Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the Estimation of Early Drug Effect in First-Episode Psychosis: A Cross-sectional Assessment.

BACKGROUND: Studies on therapeutic drug monitoring (TDM) of second-generation antipsychotics (SGAs) have provided conflicting results regarding the association between dose, plasma concentrations, and drug effect and have focused rather on analyzing how individual drugs work. No study has attempted to process data from different SGAs globally to offer a panoramic view of the utility of TDM in clinical practice, and data on patients with first-episode psychosis (FEP) are lacking. This study aimed to assess the relationship between dose, plasma concentrations, and drug effect in a sample of patients with FEP, regardless of the SGA prescribed. METHODS: Data from 64 compliant patients treated with the same SGA during a 2-month follow-up were recorded. Clinical symptoms were assessed using the Positive and Negative Symptoms Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg für Kliniske Undersogelser scale. SGA doses were standardized to chlorpromazine equivalents, and patients were classified into 3 different ranges according to their plasma concentrations (subtherapeutic, therapeutic, and supratherapeutic). RESULTS: Plasma concentration ranges were proportionally related to dose. Patients with supratherapeutic plasma concentrations were treated with doses significantly higher than those with subtherapeutic concentrations. Dose and plasma concentrations were not associated with early drug effect. CONCLUSIONS: TDM seems unable to accurately estimate the early effects of SGAs in FEP. Ours is the first study to categorize plasma concentrations of SGAs into ranges for joint processing of data from a larger number of patients.

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.