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

Background: Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia.

Objectives: To identify variables that predict clozapine use after a first episode of schizophrenia (FES).

Methods: Patients with FES and ≤15 days 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 ≥24 months 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 ≥6 weeks.

Results: 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 12 months of follow-up (mean 7.1 ± 3.3 months) and their premorbid childhood adjustment was significantly worse than those who started clozapine later (mean 78.5 ± 43.0 months). Compared with non-clozapine users, patients who started clozapine had significantly more relapses in the first 6 months 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.

Conclusions: 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 6 months. Developmental childhood difficulties predicted significantly earlier clozapine use.