Psychotropics While Breastfeeding: Balancing Maternal Mental Health and Infant Exposure

Breastfeeding is known to be the optimal source of nutrition for infants, with well-established benefits for both mother and child. But clinical decision-making becomes complex when a breastfeeding mother is struggling with mental health issues and requires psychotropic medications. When prescribing any medication to lactating women, clinicians face the challenge of balancing the benefits and risks to both the mother and the infant. Psychotropics are just one of many classes of medications where clinicians must weigh this risk–benefit ratio, but the benefits are clear: helping to manage mental health diagnoses such as depression, anxiety, and psychosis is of the utmost importance to optimise maternal-child health. But what are the risks, and are they outweighed by the benefits? The first step to answering this question is to obtain accurate population-based data on psychotropic medication exposure among breastfed infants. In this issue of Paediatric and Perinatal Epidemiology, Liu and colleagues' study from Denmark [1] addresses this question. This commentary will discuss some of the epidemiologic insights learned from the study, the methodologic considerations that must be made when interpreting the data, and the potential medical implications of the study's results. The authors analysed almost 450,000 exclusively breastfed infants born between 2012 and 2022 to approximately 330,000 women. The authors used data on filled maternal psychotropic prescriptions as a proxy for potential exposure to infants, finding that 1.8% of infants (1 in 57) had potential exposure to any psychotropic medication via breastmilk, and 0.15% were potentially exposed to 2 or more. Several key epidemiologic trends emerged. First, they found a striking chronological trend. The prevalence of potential exposure increased by approximately 40% overall, from 15.7 per 1000 infants in 2012 to 21.8 per 1000 infants a decade later. While anxiolytics did not increase, sedatives/hypnotics and antidepressants increased by approximately 30%, antipsychotics by 70% and psychostimulants by 680%. Second, antidepressants not only increased over time, but accounted for the vast majority of potential exposures. To put this in perspective, antidepressant exposure occurred in 15 per 1000 infants, while the next most prevalent exposure was hypnotics and sedatives at 1.3 per 1000 infants. The most common were sertraline and citalopram, both selective serotonin reuptake inhibitors (SSRI). Third, the prevalence varied by maternal and infant characteristics. Perhaps not surprisingly, exposure was substantially higher when mothers had a known history of a psychiatric diagnosis or had previously been treated with a psychotropic medication. Interestingly, the overall prevalence increased with increasing maternal age, except for psychostimulants, with peak exposure for younger mothers. In addition, the study found that psychotropic exposure was inversely associated with the duration of breastfeeding and was higher for those born preterm or low birthweight (LBW), although whether the association is causal remains unclear. Denmark is uniquely situated for this large-scale, population-based pharmacoepidemiological research. Residents have free access to healthcare via a tax-funded healthcare system. Each resident is assigned a unique personal identifier that allows linkage across several national medical registries. The authors were therefore able to identify individual-level patient data on maternal–infant dyads, such as in- and outpatient visits, psychiatric care, filled prescriptions, and duration of exclusive breastfeeding. The study timeframe started after many of the registries, including the Danish Child Health Register, became mandatory, ensuring near-complete capture of data on included subjects. However, limitations exist that could impact the conclusions drawn from the data. The study focused exclusively on breastfed infants, potentially missing the substantial number of infants who are partially breastfed and underestimating exposure. Additionally, the study used filled maternal prescriptions as a proxy for exposure, hence “potential exposure,” but as noted, data on actual medication use, dose, or adherence were not available. Medication non-adherence is common, especially with psychotropic medications. A recent international meta-analysis found that psychotropic medication adherence was around 50% for those with major psychiatric disorders [2]. Although literature on adherence during breastfeeding is limited, studies have shown that adherence to antidepressants during pregnancy is also low and varies by medication class. One Canadian study found that only 40% of women prescribed antidepressants were adherent during their full pregnancy [3], while a Japanese study found that only 19% of women with antidepressant prescriptions before pregnancy adhered to this medication throughout their pregnancy [4]. This limited adherence may be due to maternal concern for impacts on the developing foetus, so it stands to reason that mothers may have similar concerns for risks to their baby during breastfeeding. This study demonstrates that while still affecting a very small percentage of infants, psychotropic medication exposure is becoming increasingly common. However, the most important question remains unanswered: how does this exposure impact the short- and long-term outcomes of the infants? The findings that most exposures involved antidepressants, namely SSRIs, may be reassuring. This aligns with the American College of Obstetrics and Gynecology (ACOG) practice guideline, noting that SSRIs are considered first-line medications for the treatment of perinatal depression or anxiety disorders [5]. SSRIs tend to have a lower relative infant dose (RID), a value that compares the dose received by the infant via breast milk to the maternal dose, with a lower RID indicating lower exposure. However, studies have found that maternal dosage and serum levels do not predict drug concentrations in maternal milk, noting that measuring drug concentrations in milk is a better predictor of exposure [6]. The significant rise in psychostimulants is particularly noteworthy. Although still relatively rare, there was an almost 7-fold increase over time, with the highest exposure in young mothers. While in utero psychostimulant exposure has not been shown to meaningfully increase the risk of childhood neurodevelopmental disorders [7], more data are needed on this and the impact of exposure via breastmilk. A concerning finding, and one that has been shown in prior studies, is that psychotropic exposure was inversely related to the duration of breastfeeding. Without clear data, mothers must weigh the potential risks of medication exposure to the baby during breastfeeding against the known risk of exacerbating mental health diagnoses by either stopping, changing, or not starting psychotropic medications. Given this choice, many may opt to limit or stop breastfeeding. What is clear is that healthcare providers must provide evidence-based, comprehensible, and non-judgmental information and support mothers with shared decision-making. Another concerning finding is the increased prevalence of exposure for preterm and LBW infants. Did the mother have a mental health exacerbation brought on by stress after a preterm delivery, leading to a psychotropic prescription? We know that mothers of preterm infants experience significant stress, which correlates with the level of infant illness [8]. Or did the mother's diagnoses and/or medication impact the timing of delivery and growth? Women with depression during pregnancy, even those undergoing treatment with antidepressants, have been shown to have increased odds of preterm delivery [9, 10]. Both are extremely important to explore further to minimize preterm LBW deliveries and optimize neonatal health. Moving forward, we desperately need longitudinal studies that include pharmacokinetics to define actual infant exposure as well as short- and long-term outcomes of maternal and infant health. This will aid in creating regulatory thresholds for safe exposure, providing clarity for physicians and patients, and expanding decision-support tools to guide real-time treatment decisions. The author takes full responsibility for this article. The author has nothing to report. The authors declare no conflicts of interest. The author has nothing to report.

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