Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: An open-label, prospective trial

The role of olanzapine in treatment-resistant schizophrenia is still unreso lved. This article presents an open-label, prospective, 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder sele cted for unambiguous resistance to either clozapine or risperidone and to t ypical antipsychotics. Forty-three inpatients (mean age, 41.6 years; mean d uration of illness, 21.7 years) were enrolled and treated after cross-titra tion from their previous antipsychotic treatment with olanzapine 10 to 40 m g daily without any concomitant antipsychotic medication. Patients were eva luated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale, and the Extrapyramidal Symptom Rating Scale. The change with olanzapine treatment was associated with a PANSS total score im provement of 3.7 (SD = 15.6; not significant). There was a significant impr ovement for the PANSS cognitive and depression/anxiety factors, whereas the PANSS excitement factor worsened. The improvement rate was superior in pat ients receiving olanzapine doses higher than 20 mg. A total of 16.7% of pat ients reached response criteria set forth by a previous study. There was a significant decrease in extrapyramidal side effects (t = 2.04; p < 0.05) an d statistically significant, yet modest, weight gain. These results indicat e that olanzapine is only modestly effective in these severely treatment-re sistant patients with schizophrenia. However, a trial with olanzapine can b e recommended in these patients before moving to augmentation strategies, g iven the lack of proven alternatives and the observation that 16.7% of pati ents reached the response criteria.