The present study describes exposure to antidepressants during pregnancy, and the characteristics of the exposed pregnancies. We assessed the prescription and dispensation of antidepressants in a cohort of pregnant women in Catalonia. Among 99,605 pregnancies identified in 76,459 women, 14,815 pregnancies (14.9%) involved a prescription for antidepressants, corresponding to 13,556 women. In at least 5672 of these pregnancies (5.8% of all pregnancies and 38.2% of those who had a prescription), the medication was dispensed at the pharmacy.

Our research indicates a decrease in the prevalence of prescriptions and, by implication, adherence to antidepressants as pregnancy progresses, showing an increase after the end of pregnancy. The most prescribed type of antidepressants were SSRIs, and the most frequently prescribed active substance globally was paroxetine. However, sertraline showed a monthly prevalence prescription increase in the last few years of the observation period, first gradually, and then toward the tail end of the follow-up period, rather sharply. Most women had a prescription of one single antidepressant. The assessment of persistence in incident and prevalent users of antidepressants indicated high rates of antidepressant discontinuation during pregnancy. Specifically, incident users show more stable persistence curves over time and a higher persistence at week 40.

Comparing our results with other studies, antidepressant exposure during pregnancy seems to be much higher than in other European regions. For example, in France, dispensation of antidepressants was estimated at 1.8% during pregnancy, almost four points under the estimation of our cohort [32]. However, the use and prescription of antidepressants parallel the rates of anxiety and depression reported in previous studies in our region: both are the most common mental health conditions during pregnancy, with 12% of women reporting depression and 13% anxiety, often concurrently [33, 34]. Anxiety has also been one of the most frequently associated health conditions with antidepressant prescriptions in previous studies [35], similar to the results of our analysis. This fact aligns with indications for certain antidepressants in Spain, which also include treatment of anxiety [36, 37].

When set against other research, the sociodemographic characteristics of mothers in terms of age, toxic habits and socioeconomic context show certain similarities. The distribution of antidepressant prescription seems quite homogeneous among all socioeconomic quartiles in our cohort. Despite this, most of the exposed episodes belonged to the most deprived quartile according to the MEDEA socioeconomic index. Some research identifies low socioeconomic status as a risk factor for developing perinatal depression [38]. Women from wealthier quartiles might receive follow-up care in private settings. While prescriptions from primary care and public psychiatric services are captured in our data, those from private care are not, which may limit our ability to fully record these patients over time accurately.

Because the current database lacks a mother-child link, it was not feasible to analyse the impact of antidepressants on offspring during pregnancy, as done in prior studies [32]. Despite this limitation, we were able to analyse delivery outcomes, revealing that vaginal births were the most common (58.8%), though this percentage was lower than the 63.5% benchmark established by local perinatal health authorities [39], followed by abortions (spontaneous and induced) and 62 cases of prematurity. It should be noted that this later information is obtained either from the ICD-10 code or from the weeks of gestation, with many results imputed, based on the duration of a normal pregnancy.

The most prescribed type of antidepressants were SSRIs. According to the National Institute for Health and Care Excellence guidelines [40], which also inform Spanish recommendations [41], SSRIs are generally recommended for both mild and severe depression in the general population owing to their good safety profile and tolerability, without specifying any particular SSRI as first-line treatment. Recent studies suggest that while some antidepressants show slightly higher efficacy and adherence rates, no significant differences have been found among SSRIs in terms of effectiveness for treating major depressive disorder [42, 43]. While some SSRIs have been associated with adverse perinatal outcomes [44], it is important to interpret these findings within the broader context of maternal mental health and the methodological limitations of existing studies. In our study, paroxetine was the most frequently prescribed antidepressant, which is notable given earlier reports suggesting an increased risk of congenital malformations [15] and the warning issued by the US Food and Drug Administration in 2005 regarding the potential risk of cardiac malformations in babies when pregnant women were exposed to paroxetine during the first trimester [45]. However, these associations may be influenced by confounding by indication [10, 15], as women prescribed antidepressants may also present with more severe or poorly controlled mood disorders [5]. Our results are in line with those of a Danish study [47] where the increase in prescriptions in the period studied was mainly due to SSRIs.

In contrast, sertraline showed a monthly prevalence prescription increase in the last few years of the observation period. To our knowledge, there are no comparative safety studies demonstrating that sertraline is safer than other antidepressants during pregnancy. However, sertraline is recommended for use during pregnancy by multiple clinical guidelines, based on its overall safety profile, which includes both favourable infant outcome data and low concentrations detected in breast milk during breastfeeding [47, 48]. This fact, along with unfavourable data regarding the risk associated with paroxetine and fluoxetine [49], may have led prescribers to more frequently prescribe sertraline in recent years. Regarding multiple prescriptions, most women in our cohort were prescribed just one type of antidepressant, adhering to expert recommendations [2, 7].

Antidepressant prescription patterns by class group and by trimesters also closely resemble findings from other studies [20, 22, 32, 50]. These findings include the decrease of medication consumption as pregnancy progresses and the frequency of single antidepressant prescriptions [32]. It is noteworthy that there was a rise of prescription, dispensation, and adherence (dispensation by prescription rate) after the end of pregnancy, possibly also correlated to the diagnosis of postpartum depression [4,5,6]. Although most antidepressants are excreted in breast milk [51], the available evidence is reassuring because of the very low amount of antidepressant drug concentrations to which infants are exposed, and therefore, the observed increase in postpartum antidepressant use should not be considered concerning. At the time of conducting the present study, data on maternal breastfeeding were not available in our cohort and we do not have data of breastfeeding in our region. This issue should be assessed in future research.

In the case of pregnant women, primary adherence (dispensation by prescription rate) studies are scarce, but some of them indicate that many women discontinue their antidepressant once they become aware of the pregnant status [18]. Reports of the discontinuation of antidepressants during pregnancy over time is around 40% in previous studies [20, 22]. These studies suggest that the discontinuation ratio is higher in patients who were previously prescribed the medication [22]; however, it is important to consider that symptom severity may vary within this population. These observations might point toward a possible pattern: incident users could present with more acute symptoms, whereas prevalent users may have a more stable clinical profile. The discontinuation ratio also varies depending on the type of antidepressant prescribed, indicating a higher persistence for SNRIs and SSRIs compared with other antidepressants [20]. We assessed the above-mentioned hypothesis stated in previous research through persistence calculation. The difference in the Kaplan–Meier curves indicated that persistence was higher in those women defined as incident. This pattern constitutes a field to be addressed and expanded through observational studies and qualitative research.

Persistence to antidepressants throughout pregnancy seems to have been higher in other studies than in ours [22], indicating higher persistence rates in previous research. However, comparability with these studies is limited by various factors. First, the objectives of our article and other previous research differ. The factors that limit comparability also cover inclusion criteria: both studies only included women who had a prior diagnosis of depression. Additionally, definitions of discontinuation during pregnancy vary from one study to another (15 days and 1 month), and the total number of patients in the cohort is more limited than in our study. In those studies that did take 2 months as the definition for discontinuation [46], persistence was not compared between incident and prevalent patients, studying them globally. Discontinuation in our study was around 50%. Other recent investigations carried out in Europe have also reported, through modelling of longitudinal trajectories, different patterns of dispensing and dosing of antidepressants in the period around pregnancy [52].

In our cohort, during the post-partum period, 29.2% of women re-started antidepressant medication after stopping it during pregnancy, though the cause could not be identified. One recent report indicates that 17.6% of women who discontinued SSRIs during pregnancy restarted SSRIs during postpartum [50]. Other studies have reported on the risk of depression relapse in women who discontinue antidepressant treatment during pregnancy, which ranged from a five-fold increased risk [19] to no increased risk [53]. In a recent study based on data from Denmark and Norway, the authors report a lower probability of initiating psycholeptic agents or having postpartum psychiatric emergencies in those women who discontinued their medication (early or late discontinuation) versus those who continued taking it during pregnancy. The authors state that women who discontinued antidepressants early in pregnancy or discontinued late in pregnancy after short-term use may have less severe underlying disorders and can successfully stop their medications. In contrast, those who discontinued late in pregnancy after long-term use may have had more severe episodes and may benefit from an individual assessment before discontinuation [54]. These results should be further explored in future research, particularly by investigating the underlying reasons for antidepressant discontinuation using more specific methods to better capture women’s decision-making processes and clinical profiles.

Our study has several limitations. First, the impact on the offspring could not be estimated. Efforts to conduct this analysis will be made in future research. Second, estimating adherence through dispensation has the drawback of assuming that women who collected their medication took it (this may not reflect true medication usage). Third, our study did not examine concomitant medications such as anxiolytics, unlike other investigations [32]. This is itself a noteworthy point, considering that most women in our cohort had a diagnosis of anxiety. Finally, the differences between algorithms amongst databases to detect pregnancies complicate their comparability.

The strengths in our study include the following. The use of a verified database [24], ensuring the reliability of our data. The inclusion of many participants boosts the statistical power and permits more precise and generalisable results. We focused on describing precisely the sociodemographic characteristics of patients, allowing us to profile in detail our cohort. We estimated prescription, dispensation rates and primary adherence (dispensation by prescription rate) by trimesters. Furthermore, we estimated persistence and the medication reintroduction rate to understand properly the behaviour of prescribers and women in our cohort. No previous studies with similar characteristics have been conducted in this specific population, and to our knowledge, none has been performed in Spain.

Previous European studies have noted the need to identify barriers in healthcare services and prescribing behaviour to improve treatment. Risks of stopping treatment and exploring other options such as psychological interventions should be studied in rigorous trials [53]. The difference between prescriptions and dispensations found in our study is concerning, and it underscores the role of the quality of interactions with healthcare professionals in managing decisional conflict and supporting informed decision making in the context of perinatal mental health [55]. In this regard, our study highlights the use of large databases to record patient and prescriber behaviour, which could help regulatory authorities implement better prescription practices based on post-authorisation safety studies. The absence of clinical practice guidelines for peripartum depression in most European countries and the inconsistencies in recommendations can lead to disparities in managing peripartum depression [56]. Considering that untreated maternal depression during pregnancy can lead to emotional development disorders in the newborn [2], this factor is of particular interest.