Rates of complete nonadherence among atypical antipsychotic drugs: A study using blood samples from 13,217 outpatients with psychotic disorders.

Background: Nonadherence to antipsychotics may cause relapse and hospitalizations in patients with psychotic disorders. The purpose was to quantify and compare the outpatient's nonadherence rates of atypical antipsychotics by objective detection in blood samples.

Methods: Totally, 13,217 outpatients with therapeutic drug monitoring (TDM) data of atypical antipsychotics were included. An event of complete nonadherence was defined as an occurrence of undetectable level of a prescribed antipsychotic in the blood sample submitted for TDM. Patients with such an event(s) were defined as nonadherent of the respective drug treatment (outcome). The rates of nonadherence patients were compared between the drugs by logistic regression.

Results: In the study population, 70.2% of the patients were prescribed doses compliant with a schizophrenia diagnosis. The mean olanzapine equivalent dose in the population was 13.4 mg (95% confidence interval (CI): 13.3, 13.6). The frequency of nonadherence patients, regardless of drug, was 3.7% (CI: 3.4-4.0). The nonadherence patient rate was lowest in clozapine-treated patients (2.2%; CI: 1.5-2.8), followed by aripiprazole (2.3%; 1.7-2.8), risperidone (2.4%; 1.6-3.0), quetiapine (2.8%; 2.3-3.2) and olanzapine (4.9%; 4.1-5.3). Users of olanzapine had significantly higher risk of complete nonadherence (Odds ratio: 1.9; CI: 1.6-2.3, p < 0.001) compared to patients treated with other antipsychotics as a group.

Conclusions: In this study, complete nonadherence of atypical antipsychotics, measured as undetectable blood level, was disclosed for ~5% of outpatients with psychotic disorders. The rate of complete nonadherence was significantly higher during olanzapine treatment compared to other atypical antipsychotics. Further studies should investigate if this reflects drug differences in tolerability or other causal relationships.