EXTRAPYRAMIDAL SYMPTOMS AND TOLERABILITY OF OLANZAPINE VERSUS HALOPERIDOL IN THE ACUTE TREATMENT OF SCHIZOPHRENIA

Background: A relative lack of extrapyramidal symptoms (EPS, i.e., the syndromes of dystonia, parkinsonism, akathisia, dyskinesia) is one cr iterion used to determine whether an antipsychotic is ''atypical.'' Th e extrapyramidal symptom profiles of the novel antipsychotic olanzapin e and the conventional antipsychotic haloperidol were compared in a po pulation of 2606 patients from three well-controlled prospective clini cal trials. Method: Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine (5 to 20 mg/day) and 810 patients tr eated with haloperidol (5 to 20 mg/day) for up to 6 weeks of therapy. Patients were monitored weekly by three methods of extrapyramidal symp tom assessment: (1) detection of extrapyramidal adverse events (signs and symptoms) by casual observation, nonprobing inquiry, and spontaneo us report; (2) objective rating scale scores; and (3) use of concomita nt anticholinergic medications. Emergence of EPS was assessed by (1) a nalysis of the incidence of extrapyramidal syndrome categories based o n adverse events, (2) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores, (3) analysis of mean m aximum change in rating scale scores, and (4) categorical analysis of anticholinergic medication use. Outcome of EPS was assessed by (1) ana lysis of mean change in rating scale scores at endpoint and (2) mean a nticholinergic use at endpoint. Results: Olanzapine was statistically significantly (p = .014, p < .001) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome. Furthermore, during acute treatment, statistically signifi cantly fewer patients treated with olanzapine (0.3%) discontinued the study because of any extrapyramidal adverse event than patients treate d with haloperidol (2.7%, p < .001). Conclusion: Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile tha n the conventional antipsychotic haloperidol at comparably effective a ntipsychotic doses. The lower extrapyramidal symptom profile with olan zapine was evident despite statistically significantly more frequent u se of anticholinergic drugs among haloperidol-treated patients. Fewer olanzapine-treated than haloperidol-treated patients discontinued beca use of EPS, suggesting that olanzapine should contribute to better com pliance with longer term maintenance treatment, with minimal anticholi nergic-associated events.