Is risperidone (Risperdal) more likely to induce akathisia?

Risperidone is More Likely to Induce Akathisia Than Many Other Antipsychotics

Yes, risperidone is more likely to induce akathisia compared to several other atypical antipsychotics, particularly clozapine, iloperidone, and asenapine. Among the atypical antipsychotics, risperidone has a higher propensity for causing extrapyramidal symptoms, including akathisia.

Evidence for Risperidone's Higher Risk of Akathisia

• Of the atypical antipsychotics, risperidone appears to be the most likely to produce extrapyramidal side effects, including akathisia 1
• In comparative studies, the point-prevalence of akathisia was 7.3% in patients treated with clozapine, 13% in those treated with risperidone, and 23.8% in those treated with conventional antipsychotics 2
• A 2019 meta-analysis of newly approved antipsychotics found significant differences in akathisia rates, with iloperidone (3.9%) and asenapine (6.8%) showing significantly lower rates than risperidone, which typically shows rates of 10-15% 3

Mechanism and Clinical Presentation

• Akathisia is characterized by a subjective feeling of inner restlessness along with objective evidence of motoric restlessness 4
• Risperidone's higher propensity for causing akathisia is likely related to its significant D2 receptor antagonism combined with alpha-1 and alpha-2 noradrenergic antagonism 1
• Akathisia can manifest as both acute and tardive forms, with tardive akathisia being a rarer but more challenging to manage complication 4

Comparative Risk Among Antipsychotics

• The FDA drug label for risperidone reports akathisia rates of 9-10% in adult schizophrenia patients and 9-10% in bipolar patients 5
• In pediatric patients with schizophrenia, akathisia rates with risperidone were reported as 9-10%, significantly higher than placebo 5
• A systematic review found the estimated odds ratio for akathisia compared to placebo was lowest for iloperidone (OR 1.20) and increased for brexpiprazole (OR 2.04), asenapine (OR 2.37), lurasidone (OR 3.74), and cariprazine (OR 4.35) 3

Clinical Implications and Management

• Due to risperidone's side effect profile, including akathisia, it should be considered only after assessing whether potential contributors to symptoms could be addressed by non-pharmacological means 1
• Akathisia can negatively impact clinical outcomes and may lead to treatment discontinuation in some cases 3
• Risperidone-induced akathisia may be confused with restless legs syndrome, as they share some clinical features, requiring careful differential diagnosis 6
• In neuroleptic-naïve patients, the incidence of akathisia with risperidone is comparable to that of low-dose haloperidol, suggesting it may not offer advantages in this specific population 7

Special Populations

• In children and adolescents with intellectual disability/developmental disorder, risperidone has shown efficacy for irritability and aggression but carries significant risk of side effects including akathisia 1
• For treatment of ADHD symptoms in children with intellectual disability, despite risperidone showing efficacy, methylphenidate remains the first-line agent due to risperidone's side effect profile, including akathisia 1

Monitoring and Prevention

• Regular assessment for akathisia using standardized scales like the Barnes Akathisia Scale is recommended when initiating risperidone 2
• The severity of akathisia with atypical antipsychotics is generally mild to moderate, but can still lead to treatment discontinuation in some cases (though less than 5%) 3
• Consider lower starting doses and slower titration of risperidone to minimize the risk of akathisia, particularly in antipsychotic-naïve patients 7