Switching pattern and dose adjustment of antidepressants before and during pregnancy

Archives of Women's Mental Health https://doi.org/10.1007/s00737-023-01355-8 ORIGINAL ARTICLE Switching pattern and dose adjustment of antidepressants before and during pregnancy Robiyanto Robiyanto1,2 · Marjolein Roos1 · Jens H J Bos1 · Eelko Hak1 Catharina C M Schuiling‑Veninga1 · Eugène P van Puijenbroek1,3 · Received: 23 March 2023 / Accepted: 25 July 2023 © The Author(s) 2023 Abstract The purpose of the study is to examine the switching pattern and dose adjustment of antidepressants (ADs) prescribed to women from six months before to six months during pregnancy in the Netherlands. The recorded dispenses or refills were collected from the University of Groningen IADB.nl pregnancy subset for all singleton pregnancies in which the mother received ≥ 1 prescription of an AD dispensed before pregnancy and was present in the database at least six months after conception. The rates of continuation, discontinuation, and switching between 2001 and 2020 were assessed for the ADs studied. The mean number of Defined Daily Doses (DDDs) of the most frequently continued ADs used was calculated both before and during pregnancy, and a paired t-test was used to test for significant changes. The continuation rates for AD users, especially for SSRI and SNRI continued users, increased over time from 27% and 19% (2001–2005) to 65% and 65% (2016–2020). The switching rate between ADs remained consistently low from the start of the study (2001–2005) at 2.0% to the end of the study (2016–2020) at 2.3%. Most women who switched between antidepressants during pregnancy received a different SSRI monotherapy (85%), followed by an SNRI (6%), a TCA (4%), and an “other AD” (4%). In most cases observed, the dose adjustment for the mean DDDs during pregnancy compared to the mean DDDs before pregnancy only changed little (less than 10%). Continued use of SSRIs among singleton pregnancies doubled over the study period. The low rate of AD switching and little changes in the DDD adjustment for most AD continuers indicate that pregnant women prefer to continue their prepregnancy medication rather than switch it. Most observed findings cohere with the Dutch national guidelines for antidepressant use during pregnancy. Keywords Antidepressants · Dose adjustment · Pregnancy · Switching pattern Introduction Depression during pregnancy is estimated to affect approximately 16.4% of women worldwide and the efficacy of antidepressants (ADs) has been proven, especially in combination with psychotherapy (Arroll et al. 2009; Okagbue et al. 2019). The global prevalence of AD use during pregnancy was estimated at 3% for selective serotonin reuptake inhibitors (SSRIs), followed by serotonin and norepinephrine reuptake inhibitors (SNRIs) at 0.73% and tricyclic antidepressants (TCAs) at 0.38% (Molenaar et al. 2020a). The indications of use for ADs during pregnancy are notably * Robiyanto Robiyanto Marjolein Roos Catharina C M Schuiling‑Veninga 1 Jens H J Bos Unit of PharmacoTherapy, Epidemiology, & Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands 2 Eelko Hak Program Studi Farmasi, Fakultas Kedokteran, Universitas Tanjungpura, Pontianak, Indonesia 3 Netherlands Pharmacovigilance Centre Lareb, ‘s‑Hertogenbosch, The Netherlands Eugène P van Puijenbroek 13 Vol.:(0123456789) R. Robiyanto et al. for depressive or anxiety disorders (Zorginstituut Nederland 2022a, 2022b). Untreated perinatal depression or anxiety disorders during pregnancy appear to be unfavorable and inevitable, including the risk of relapse, preterm birth, low neonatal weight, and postnatal complications (ACOG 2008). In the Netherlands, the national guideline on the use of SSRI and non-SSRI antidepressants during pregnancy was initiated by the Dutch Association for Obstetrics and Gynecology (“Nederlandse Vereniging voor Obstetrie en Gynaecologie” (NVOG)) together with the Dutch Associations for Pediatrics (“Nederlandse Vereniging voor Kindergeneeskunde” (NVK)) and the Dutch Association for Psychiatry (“Nederlandse Vereniging voor Psychiatrie” (NVvP)) (NVOG 2012, 2021). Before the NVOG guideline was published in 2012, the first advice on ADs during pregnancy had been mentioned in 2005 by the Teratology Information Service of the National Pharmacovigilance Centre (Lareb) in the “Commentaren Medicatiebewaking” used by physicians and pharmacists as a practical reference book when prescribing and dispensing medicines (Stichting Health Base 2020). Both existing recommendations from NVOG and Lareb explain that there is no solid evidence for discontinuing ADs during pregnancy based on the risk they pose when the mother is stable and well-adjusted to the medication they are taking compared to the possible risk of relapse (NVOG 2012; Bijwerkingen Centrum Lareb 2021a). In any case, stopping or switching medication abruptly during pregnancy is not advised due to increased relapse/recurrence risk (Bijwerkingen Centrum Lareb 2021a, 2022; NVOG 2021). Detailed information for which AD medication should be switched and which AD requires a dose adjustment during pregnancy is not explicitly stated in both recommendations. In 2018, a study in France reported that switching between ADs occurred in 9.1% of all exposed pregnancies, and sertraline was mentioned as the most switched-to drug, followed by es-/citalopram (Bénard-Laribière et al. 2018). In the Netherlands, switching patterns and dose adjustments of ADs around pregnancy remain insufficiently explored. In this study, we aimed to elucidate trends in continuing use of ADs, switching patterns between ADs, and DDD adjustment of AD prescription before and during pregnancy. The findings were compared to the existing professional advice in the Netherlands to evaluate if there is an alignment between the observed trends and the Dutch national guidelines. Methods Setting, study population A retrospective drug utilization study was performed using the pregnancy subsection of the University of Groningen 13 IADB.nl longitudinal database for recorded dispenses (IADB.nl 2022). The general population in the IADB.nl was reported to represent the Dutch population overall (Visser et al. 2013; Sediq et al. 2018). From 1994 to 2021, this database had more than 2.7 million prescriptions dispensed from over 120 community pharmacies which covers more than 1.2 million people residing in the northeastern Netherlands. The prescription dispensed in the IADB.nl includes information, e.g., dispensing date, quantity and duration of drug prescribed, dose regimen, drug prescriber, and drug’s Anatomical Therapeutic Chemical (ATC) code. Dispensing data from hospital pharmacies or over-the-counter (OTC) medication are not recorded in the IADB.nl (IADB.nl 2022). The pregnancy subset in the IADB.nl uses a linkage/coupling approach in which a mother is linked to her child (both are anonymous patients) based on the address code and the mother’s age at delivery. This strategy (...truncated)