Clozapine for severe (“kraepelinian”) schizophrenia: Sustained improvement over 5 years

Clozapine has become a keystone in the treatment of schizophrenia because of its efficacy as an antipsychotic with negligible neuroleptic effects. The long-term stability of its effects, however, is poorly understood, because most studies have probed the usefulness of clozapine over a period of weeks to several months at the most. Knowing whether clozapine's benefits are sustained over the very long-term, i.e., more than 5 years, may be critical for cost-benefit analyses. Objective To report the results of an open study on the efficacy of clozapine over the very long-term. Methods Thirty-three adults (26 men) with severe (kraepelinian) schizophrenia were assessed at regular intervals using a brief neuropsychiatric battery over a 5-year period. Results A significant improvement was observed between the pre-clozapine and the first "on-clozapine" evaluation. This improvement was paralleled by a remarkable conversion of schizophrenia from "active" (mostly paranoid) into "residual" in 70% of all patients. Eight patients became functionally productive to the point of being capable of living an independent life. Roughly one-third of our cases showed no improvement. Conclusions Clozapine is a safe and effective drug for patients with severe schizophrenia who have failed to improve on other antipsychotic drugs. Clozapine's maximal benefit is established by the end of the first year of treatment and continues unabated for many years thereafter. Clozapine-resistant patients remain a major challenge calling for the discovery of new treatments for schizophrenia.