10-30 mg two to three times daily as the most effective pharmacological treatment. 1, 2

Immediate First-Line Management

The treatment hierarchy is clear and should be followed sequentially:

Step 1: Medication Adjustment (Preferred)

• Lower the current antipsychotic dose while remaining within the therapeutic range—this directly addresses the cause and is dose-dependent 1, 2
• Switch to an antipsychotic with lower akathisia risk, specifically quetiapine or olanzapine, which have the lowest propensity for causing akathisia 1, 2, 3
• Use gradual cross-titration to avoid withdrawal phenomena 3

Step 2: Pharmacological Treatment (When Dose Adjustment Not Feasible)

• Propranolol 10-30 mg two to three times daily is the most consistently effective and evidence-based treatment for acute akathisia 1, 2, 4, 5, 6
• This is a lipophilic beta-blocker that has demonstrated superior efficacy compared to other agents 4

Second-Line Options

If propranolol fails, is contraindicated (asthma, bradycardia, orthostatic hypotension), or is poorly tolerated 6:

• Benzodiazepines (clonazepam or lorazepam) provide symptomatic relief, particularly for the subjective distress and anxiety component 1, 2, 4, 5
• Low-dose mirtazapine (7.5-15 mg once daily) has compelling evidence as a serotonin 5-HT2a antagonist with anti-akathisia properties 5, 6, 7

Third-Line and Alternative Agents

When first- and second-line treatments are unsuccessful:

• Amantadine (mild dopaminergic agent) can be tried, though evidence is limited 2, 4
• Clonidine may be effective in some cases 4, 5
• Gabapentin or pregabalin (voltage-gated calcium channel blockers) have shown promise 7

What NOT to Do: Critical Pitfalls

• Do not use anticholinergic agents (benztropine, trihexyphenidyl) as first-line treatment—they are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed 1, 2, 8
• Do not mistake akathisia for psychotic agitation or anxiety, which leads to inappropriate antipsychotic dose escalation and worsens the condition 1, 2, 3
• Do not abruptly discontinue the antipsychotic, as withdrawal akathisia can occur 3
• Avoid antipsychotic polypharmacy, which increases side effect burden without addressing the underlying problem 1, 2

Special Monitoring Considerations

• SSRI-induced akathisia (particularly fluoxetine) is associated with increased suicidality—systematically inquire about suicidal ideation before and after treatment initiation 1, 2
• Children and adolescents are at higher risk for extrapyramidal side effects including akathisia and require careful monitoring 2
• Use standardized akathisia severity scales during treatment transitions to objectively track response 3

Practical Treatment Algorithm

1. Assess severity and impact on patient function and distress
2. If possible: Reduce antipsychotic dose OR switch to quetiapine/olanzapine 1, 2, 3
3. If medication change not feasible: Start propranolol 10-30 mg two to three times daily 1, 2, 4, 5
4. If propranolol fails or contraindicated: Add benzodiazepine (clonazepam/lorazepam) OR try low-dose mirtazapine 7.5-15 mg daily 2, 5, 6
5. If still refractory: Consider amantadine, clonidine, or gabapentin 4, 5, 7
6. Rotate between strategies if chronic akathisia proves resistant to single-agent therapy 7

The evidence strongly supports propranolol as the gold standard when antipsychotic adjustment is not possible, with mirtazapine emerging as a compelling alternative based on recent research 5, 6. Anticholinergics should be reserved for dystonia or parkinsonism, not akathisia 1, 2.