Olanzapine as Alternative Therapy for Patients With Haloperidol-Induced Extrapyramidal Symptoms: Results of a Multicenter, Collaborative Trial in Latin America

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (-9.69 +/- 5.33; percentage change, 87.2%), the Barnes Akathisia Scale (-1.00 +/- 1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (-1.48 +/- 2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: -1.52 +/- 1.91-mg equivalents of benztropine; p <0.001). Significant mean baseline to endpoint improvements (p 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; -25.28 +/- 18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0-6 scale, -13.41 +/- 10.16; percentage change, 54.4%), and the Clinical Global Impressions Severity scale (-1.16 +/- 1.19; percentage change, 26.4%). Spontaneously reported treatment- emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.