Antipsychotic plasma concentration as predictor of movement disorders and cardiometabolic side-effects: A comparison with prescription dose
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.
Authors
- Selene Veerman
- Truus van den Brink
- Anton B. P. Staring (ORCID: https://orcid.org/0000-0002-4421-3265)
- Yinzhao Liu (ORCID: https://orcid.org/0000-0002-4156-4852)
- Gunnar Faber
- Marieke Begemann (ORCID: https://orcid.org/0000-0001-6448-2799)
- Martin D. de Jonge
- Ellen Graveland
- Matej Djordjevic
- Machteld Marcelis (ORCID: https://orcid.org/0000-0003-0045-9244)
- Martijn Kikkert
- Simone Kamphuis
- Sybren Wiersma
- Shiral S. Gangadin (ORCID: https://orcid.org/0000-0002-0084-8226)
- W. Veling
- Natalie D. Veen
- Joelle Hoornaar
- Toon Anton Willem Scheurink (ORCID: https://orcid.org/0000-0002-2944-2924)
- Karin Huizer (ORCID: https://orcid.org/0000-0002-0932-8139)
- Jörg Kurkamp
- Alban Voppel
- Georgios Schoretsanitis (ORCID: https://orcid.org/0000-0002-3851-4117)
- Priscilla P. Oomen (ORCID: https://orcid.org/0000-0001-8430-0905)
- Henderikus Knegtering
- Ben F. M. Wijnen (ORCID: https://orcid.org/0000-0001-7993-1905)
- Franciska de Beer
- Iris M. H. Hamers (ORCID: https://orcid.org/0009-0007-0296-3969)
- I. Sommer (ORCID: https://orcid.org/0000-0002-2682-5313)
- Filip Smit
- Gerdina Hendrika Maria Pijnenborg
- Jort Noorman
- Ruben Curfs
- Marieke J H Begemann
- Jim van Os
- Inge Hobus
- Therese van Amelsvoort
- P.Roberto Bakker
- Joran Lokkerbol
- Nynke Boonstra
- Koen Grootens
- Sanne Koops
- P Roberto Bakker
- Steven Berendsen
- Jan-Jaap Hage
- Nico van Beveren
- Hag Erna van ’t
- Lieuwe de Haan
- Bodyl Brand
- Toon A W Scheurink
- Maarten Bak
- Albert Batalla
Institutions
- University Medical Center Groningen (NL)
- Erasmus MC (NL)
- Zucker Hillside Hospital (US)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- European Neuropsychopharmacology
- Published
- 2026-01-22
- DOI
- https://doi.org/10.1016/j.euroneuro.2026.112769
- Primary Topic
- Schizophrenia research and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00