A naturalistic study of high-dose clozapine treatment in refractory schizophrenia using a within-subject design

Abstract

Objective : Clozapine is the treatment of choice for treatment-resistant schizophrenia. However, some patients with clozapine treatment at the typical recommended dosage (300-600 mg/day) continue to experience significant symptoms. This naturalistic follow-up study evaluated the efficacy and safety of clozapine at a higher than typical dose in patients with refractory schizophrenia.

Methods : Thirteen of 19 subjects with refractory schizophrenia completed this prospective, open-label trial. The primary efficacy measure was the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), and safety measures included the Simpson Angus Rating Scale (SAS) and recording of adverse events. Repeated measures ANOVA was used to evaluate whether a higher dose of clozapine resulted in further symptom improvement.

Results : No improvement was found in overall psychopathology, except for PANSS general psychopathology scores, when going from 600 mg/day to the higher dose of clozapine, although the higher dose was well tolerated.

Conclusion : This open study suggests that clozapine at a higher dosage does not improve overall symptoms more than 600 mg/day, although has comparable tolerability. Augmentation or determination of other possible factors related to refractoriness should be considered to improve symptoms in cases in which typical dosage clozapine does not fully elicit a response. The results of this study must be confirmed with a larger sample size and controlled trials in the near future.