Association between previous and future antipsychotic adherence in patients initiating clozapine: real-world observational study

Br J Psychiatry. 2022 Jan 27:1-8. doi: 10.1192/bjp.2022.1. Online ahead of print.


Background: Although recognised as the most effective antipsychotic for treatment-resistant schizophrenia, clozapine remains underused. One reason is the widespread concern about non-adherence to clozapine because of poor adherence before initiating clozapine.

Aims: To determine if prior poor out-patient adherence to treatmentbefore initiating clozapine predisposes to poor out-patient adherence to clozapine or to any antipsychotics (including clozapine) after its initiation.

Method: This cohort study included 3228 patients with schizophrenia living in Quebec (Canada) initiating (with a 2-year clearance period) oral clozapine (index date) between 2009 and 2016. Using pharmacy data, out-patient adherence to treatment was measured by the medication possession ratio (MPR), over a 1-year period preceding and following the index date. Five groups of patients were formed based on their prior MPR level (independent variable). Two dependent variables were defined after clozapine initiation (good out-patient adherence to any antipsychotics and to clozapine only). Along with multiple logistic regressions, state sequence analysis was used as a visual representation of antipsychotic-use trajectories over time, before and after clozapine initiation.

Results: Although prior poor adherence to antipsychotics was associated with poor adherence after clozapine initiation, the absolute risk of subsequent poor adherence remained low, regardless of previous adherence level. Most patients adhered to their treatment after initiating clozapine (>68% to clozapine and >84% to any antipsychotics).

Conclusions: Despite the fact that poor adherence prior to initiating clozapine is widely recognised by clinicians as a barrier for the prescription of clozapine, the current study supports the initiation of clozapine in all eligible patients.

Keywords: Antipsychotic; clozapine; observational studies; schizophrenia; state sequence analysis.