Evidence map›Paper›PMID 40072331›Full record

ArticleEpilepsia2025

Evaluation of antiseizure medication concentration ranges in blood samples using an automated big data approach.

Mariam Nersesjan, Elke Hoffmann-Lücke, Eva Greibe, Per Hersom Aaslo, Lasse Kristoffer Bak, Lars Engers Pedersen, Palle Bach Nielsen Fruekilde, Anette Stark, Jakob Christensen, Andreas Brønden and 1 more

Abstract read
In one paragraph

Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mariam NersesjanDepartment of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.ORCID https://orcid.org/0000-0002-9975-6216
Elke Hoffmann-LückeDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Eva GreibeDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Per Hersom AasloThe Laboratory of the Danish Epilepsy Centre-Filadelfia, Dianalund, Denmark.
Lasse Kristoffer BakDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
Lars Engers PedersenDepartment of Clinical Biochemistry, Næstved, Slagelse and Ringsted Hospitals, Slagelse, Denmark.
Palle Bach Nielsen FruekildeDepartment of Clinical Biochemistry, Odense University Hospital, Odense, Denmark.
Anette StarkDepartment of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Jakob ChristensenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID https://orcid.org/0000-0002-9385-6435
Andreas BrøndenDepartment of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Jens Borggaard LarsenDepartment of Clinical Biochemistry, Holbæk Hospital, Holbæk, Denmark.ORCID https://orcid.org/0009-0008-3462-5849

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe aim of the study is to provide insight into the real-world use of therapeutic drug monitoring (TDM) for the most common antiseizure medications (ASMs).

methodsIn total, 137 586 samples from the period 2019-2023 were collected from the five main Danish laboratories performing TDM. A previously described algorithm developed to exclude abnormal TDM results from patient data was applied. This resulted in the inclusion of 84 951 samples from 53 406 patients. Concentration ranges were calculated as 10th to 90th percentiles for the datasets of the ASMs: brivaracetam, carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, topiramate, valproic acid, and zonisamide. The observed concentration ranges were compared to the established reference ranges from Danish laboratories, the International League Against Epilepsy (ILAE), and the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP). Furthermore, data were stratified based on sex, age groups (0-17, 18-64, and 65-100 years) and indication (all indications vs psychiatric indication).

resultsThe observed concentration ranges showed good overall concordance with reference ranges from Danish laboratories except for levetiracetam, whereas the ranges for brivaracetam, lacosamide, lamotrigine, levetiracetam, valproic acid, and zonisamide were different from the AGNP and ILAE guidelines. Age-related differences were identified for several of the drugs. The calculated range of lamotrigine was lower in samples requested from psychiatric departments compared to samples from non-psychiatric departments. SIGNIFICANCE: The applied automated approach can facilitate a fast and efficient method for comparing established reference ranges with nationwide TDM datasets, thereby allowing continual monitoring of laboratory reference ranges. The findings from this study suggest that the Danish reference range for levetiracetam should be reevaluated. Furthermore, dose adjustment may be relevant for levetiracetam, topiramate, and lacosamide to account for age-related changes in metabolism. The lower concentration range for lamotrigine in the psychiatric population indicates that it may be effective at lower concentrations in patients with bipolar disorder compared to patients with epilepsy.

Indexed as

AnticonvulsantsDrug MonitoringEpilepsyAdolescentAdultAgedAged, 80 and overCarbamazepineChildChild, PreschoolDenmarkFemaleHumansInfantInfant, NewbornLacosamideAnticonvulsantsCarbamazepineLacosamideLamotrigineLevetiracetamOxcarbazepinePhenobarbitalTopiramateValproic AcidZonisamideantiseizure medicationepilepsyretrospective cohorttherapeutic drug monitoringtherapeutic reference range

Identifiers

PMID40072331
PMCPMC12169409

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.