Results
Title

Guiding safer risperidone prescribing in Alzheimer's disease with therapeutic drug monitoring.

Authors

Roughley, Matthew; Mena, Carlos; Howard, Robert; Reeves, Suzanne; Bertrand, Julie

Abstract

Previous analysis of pharmacokinetic data on risperidone‐treated patients with dementia predicted that 20% had concentration‐to‐dose (C/D) ratios of the active moiety (risperidone and 9‐hydroxy(OH)‐risperidone) above 14 ng/mL per mg/day, which were in turn associated with a greater risk of extrapyramidal side effects. This study aimed to further explore risperidone pharmacokinetics in a second dataset. Nonlinear mixed effects modelling, using a Bayesian approach, was applied to data from a randomized controlled trial of risperidone in people with dementia. Covariates included age and glomerular filtration rate (GFR). Age had a significant effect on risperidone clearance (β = −1.5) and GFR on 9‐OH‐risperidone clearance (β = 0.2). The model predicted that 26.2% (95% confidence interval 18.6‐32.6%) had C/D ratios above 14 ng/mL per mg/day. These findings confirm the importance of age‐related risperidone dose adjustments and argue strongly for therapeutic drug monitoring in the initial stages of treatment to identify those at greatest risk of toxicity.

Subjects

DRUG monitoring; ALZHEIMER'S disease; RISPERIDONE; DRUG prescribing; GLOMERULAR filtration rate

Publication

British Journal of Clinical Pharmacology, 2023, Vol 89, Issue 7, p2316

ISSN

0306-5251

Publication type

Academic Journal

DOI

10.1111/bcp.15692