Relating Spontaneously Reported Extrapyramidal Adverse Events to Movement Disorder Rating Scales

Background: While antipsychotic-induced extrapyramidal symptoms (EPS) and akathisia remain important concerns in the treatment of patients with schizophrenia, the relationship between movement disorder rating scales and spontaneously reported EPS-related adverse events (EPS-AEs) remains unexplored. Methods: Data from four randomized, placebo- and haloperidol-controlled ziprasidone trials were analyzed to examine the relationship between spontaneously reported EPS-AEs with the Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Categorical summaries were created for each treatment group to show the frequencies of subjects with EPS-AEs in each of the SAS and BARS categories at weeks 1, 3, and 6, and agreement between ratings was quantified by means of weighted kappa (κ). Results: In general, we found greater frequencies of EPS-AEs with increasing severity of the SAS and BARS scores. The EPS-AEs reported with a “none” SAS score ranged from 0 to 22.2%, with a “mild” SAS score from 3.3 to 29.0%, and with a “moderate” SAS score from 0 to 100%. No subjects in any treatment group reported “severe” SAS scores or corresponding EPS-AEs. Agreement between SAS scores and EPS-AEs was poor for ziprasidone and placebo (κ < 0.2) and only slightly better for haloperidol. The EPS-AEs reported with “non questionable” BARS scores ranged from 1.9 to 9.8%, with “mild moderate” BARS scores from 12.8 to 54.6%, and with “marked severe” scores from 0 to 100%. Agreement was modest for ziprasidone and placebo (κ < 0.4) and moderate for haloperidol (κ < 0.6). Conclusions: These findings may reflect either underreporting of AEs by investigators and subjects or erroneous rating scale evaluations.