What antipsychotic is least likely to cause akathisia?

Quetiapine Is Least Likely to Cause Akathisia Among Antipsychotics

Quetiapine is the antipsychotic medication least likely to cause akathisia based on current evidence, with sertindole being another option with negligible risk across examined doses. 1

Comparative Risk of Akathisia Among Antipsychotics

The risk of developing akathisia varies significantly between different antipsychotic medications:

• Lowest risk:

  • Quetiapine - carries negligible risk across all examined doses with a flat dose-response curve 1
  • Sertindole - also shows negligible risk across doses 1

• Moderate to high risk (in ascending order):

  • Iloperidone - estimated weighted incidence rate of 3.9% 2
  • Asenapine - estimated weighted incidence rate of 6.8% 2
  • Brexpiprazole - estimated weighted incidence rate of 10.0% 2
  • Lurasidone - estimated weighted incidence rate of 12.7% 2
  • Cariprazine - highest risk with estimated weighted incidence rate of 17.2% 2

Evidence Supporting Quetiapine's Lower Akathisia Risk

The 2025 Lancet Psychiatry guidelines specifically recommend quetiapine as a management option for akathisia: "Akathisia can potentially be managed with dose reduction. A switch to quetiapine or olanzapine can also be considered." 3

This recommendation is supported by systematic reviews and meta-analyses showing that quetiapine has a flat dose-response curve for akathisia risk, meaning the risk remains negligible even at higher doses 1.

Clinical Considerations When Using Quetiapine

Despite its favorable profile regarding akathisia, quetiapine is not entirely free from this side effect:

• Case reports exist of akathisia with quetiapine, particularly in patients predisposed to extrapyramidal symptoms 4, 5, 6
• FDA labeling data shows akathisia rates of 4% with quetiapine versus 1% with placebo in bipolar depression trials 7
• In adolescent schizophrenia trials, akathisia rates were 4.8% with quetiapine versus 4.0% with placebo 7

Important Monitoring and Management Strategies

When using any antipsychotic, including quetiapine:

1. Baseline assessment:

   • Document any pre-existing movement disorders
   • Assess risk factors for akathisia (previous history of EPS, young males, high doses)

2. Regular monitoring:

   • Use standardized scales like BARS (Barnes Akathisia Rating Scale) 8
   • Watch for both subjective (inner restlessness) and objective (excessive movements) components

3. If akathisia develops:

   • Consider dose reduction as first-line approach 3, 8
   • Adjunctive propranolol (10-30 mg two to three times daily) may be effective 3
   • For severe cases, switching to quetiapine or olanzapine is recommended 3

Special Considerations

• Anticholinergic burden: Quetiapine has relatively high central anticholinergic activity, which may contribute to its lower risk of EPS but can impact cognitive function 3

• Metabolic effects: While quetiapine has advantages regarding akathisia, it carries significant metabolic risks including weight gain, hyperglycemia, and hyperlipidemia 3

• Sedation: Quetiapine is highly sedating, which may be beneficial or problematic depending on the clinical scenario 7

• Elderly patients: Use lower doses due to increased sensitivity to CNS effects 8

Conclusion

When akathisia risk is the primary concern in antipsychotic selection, quetiapine represents the best choice among available options, with sertindole being another consideration with similarly low risk. However, the decision should balance this advantage against quetiapine's significant metabolic and sedative effects.