How to manage akathisia caused by antipsychotic medications?

Management of Akathisia Caused by Antipsychotic Medications

The first-line treatment for antipsychotic-induced akathisia is to lower the antipsychotic dose (if within therapeutic range), switch to a lower-risk antipsychotic like quetiapine or olanzapine, or add propranolol 10-30 mg two to three times daily. 1

Initial Assessment and Recognition

• Akathisia presents as both subjective inner restlessness with an urge to move and objective signs including pacing, rocking while standing or sitting, lifting feet as if marching, and crossing/uncrossing legs 2
• This condition is frequently misinterpreted as psychotic agitation or anxiety, which can lead to inappropriate increases in antipsychotic dosage that worsen the condition 1
• Acute akathisia typically occurs early in treatment, within the first few days to weeks after starting antipsychotic medication or increasing the dose 3

First-Line Treatment Algorithm

Step 1: Dose Reduction or Medication Switch

• Reduce the current antipsychotic dosage while remaining within therapeutic range 1
• If dose reduction is insufficient, switch to an antipsychotic with lower akathisia risk such as quetiapine or olanzapine 1
• Avoid antipsychotic polypharmacy as this increases side effect burden 1

Step 2: Add Propranolol

• Propranolol is the most consistently effective pharmacological treatment for akathisia 1, 2
• Dose: 10-30 mg two to three times daily 1
• Propranolol and other lipophilic beta-blockers show the strongest evidence for efficacy 2
• Consider contraindications including asthma, bradycardia, and orthostatic hypotension 4

Second-Line Options When Beta-Blockers Fail

Benzodiazepines

• Add benzodiazepines such as clonazepam if first-line treatments are ineffective 1
• These provide symptomatic relief and address the anxiety component of akathisia 1
• Particularly useful if subjective distress persists despite other interventions 2

Serotonin 5-HT2a Antagonists

• Low-dose mirtazapine (7.5-15 mg once daily) has demonstrated compelling evidence for therapeutic efficacy 4
• Other agents with 5-HT2a antagonism (trazodone, cyproheptadine) may be considered 4
• This represents an emerging class of anti-akathisia agents with better tolerability profiles 4

Third and Fourth-Line Options

• Amantadine is considered a fourth-line option with limited evidence 1
• Clonidine can be tried if beta-blockers and benzodiazepines are unsuccessful 2
• Anticholinergic agents are notably less effective for akathisia compared to other extrapyramidal side effects, despite being commonly prescribed 1

Critical Warnings and Special Considerations

SSRI-Induced Akathisia

• SSRI-induced akathisia is associated with increased suicidality, particularly with fluoxetine 1
• Systematically inquire about suicidal ideation before and after treatment initiation 1
• Be especially alert to suicidality if SSRI treatment is associated with onset of akathisia 1

Withdrawal Akathisia

• Akathisia can develop when tapering antipsychotics, particularly amisulpride 5
• Slow tapering and careful monitoring are recommended when switching antipsychotics 5
• Switching to aripiprazole with propranolol may be effective for withdrawal akathisia 5

Cardiovascular Considerations

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

Common Pitfalls to Avoid

• Do not increase the antipsychotic dose when akathisia is mistaken for worsening psychosis or agitation 1
• Do not rely solely on anticholinergic agents as they are less effective for akathisia than for other extrapyramidal symptoms 1
• Do not abruptly discontinue or rapidly taper antipsychotics, as this can precipitate withdrawal akathisia 5
• Do not add another dopamine-blocking agent if tardive dyskinesia is also present, as this will worsen the condition 3