From the Guidelines
Risperidone carries the highest risk of extrapyramidal side effects (EPSEs) among second-generation antipsychotics, particularly at higher doses, due to its relatively strong dopamine D2 receptor blockade 1. The risk of EPSEs with risperidone is dose-dependent, with significantly increased risk at doses above 4-6 mg per day. This occurs because risperidone has a relatively balanced serotonin-dopamine receptor binding profile compared to other SGAs, which typically have stronger serotonin 5-HT2A antagonism relative to D2 antagonism. Some key points to consider when prescribing risperidone include:
- Starting at lower doses (1-2 mg daily) and titrating slowly while monitoring for rigidity, tremor, bradykinesia, or akathisia.
- Being aware that paliperidone, the active metabolite of risperidone, shares a similar risk profile.
- Considering alternatives like quetiapine, olanzapine, or clozapine for patients particularly sensitive to movement disorders, as they carry lower EPSE risks 1. It's also important to note that anticholinergics should not be used routinely for preventing extrapyramidal side effects, and short-term use may be considered only in individuals with significant extrapyramidal side effects when dose reduction and switching strategies have proven ineffective, or when these side effects are acute or severe 1.
From the Research
Second Generation Antipsychotic with the Highest EPSE Risk
- Risperidone is associated with a higher risk of Extrapyramidal Symptoms (EPS) compared to other second-generation antipsychotics such as paliperidone, aripiprazole, and olanzapine 2.
- Studies have shown that risperidone has a higher incidence of EPS, including parkinsonism, dystonia, and dyskinesia, compared to other atypical antipsychotics 3, 4.
- However, it's worth noting that the risk of EPS with risperidone is still lower than that of first-generation antipsychotics such as haloperidol 5, 4.
- A comparison of second-generation antipsychotics found that olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine, but less than risperidone 6.
Comparison of EPS Risk among Second-Generation Antipsychotics
- Risperidone: higher risk of EPS compared to paliperidone, aripiprazole, and olanzapine 2, 3, 4.
- Olanzapine: may be associated with slightly more extrapyramidal side effects than quetiapine, but less than risperidone 6.
- Quetiapine: may have a lower risk of EPS compared to olanzapine and risperidone 6.
- Aripiprazole: may have a lower risk of EPS compared to risperidone 2, 6.