Pharmacological treatment of schizophrenia resistant to first-line treatment: a critical systematic review and meta-analysis

Abstract

Schizophrenia resistance to conventional antipsychotics is a common phenomenon. In 5-25% of cases, satisfactory treatment response is not achieved, and intolerance to conventional antipsychotics occurs in 5-20% of patients. Numerous reasons for refractoriness have been proposed. However, up to now only a few pharmacological agents have been found useful in the treatment of schizophrenia resistant to conventional antipsychotics. This paper critically reviews quality-assessed trials on the pharmacological treatment of refractory schizophrenia. Randomized blinded trials of conventional antipsychotics at high doses, atypical antipsychotics, lithium, propranolol, and agents not traditionally used in the treatment of schizophrenia are reviewed. On the basis of the methodologically sound studies included, we conclude that only clozapine has proved to be clinically effective in the treatment of refractory schizophrenia. In the short term, the odds ratio for clinical improvement on clozapine treatment when compared to conventional treatment is calculated to be 2.4 (95% confidence interval [CI] 1.7-3.5) and the number of patients needed to treat (NNT) is 7 (95% CI 5-13). In single inconclusive trials, olanzapine and risperidone have been found as effective as clozapine. In order to establish the usefulness of other pharmacological treatments, more randomized clinical trials are needed.

Keywords: atypical antipsychotics; clinical trials; clozapine; conventional antipsychotics; schizophrenia treatment resistance.