Bustillo, M. 1 , Segarra, R. 1, 2, 3, 4 , Querejeta, I. 1, 3, 5 , González-Pinto, A. 1, 3, 6 , Zabala, A. 1, 3, 4 , García, J. 1, 2, 4 , Urgoiti, E. 5 , Ugarte, A. 3, 6 , Santos, B. 1 & Gutiérrez, M. 1, 3, 6
1 Department of Neuroscience, University of the Basque Country UPV/EHU
2 Department of Psychiatry, Cruces University Hospital, Biscay
3 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM
4 BioCruces Health Research Institute
5 Department of Psychiatry, Donostia University Hospital, Guipúzcoa
6 Department of Psychiatry, Santiago Apóstol University Hospital, Álava
Objectives:
a)To see which variables influence plasma levels in a sample of First-Episode Psychosis (FEP) patients.
b)To determine the validity of olanzapine plasma break-points previously proposed as clinical predictors of response to treatment.
Methods:
Twenty-five FEP patients who had plasma concentrations of olanzapine and clinical measures at 2 and 6-month follow-up were studied.
Clinical response to olanzapine was defined as ?20% reduction in PANSS scores from baseline. Plasma levels were quantified using HPLC-tandem mass spectrometric detection methods(LC/MS/MS). A mixed-effects linear regression model for olanzapine plasma levels with weight, age, gender, cigarettes/day, dose, antidepressants, and ?20% improvement in PANSS as covariates was performed. The plasma break-points we considered were the ones referred by Perry et al.(1999) and Fellows et al.(2003).
Results:
Mean age was 28.39(SD=7.75). Daily doses ranged from 2.5 to 20mg/day. Blood samples were obtained 10.53(SD=1.08 hours) after last intake. The following variables resulted significant: age(beta=1.02;p=0.028); cigarettes/day(beta=-0.81;p=0.023); and dose(beta=3.09;p=<0.001). The ?23 ng/ml break-point identified 89% of responders at month 2 and 76% at month 6, whereas 100% of non-responders were plotted above it.
Conclusions:
Age, number of cigarettes and dose may contribute to explain variability in Olanzapine plasma levels. The aforementioned plasma concentration break-point had high sensitivity but no specificity. We propose the use of more strict criteria for clinical response(e.g.40% PANSS reduction) to increase specificity.