Discussion:
Currently, not enough data exists on the safety of many medications in pregnancy [11]. This lack of safety information in practice leads to patients having access to only a limited number of medications when they get pregnant, which are often old, less safe, and less effective [5].
Unfortunately, information on whether a medication is safe to use in pregnancy is difficult to come by and is mostly obtained from following patients who unexpectedly get pregnant while taking a certain medication, thus already exposing the fetus to the medication [12]. These cases are not easy to find, which is why the group of patients counseled and followed by our FRAME program provides us with invaluable knowledge on what happens when pregnant patients are exposed to medications.
The US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) released new requirements to encourage inclusion of female participants in clinical research [13,14]. Despite these guidelines, the enrollment of pregnant populations and women of reproductive age in clinical trials continues to be poor, leading to a lack of accurate pregnancy-specific prescribing information. [4,5,6,1,2,15,16,17]. Even if a medication is believed to not represent a risk for the developing fetus, many questions on the pharmacology of drugs in pregnancy remain, which can affect drug response and risk for toxicity. During pregnancy, a variety of physiological changes take place which can impact drug metabolism [18] and can lead to drug serum concentrations outside of their therapeutic windows. In these instances, utilizing standard dosing regimens (which were defined in non-pregnant people) can produce unexpected therapeutic failures or toxicities.
Various studies show that PTSD is prevalent in pregnancy [6] and that maternal PTSD is associated with negative birth or child outcomes, like low birthweight, preterm birth, and less mother-infant bonding [19]. Well controlled studies in non-pregnant subjects have reported that Prazosin results in significant improvement in the number of PTSD symptoms, including PTSD-associated nightmares [ 20,21, 22]. Despite this finding, there are still very few and adequate studies that exist for the safety of Prazosin use in pregnancy, and virtually no data available on safety of exposure to this drug in the first trimester.
A systematic review conducted by Davidson et al. (2021) [8] looked at pregnancy Prazosin exposures, but could only locate one randomized-control trial (conducted in the third trimester of pregnancy) and 5 cohort studies studying Prazosin use during late pregnancy and lactation. As the indication for use of Prazosin was mostly for maternal hypertension, the role of the underlying condition should be considered in adverse outcomes. The authors of this review noted that Prazosin may have a greater bioavailability and slower elimination in pregnant patients and may possibly lead to hypotension when given to patients who are normotensive and taking Prazosin for PTSD, which may cause fetal effects. This systematic review failed to find any reports for the use of Prazosin for the indication of PTSD, and provided few reports with regards to Prazosin’s use for other indications in the perinatal time period. The authors concluded that it is best to avoid this drug in pregnant patients due to the lack of safety information[8].
One of the studies cited in the Davidson review [8] was a 1983 study that looked at Prazosin use in 8 sujects in the last trimester of pregnancy [23]. This study found that Prazosin was effective for blood pressure control and outcomes suggested safety when used in the last trimester in these women. These data, although older, is still been used for reference when looking at Prazosin safety. The fact that a study with a small sample size conducted in 1983 is still one of the only studies that can be referred to when looking at Prazosin exposure during pregnancy illustrates the lack of data that currently exists. However, it is important to highlight that there are no data on the safety (or effectiveness) of Prazosin use in the first trimester of pregnancy.
The data presented in our study is the first case series to evaluate this topic. We did not observe any malformations in the newborns, and the babies that required brief NICU admission were reported to be doing well according to mothers who were contacted at follow up, with mothers reporting normal development of these babies and the NICU admissions being required as a precaution. There was no indication that the neonatal complications were related to Prazosin exposure, or that the rate of NICU admissions differed from that of the general population. Overall, birthweights in the population studied were within normal ranges for gestational age, and none were classified as low birthweight (i.e. <2500g). With regards to additional fetal outcomes, the proportion of miscarriages (18.2%) did not exceed expected rates based on normal population proportions [24].
It should be acknowledged that PTSD itself may lead to an elevated risk of poor outcomes. Ferri at al. (2007) found that PTSD during pregnancy was significantly associated with low birth weight [25]. A study conducted by Seng et al (2011) study also found that maternal PTSD was significantly associated with obstetrical complications such as shorter gestation and lower birthweight [26]. This is something to keep in mind with regards to the adverse outcomes reported in our study, given that there may be reason to expect elevated risk for reasons other than Prazosin exposure.
Limitations of the present study include a small sample size, thus limiting analysis to descriptive findings, and the absence of a comparison group of women not exposed to Prazosin during pregnancy. Another limitation is the use of self-reported data, collected via phone call questionnaires, which could be subject to recall bias and social desirability bias. The above could limit the ability to make any conclusions regarding safety based on this one small case series. This study provides preliminary data on the effects of use of Prazosin for the treatment of PTSD during pregnancy; however, further research is definitely needed. Future studies of the use of this medication for this indication in pregnant women are warranted given the prevalence of this disorder in this population. With larger datasets, accompanied by statistical analyses and replicated studies, it may be possible to make more solid safety conclusions. If possible, this medication should still be avoided during pregnancy, due to its unknown safety profile. However, if a pregnant woman is exposed to this medication, the lack of adverse effects or pregnancy complications in this study is reassuring.
Conclusion: There is a lack of current research evidence regarding drug safety for pregnant women with PTSD. Our study addresses this lack of information by providing incremental data regarding first trimester exposure in a more recent time period to inform the literature and to guide future studies. Although a small sample, this study contributes observational data on the use of Prazosin for PTSD during pregnancy and represents an important starting point for amassing more data to improve the care of pregnant women experiencing this condition. Furthermore, our results also showed that there were no major congenital malformations in the cohort that would have raised concern with regards to this drug’s safety.
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