Antipsychotic plasma concentration as predictor of movement disorders and cardiometabolic side-effects: A comparison with prescription dose
Hamlett - Ophelia Consortium
Hamlett - Ophelia Consortium
Abstract
The clinical evidence for antipsychotic (AP) therapeutic drug monitoring (TDM) in evaluating AP-related movement disorders and cardiometabolic side-effects remains inconsistent. This study evaluates how AP plasma concentrations associate with movement disorders and cardiometabolic side-effects over time, and compares its predictive value to prescription dose in first-episode psychosis (FEP) patients. We included 200 remitted FEP patients from the HAMLETT trial. AP plasma concentrations were standardized using robust z-scores to accommodate different AP types. The St. Hans Rating Scale and Barnes Akathisia Rating Scale assessed movement disorders. Cardiometabolic indices included body mass index, waist circumference, blood pressure, glucose, triglycerides, and cholesterol. We evaluated longitudinal associations between plasma concentrations, movement disorders and cardiometabolic side-effects using two-part and linear mixed-effects models, and compared its predictive value to prescription dose using Bayesian Information Criterion (ΔBIC). Over a median 6-month follow-up (range = 0–48), AP plasma concentrations were positively associated with odds for parkinsonism (OR = 1.81, 95 % CI 1.27, 2.57, p = 0.001). No associations were found with tardive dyskinesia, akathisia, tardive dystonia, or cardiometabolic indices. AP plasma concentrations predicted parkinsonism better than prescription dose (ΔBIC = -2.95), but showed lower predictive value for waist circumference (ΔBIC = 3.22), total cholesterol (ΔBIC = 3.70), low-density-lipoprotein cholesterol (ΔBIC = 2.14) and non-high-density-lipoprotein cholesterol (ΔBIC = 5.46). These findings suggest that in remitted FEP patients, AP TDM may be more useful than dose in evaluating parkinsonism, likely because plasma concentrations more closely reflect free drugs at striatal dopamine receptors, but it does not appear useful for cardiometabolic side-effects.
Description
Members of HAMLETT and OPHELIA Consortium Prof. Dr. Iris Sommer, Prof. Dr. Lieuwe de Haan, Prof. Dr. Wim Veling, Prof. Dr. Jim van Os, Prof. Dr. Filip Smit, Dr. Marieke Begemann, Dr. Sanne Koops, Prof. Dr. Machteld Marcelis, Dr. Martijn Kikkert, Prof. Dr. Nico van Beveren, Prof. Dr. Nynke Boonstra, Bram-Sieben Rosema, Dr. P. Roberto Bakker, Dr. Sinan Gülöksüz, Dr. Joran Lokkerbol, Dr. Ben Wijnen, Dr. Bodyl Brand, Dr. Shiral Gangadin, Erna van ’t Hag, Dr. Priscilla Oomen, Dr. Alban Voppel, Franciska de Beer, Sterre Kamphuis, Iris Hamers, Matej Djordjevic, Toon Scheurink, Jort Noorman, Prof. Dr. Therese van Amelsvoort, Dr. Maarten Bak, Dr. Steven Berendsen, Truus van den Brink, Dr. Gunnar Faber, Prof. Dr. Koen Grootens, Martin de Jonge, Dr. Henderikus Knegtering, Dr. Jörg Kurkamp, Prof. Dr. Gerdina Hendrika Maria Pijnenborg, Dr. Anton Staring, Dr. Natalie Veen, Dr. Selene Veerman, Sybren Wiersma, Dr. Albert Batalla, Ruben Curfs, Jan-Jaap Hage, Ellen Graveland, Joelle Hoornaar, Inge Hobus, Dr. Karin Huizer
Date
2025
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Research Projects
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Keywords
Antipsychotic agents, Therapeutic drug monitoring, Metabolic syndrome, Extrapyramidal side effects
Citation
Hamlett - Ophelia Consortium 2025, 'Antipsychotic plasma concentration as predictor of movement disorders and cardiometabolic side-effects : A comparison with prescription dose', European Neuropsychopharmacology, vol. 105, 112769. https://doi.org/10.1016/j.euroneuro.2026.112769
License
info:eu-repo/semantics/openAccess