The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies

Schoretsanitis G, Deligiannidis KM, Kasperk N, Schmidt CT, Kittel-Schneider S, Ter Horst P, Berlin M, Kohn E, Poels EM, Zutshi D, Tomson T, Spigset O, Paulzen M (2024)

Publication Type: Journal article, Review article

Publication year: 2024

Journal

Progress in Neuro-Psychopharmacology & Biological Psychiatry Elsevier

Book Volume: 133

Article Number: 111030

DOI: 10.1016/j.pnpbp.2024.111030

Abstract

Objective: Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics. Methods: A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines. Results: A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07–2.45, 0.42, range 0.08–0.82 and 0.52, range 0.04–2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10−3, 95%CI = -16.08 to −8.58 × 10−3 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to −4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to −0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10−3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10−3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5. Conclusions: Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.

Involved external institutions

Psychiatrische Universitätsklinik Zürich CH Switzerland (CH) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE) Tel Aviv University IL Israel (IL) Wayne State University (WSU) US United States (USA) (US) Zucker Hillside Hospital US United States (USA) (US) Isala Medical Centre NL Netherlands (NL) Karolinska Institute SE Sweden (SE) St. Olavs University Hospital / St. Olavs Hospital Universitetssykehuset i Trondheim NO Norway (NO) Cork University Hospital IE Ireland (IE) Erasmus University Medical Center (MC) NL Netherlands (NL)

How to cite

APA:

Schoretsanitis, G., Deligiannidis, K.M., Kasperk, N., Schmidt, C.T., Kittel-Schneider, S., Ter Horst, P.,... Paulzen, M. (2024). The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 133. https://doi.org/10.1016/j.pnpbp.2024.111030

MLA:

Schoretsanitis, Georgios, et al. "The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies." Progress in Neuro-Psychopharmacology & Biological Psychiatry 133 (2024).

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