Correlates of Clozapine Use after a First Episode of Schizophrenia: Results From a Long-term Prospective Study.

Abstract

Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia. To identify variables that predict clozapine use after a first episode of schizophrenia (FES). Patients with FES and ≤15days of lifetime antipsychotic treatment were followed up during naturalistic treatment, and the patients who were initiated on clozapine were compared with those receiving non-clozapine antipsychotics for ≥24months regarding demographic and clinical baseline characteristics, adherence, and relapse patterns during follow-up. Treatment-resistant schizophrenia was defined as two or more antipsychotic trials of adequate dose for ≥6weeks. Twenty-eight patients who used clozapine and 77 non-clozapine antipsychotic users were included. Clozapine was initiated after a mean of 2.5±1.1 adequate antipsychotic trials. Eight of the 28 clozapine-treated patients (28.6%) began their clozapine treatment during the first 12months of follow-up (mean 7.1±3.3months) and their premorbid childhood adjustment was significantly worse than those who started clozapine later (mean 78.5±43.0months). Compared with non-clozapine users, patients who started clozapine had significantly more relapses in the first 6months of follow-up prior to clozapine use (35.7 vs. 11.7%, p=0.005), and were significantly more likely to have a first relapse despite treatment adherence (38.1 vs. 73.3%, p=0.01). In the multivariate analyses, antipsychotic polypharmacy and first relapse despite adherence to antipsychotic treatment independently predicted subsequent clozapine use. Clozapine use after a FES was predicted by a first relapse while being adherent to non-clozapine antipsychotics, especially if the first relapse occurred within the first 6months. Developmental childhood difficulties predicted significantly earlier clozapine use.