Treatment of Akathisia
The first-line treatment for akathisia is to reduce the antipsychotic dose or switch to a lower-risk agent (quetiapine or olanzapine), combined with propranolol 10-30 mg two to three times daily as the most consistently effective pharmacological intervention. 1, 2
Critical Initial Recognition
A major pitfall is misinterpreting akathisia as psychotic agitation or anxiety, which leads clinicians to inappropriately increase antipsychotic doses and worsen the condition. 1, 2 This misdiagnosis must be actively avoided through systematic assessment with validated scales before starting antipsychotics and during dose titration. 3
First-Line Treatment Algorithm
Step 1: Antipsychotic Modification
- 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
- In patients with high cardiovascular risk, carefully consider QT-prolonging effects when switching medications. 1, 2
Step 2: Add Propranolol
- Propranolol (10-30 mg two to three times daily) is the most consistently effective treatment for akathisia and should be initiated simultaneously with dose reduction. 1, 2, 4, 5, 6
- Propranolol has the strongest evidence base among all pharmacological interventions, though clinicians should be aware of contraindications including asthma, orthostatic hypotension risk, and bradycardia. 4
Second-Line Options (When First-Line Fails)
Benzodiazepines
- Clonazepam provides symptomatic relief and addresses the anxiety component of akathisia in patients who do not respond to first-line treatments. 1, 6
- Benzodiazepines are a sensible next choice, especially if subjective distress persists despite beta-blocker therapy. 5
5-HT2A Antagonists
- Low-dose mirtazapine (7.5 mg or 15 mg once daily) has the most compelling evidence among serotonin 5-HT2A antagonists for therapeutic efficacy. 4, 6
- Other 5-HT2A antagonists (trazodone, mianserin) have shown promise but with less robust evidence. 4, 7
Third-Line and Alternative Options
Anticholinergic Agents
- Anticholinergics are 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 tried, with dosing individualized to patient need. 8
- Monitor carefully for anticholinergic side effects, particularly in children and adolescents. 1
Other Agents
- Amantadine is considered a fourth-line option with limited evidence. 1
- Clonidine can be attempted if beta-blockers, benzodiazepines, and 5-HT2A antagonists are unsuccessful. 5, 6
Special Population Considerations
Children and Adolescents
- Children and adolescents are at higher risk for extrapyramidal side effects including akathisia compared to adults and require careful monitoring. 1, 2
SSRI-Induced Akathisia
- SSRI-induced akathisia is associated with increased suicidality, particularly with fluoxetine. 1, 2
- Systematically inquire about suicidal ideation before and after treatment initiation when akathisia occurs with antidepressant therapy. 1, 2
- Be especially alert to the possibility of suicidality if SSRI treatment is associated with onset of akathisia. 1
Acute Dystonic Reactions
- For acute presentations, 1-2 mL of benztropine injection usually relieves the condition quickly, followed by tablets 1-2 mg twice daily to prevent recurrence. 8
- In emergency settings, intramuscular administration is preferred over intravenous route. 1
Duration of Treatment
When extrapyramidal disorders develop soon after initiation of neuroleptic drugs, they are likely to be transient. 8 After one or two weeks of treatment with adjuvant medications, the drug should be withdrawn to determine continued need. 8 If disorders recur, treatment can be reinstituted. 8