Treatment of Anxiety and Depression in Pregnancy – What do the Data Tell Us?

Treating anxiety and depression during pregnancy is a complex and crucial aspect of maternal healthcare. There are extensive data available on the safety of anti-anxiety and anti-depressant medications for pregnant women, and registries and database studies also play a role in monitoring drug safety.

We caught up with Meg Richards, PhD, MPH, Executive Director, Scientific Strategy at Panalgo to discuss the careful balance required when prescribing these medications to expectant mothers, data’s role in informing treatment, and how Panalgo’s Mother-Infant Linkage data analytics package can help enhance research efficiency and effectiveness in pregnancy studies.

Q: When did we first start to think about drugs in pregnancy?

A: The intense focus on drugs in pregnancy dates to the thalidomide disaster of the late 1950s/early 1960s. Thalidomide was a drug that was used in 46 different countries as a sedative and a medication for morning sickness. Untested in pregnant women and initially thought to be safe, it resulted in some pretty horrific birth defects such as flipper-like limbs called ‘phocomelia.’ Even if you weren’t alive in 1961, you’ve probably seen pictures of these heart-breaking deformities. Thanks to Frances Kelsey, then-reviewer at the FDA, thalidomide was not permitted to enter the United States. The birth defects associated with thalidomide led to the development of greater drug regulation and monitoring in many countries.

Q: Do we have a lot of data on women who take anti-anxiety or anti-depressant medications during pregnancy?

A: Yes, we have quite a bit of data. Women who are pregnant are generally excluded from clinical trials, so what we know about drug safety comes primarily from the post-approval use of a product. Over the years, there have been registries established to look at the impact of certain drugs on the pregnant mother, the developing fetus, and the outcome of the pregnancy itself. Often, these registries follow the baby (if a live birth occurred) for up to age two years because there are complications – often developmental – that may not become manifest until late infancy or toddlerhood.

The FDA Office of Women’s Health maintains a list of Pregnancy Exposure Registries[i], and there are 33 drugs for anxiety and or depression that are included in the National Pregnancy Registry for Antidepressants[ii]. The registry is managed by the Center for Women’s Mental Health at Massachusetts General Hospital, and their publications date all the way back to 1994.

Q: Are such registries the only option for looking at drug safety in pregnancy?

A: No, registries are not the only option; there are database studies, as well. Registries and database studies are distinct. A registry is a primary data collection effort, meaning that you are collecting new data that enable you to answer specific research questions. Registries can offer very rich insights into the mom-baby journey, but they are expensive to stand up and maintain. Insights can be delayed because you must wait for the data (and therefore, the evidence) to accumulate. A database study involves the use of secondary data such as electronic health records or administrative claims data, which are not as rich in terms of potential insights but less expensive than a registry. Database studies provide faster answers to your questions because you are looking at events that have already occurred. Registries are mostly prospective or forward-looking, whereas database studies are mostly retrospective (looking back in time) in nature. The FDA recognizes the value of both registries and database studies, and in their Post market Commitments/Post market Requirements Database[iii], you can see how sponsors are mandated to conduct one or both to inform the safety of a new product. Last time I checked, the FDA’s ‘PMR’ database included 229 pregnancy-related PMRs or PMCs, of which 87 specified a database study.

Q: Going back to moms who are pregnant and managing anxiety, depression, or both – what advice are they given?

A: That’s an important question. There’s a website called MotherToBaby[iv], which is a service of the non-profit Organization of Teratology Information Specialists (OTIS). MothertoBaby is a great source of evidence-based information on the benefit-risk of medications and other exposures during pregnancy and while breastfeeding. An article on the website titled, ‘Balancing Act: The importance of Medication Dose in Pregnancy’ kind of says it all: you must carefully balance considerations of the mother’s health and safety with those of her fetus and take into account that a pregnant woman metabolizes drugs in a different way than when she is not pregnant. Some providers counsel their pregnant patients to reduce the dosage of their anti-anxiety or antidepressant medications at certain times in the pregnancy, but a reduction in dose could mean heightened anxiety or mood swings for the mother and impact the fetus (or newborn, if the mother develops postpartum depression) in an even more harmful way than the drug itself. Decisions must be made on a case-by-case basis and tend towards using a single drug at the lowest effective dose, particularly during the first trimester, when the developing fetus is most vulnerable.

The good news is that overall, the risk of birth defects and other problems for babies of pregnant mothers who take antidepressants is very low[v]. Selective serotonin reuptake inhibitors, or SSRIs, are usually an option during pregnancy. SSRIs include citalopram (Celexa), sertraline (Zoloft), escitalopram (Lexapro) and fluoxetine (Prozac). Risks include high blood pressure for the pregnant person and premature birth, but these risks are small. Most studies show that SSRIs aren’t linked with birth defects. But an SSRI called paroxetine (Paxil) might slightly raise the risk of heart defects in babies when used during the first trimester. For that reason, most health care professionals do not recommend paroxetine during pregnancy.

Q: Does Panalgo have data, technology, or services to inform drug safety in pregnancy studies?

A: I’m so glad you asked because as of May 2024, we have all three! Through our recent partnership with a closed claims data provider, we can now deploy mother-infant linked data that are pre-embedded in our Instant Health Data (IHD) platform to help clients more efficiently and effectively conduct their retrospective database pregnancy studies.

The Mother-Infant Linkage (‘MIL’) data analytics package combines linked mother-infant data and the IHD tools to complete pregnancy studies with ease. You can even work with one of our trained analysts/pregnancy experts to assist you in interrogating this unique data asset and module.

MIL is a modified version of Panalgo’s Tessa Closed Claims data source, which includes a linking file that associates patient IDs from a mother to patient IDs from each live-birth infant. The data contain about 3 million mother-infant pairs. Our solution combines each mother-infant pair into a single “patient.” This allows users to query the data in a format that is already natively at the pregnancy-episode level. We also have a built-in algorithm for estimating gestational age, or you can bring your own. We believe this will be a game changer for sponsors needing to fulfill a post market commitment or requirement without incurring the high fees or complex logistics of outsourcing to a third-party vendor or CRO. Let us help you get your research done without the headaches of outsourcing!

Interested in learning more about how your team can leverage the MIL package to enhance your studies? Reach out today.

 

 

[i] https://www.fda.gov/consumers/pregnancy-exposure-registries/list-pregnancy-exposure-registries

[ii] https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/

[iii] https://www.fda.gov/drugs/postmarket-requirements-and-commitments/postmarketing-requirements-and-commitments-downloadable-database-file

[iv] https://mothertobaby.org/baby-blog/balancing-act-the-importance-of-medication-dose-in-pregnancy/

[v] https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/antidepressants/art-20046420