Is therapeutic drug monitoring of risperidone a useful tool to predict clinical response and side effects in first-episode psychosis?

Bustillo, M. 1 , González-Pinto, A. 1, 2, 3 , Zabala, A. 1, 3, 4 , Segarra, R. 1, 3, 4, 5 , Alonso, M. 3, 6 , Eguíluz, J. I. 1, 3, 4, 5 , Ugarte, A. 2, 3 , del Río, D. 6 , Santos, B. 1 & Gutiérrez, M. 1, 2, 3

1 Department of Neuroscience, University of the Basque Country UPV/EHU
2 Department of Psychiatry, Santiago Apóstol University Hospital, Álava
3 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM
4 BioCruces Health Research Institute
5 Department of Psychiatry, Cruces University Hospital, Biscay
6 Department of Psychiatry, Donostia University Hospital, Guipúzcoa,

Purpose:
To investigate in a sample of first-episode psychosis(FEP) patients the relationship between dose, and plasma concentrations of risperidone and its association with clinical efficacy and side-effects.

Methods:
Twenty-one FEP patients treated with risperidone who had plasma concentrations and clinical measures at month 2 were selected. Clinical data were obtained using standardized rating scales. Plasma levels were quantified by HPLC-tandem mass spectrometric detection methods(HPLC/MS/MS). Correlation analyses and mixed-effects regression models were performed.

Results:
Mean age was 26.5(±5.7), and mean oral dose 4.7mg/day(±1.6).Although a correlation was found between dose and 9-OH-risperidone concentrations (r=0.563,p=0.008) -risperidone?s active metabolite-, no other association was detected between dose and risperidone or active moiety levels (risperidone plus 9-OH-risperidone). The mixed-effects model for 9-OH-risperidone levels confirmed that, aside from the dose (beta=4.23,p=0.007), no other variable resulted significant in predicting 9-OH-risperidone concentrations (age, gender, weight, cigarettes/day, cotinine levels, and consumption of antidepressants).
No correlation was found between percent decrease in total PANSS or scores in UKU-Side-effects Rating Scale and plasma levels of risperidone, 9-OH-risperidone or active moiety.

Conclusions:
Risperidone is rapidly metabolized to 9-OH-risperidone, so the majority of patients showed higher concentrations of 9-OH-risperidone than of risperidone. Therefore, 9-OH-risperidone concentrations may be more representative of the dose. However, it does not appear to be any association between plasma concentrations of risperidone, its metabolite, active moiety and clinical improvement or side-effects.