Sertindole is an antipsychotic agent that shows affinity for D2, 5-HT2A, 5-HT2C, and a1-adrenoceptors. Preclinical research suggests that sertindole has a preferential effect on the activity of limbic and cortical dopaminergic neurons, and clinical trials have confirmed that sertindole is efficacious at a low D2 receptor occupancy, comparable to that produced by clozapine, which may confer a lower risk of EPS.

PubMED was searched for all randomised controlled trials of sertindole where EPS ratings were performed and published in English language in peer-reviewed medical journals. All of these published studies were reviewed regarding the occurrence of EPS in patients.

Five clinical trials of sertindole fulfilled these criteria. Comparators were placebo, haloperidol and risperidone. Rating scales used were: Simpson –Angus Scale (SAS), Barnes Akathisia Scale (BAS), and Abnormal Involuntary Movement Scale (AIMS). Furthermore, the need for anti EPS medication, and the incidence of EPS-related events (presented as percentage of patients), if registered, was recorded. If significant differences were reported, NNT (number needed to treat) values were calculated and presented with point estimates and 95% CI. In three studies significant differences between sertindole and haloperidol were observed. In the two remaining studies, no significant differences were noted between sertindole vs placebo and risperidone, respectively.

In summary sertindole has been shown to have an exceptionally low propensity for EPS, and abnormal movement side effects.