What is akathisia and how is it treated?

Akathisia: Definition and Treatment

Akathisia is a distressing neuropsychiatric syndrome characterized by subjective feelings of inner restlessness and an urge to move, with objective components including rocking while standing/sitting, lifting feet as if marching, and crossing/uncrossing legs. The first-line treatment is propranolol 10-30mg two to three times daily, or alternatively, dose reduction of the causative medication. 1

What is Akathisia?

Akathisia consists of both subjective and objective components:

• Subjective components:

  • Inner restlessness
  • Intense urge to move
  • Significant distress

• Objective components:

  • Rocking while standing or sitting
  • Lifting feet as if marching on the spot
  • Crossing and uncrossing legs while sitting
  • Inability to sit still

Akathisia is most commonly caused by antipsychotic medications but can occur with other medications as well. It can be classified according to time of onset as acute, tardive, withdrawal, or chronic akathisia 2. Reported prevalence rates vary widely between 5% and 36.8% among patients taking antipsychotics 2.

Treatment Algorithm

First-line approaches:

1. Address the causative medication:

   • Lower the dosage of the causative antipsychotic medication 1
   • Switch to another antipsychotic with lower akathisia risk (second-generation/atypical antipsychotics generally have lower risk) 1

2. Pharmacological interventions:

   • Beta-blockers: Propranolol 10-30mg two to three times daily (most consistently effective treatment) 1, 2
     • Caution: Use carefully in patients with asthma, diabetes, or cardiovascular disease

Second-line approaches:

1. Benzodiazepines: Lorazepam 0.5-2mg as needed 1

   • Caution: Regular use can lead to tolerance and dependence
   • Watch for paradoxical agitation, which occurs in about 10% of patients

2. Consider switching to antipsychotics with lower akathisia risk:

   • Quetiapine (initial dose: 12.5mg twice daily; maximum: 200mg twice daily) 1
   • Iloperidone (has the lowest akathisia incidence rate at 3.9% compared to other newer antipsychotics) 3

Third-line approaches (when first and second-line treatments fail):

1. Amantadine or clonidine 2

2. Serotonin 5-HT2a receptor antagonists:

   • Mirtazapine (7.5mg or 15mg once daily) has shown compelling evidence for efficacy 4
   • Other options include ritanserin, cyproheptadine, trazodone, and mianserin 4

Monitoring and Assessment

• Use standardized scales like AIMS (Abnormal Involuntary Movement Scale) for regular assessment 1
• Monitor for orthostatic hypotension in patients with cardiovascular disease when using beta-blockers 1
• Watch for QT prolongation and rare cases of cardiomyopathy with quetiapine 1

Special Considerations

• Elderly patients: Use lower doses of medications due to increased sensitivity to CNS effects 1
• Parkinson's disease patients: Extremely sensitive to antipsychotic effects; consider pimavanserin, clozapine, or quetiapine 1
• Severity impact: Akathisia can significantly impact treatment adherence and quality of life, potentially leading to treatment discontinuation 3
• Differential diagnosis: Akathisia can be misinterpreted as anxiety, agitation, or psychotic agitation, leading to inappropriate dose increases that worsen the condition 5

Clinical Pearls

• Akathisia with newer antipsychotics (NAPs) is generally mild to moderate, leading to treatment discontinuation in less than 5% of cases 3
• The use of a newer antipsychotic raises the akathisia risk more than two-fold compared to placebo 3
• Among newer antipsychotics, iloperidone has the most benign akathisia profile, while cariprazine has the highest risk 3
• Prevention is optimal management - standardized titration and use of novel antipsychotics with lower risk profiles are successful preventive measures 2