A qualitative assessment of the neurological safety of antipsychotic drugs; an analysis of a risperidone database

Abstract

Background: Neurological side effects of antipsychotic agents limit the use of these drugs, and development of newer antipsychotic agents has been focused on a reduced risk of extrapyramidal symptoms (EPS) as well as effective symptom control.

Methods: A qualitative analysis of EPS was performed using Extrapyramidal Symptom Rating Scale (ESRS) data from 11 double-blind risperidone trials. An ESRS factor analysis and maximum changes in ESRS scores were compared for the risperidone, haloperidol, and placebo groups.

Results: The factor analysis revealed five factors. Between-group comparisons showed no differences between placebo and 1 to 2 mg/day-risperidone groups. Parkinsonism, tremor, akathisia, and sialorrhea were more likely to occur with haloperidol than with placebo or risperidone at 1 to 6 mg/day. Similar results were noted by maximum changes in ESRS scores. At risperidone doses of more than 8 mg/day, acute EPS severity lay between that of the placebo and haloperidol groups. The severity of tardive dyskinesia was greater in patients receiving placebo than in those receiving either active treatment.

Conclusions: As the results described above were derived from a post hoc analysis of an existing database, conclusions must remain tentative. To provide more definitive answers, EPS assessments in future studies should be refined to more accurately predict the type of EPS expected with a given agent in clinical practice.