Plasma olanzapine concentration: Relation with dose, adherence to medication, and clinical efficacy

Abstract

Objective: To estimate plasma olanzapine concentration (POC) using liquid chromatography-mass spectrometry (LCMS) and identify factors that contributes to pharmacokinetic variability of olanzapine. Materials and Methods: This was a prospective, observational study initiated after approval of institutional ethics committee. Stable patients of schizophrenia on olanzapine, above 18 years of age, of either gender, on olanzapine therapy for at least 12 weeks with no change in dose for at least one week were included. Plasma levels of olanzapine were assessed using HPLC based kit on LCMS. To assess response to treatment patients were subjected to Brief Psychiatric Rating Scale (BPRS) in which lower score indicates better response. Adherence to therapy was assessed by using Morisky 8-Item Medication Adherence Questionnaire in which lower score indicates better adherence. Graph pad prism version 6.0 was used for statistical analysis. Results: POC was higher in women compared to men. No correlation was observed between POC and age (r = 0.01343, p= 0.9470) or daily dose of olanzapine(r= -0.2765, P = 0.1626). Patients having POC more than 20 ng/ml had better adherence (Morisky’s score 1 or 2) to medication compared to those having POC less than 20 ng/ml. Significant correlation was observed between POC and clinical response(r = -0.4371, p=0.0226). Conclusion: TDM of olanzapine is important considering large interpatient variability in POCs at the same dosages. It can also help in improving efficacy, particularly when patients do not respond to therapeutic doses or when they develop adverse effects. Cost of the procedure is a major concern which needs to be considered before this can be established in routine practice. Keywords: TDM, Antipsychotics, BPRS, LCMS, Schizophrenia.