A Pilot Study of the Usefulness of a Single Olanzapine Plasma Concentration as an Indicator of Early Drug Effect in a Small Sample of First-Episode Psychosis Patients

PURPOSE/BACKGROUND: Studies analyzing concentration-effect relationships in second-generation antipsychotics have reported contradictory results in chronic schizophrenia. No data are available for the early stages of the disease. The present study aims to evaluate the association between a single olanzapine plasma concentration, clinical response, and severity of adverse effects in first-episode psychosis (FEP); to test the utility of various plasma breakpoints as markers of early response to treatment; and to identify variables affecting olanzapine concentrations. METHODS: Data from 23 compliant FEP patients receiving olanzapine monotherapy (5–30 mg/d) were evaluated 2 months after beginning treatment. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg for Kliniske Undersøgelser scale. Plasma samples were drawn at 11 (SD, 1) hours after dosing and analyzed with high-performance liquid chromatography/tandem mass spectrometry. FINDINGS: Consistent with findings on chronic disease, dose, age, sex, weight, and cigarettes/day accounted for some of the variability in olanzapine concentrations. While no relationship was found between olanzapine concentrations and adverse effects or improvement of depressive symptoms, response of psychotic symptoms was associated with concentrations between 22.56 and 77.92 ng/mL. Plasma breakpoints did not show sufficiently high specificity, resulting in a large number of false-positive results. IMPLICATIONS: Although olanzapine concentrations do not seem to be reliable indicators of early drug effect in FEP, they may still prove useful for detecting noncompliance, as well as pharmacokinetically relevant comorbidities or genetic particularities in drug metabolism.