Antidepressants and PPHN
Antidepressants & Persistent Pulmonary Hypertension of the Newborn
A benchmark report released in 2006 stated that SSRI use after the 20th week of pregnancy is associated with an heightened risk of the newborn developing a rare and serious abnormality called persistent pulmonary hypertension of the newborn (PPHN). PPHN is the failure of the normal circulatory transition that occurs after birth, characterized by low pulmonary blood flow, severe respiratory failure, hypoxemia, and right-to-left shunting of blood. Six more studies addressing this association have been published since the 2006 report; however, all have contradicting results, leading to uncertainty regarding the association. In December of 2011, the U.S. Food and Drug Administration (FDA) reviewed the reports regarding the association and released the following statement: “Given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN.” The FDA further advised health care professionals to continue their current practices when treating depression during pregnancy, being careful not to let the small risk of PPHN steer them away from under-treatment or no treatment at all.4
Antidepressants While Pregnant: After 20 Weeks, the Risk Increases
According to the article “Antidepressants and Persistant Pulmonary Hypertension of the Newborn” by Director of the Mood Disorders Program at Thomas Jefferson University in Philadelphia, Rajnish Mago, M.D., when an outcome is rare, a very large number of patients with and without the risk factor must be followed in order to evaluate whether patients with the risk and those without are equally at risk of developing the outcome. However, early in an analysis, it is not practical to study large numbers of patients—instead a case-control study should be used, as they are appropriate for initial investigations of rare outcomes.5 According to Mago, as case-controls often may have certain problems, such as recall bias where patients are more likely to remember exposure to risk factors compared with controls, findings of such studies should be followed up with large cohort studies.5 In cohort studies, both patients with and without the risk factors are identified and followed up with to determine if they developed the outcome or not.5
The report given to the FDA in 2011 did not include two additional studies that were recently published regarding large cohort studies that did in fact find an association between the use of SSRIs and PPHN.4 Therefore, all four studies with a substantial number of infants with PPHN did find a significant association between maternal use of antidepressants and PPHN in the infant. The other three studies only included a limited number of infants with PPHN, all of whom did not have a significant association.
Pregnancy & Antidepressants
Mago states that it is important to keep in mind that there is a small risk, about 0.05 to 0.1 percent, of PPHN developing in newborns if the mother was treated with an SSRI during pregnancy.5 The risk increases during the later weeks of pregnancy, but may also be boosted by early pregnancy use as well.5 There were no differences found between different SSRIs and the risk of PPHN. Tricyclic antidepressants are known to have higher rates of congenital malformations and a variety of neonatal complications; therefore, they are not recommended as replacement treatment.8 Also, untreated depression may have its own negative consequences on pregnancy, and little to no treatment is also not recommended.5 In fact, Mago states that bupropion is safer, and psychotherapy is another alternative to SSRIs.5
 Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med. 2006;354:579-587.
 Occhiogrosso M, Omran SS, Altemus M. Persistent pulmonary hypertension of the newborn and selective serotonin reuptake inhibitors: lessons from clinical and translational studies. Am J Psychiatry. 2012;169:134-140.
 Källén B, Olausson PO. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Safe. 2008;17:801-806.
 US Food and Drug Administration. FDA Drug safety communication: selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm#data. Accessed June 14, 2012.
 Mago, R. (2012, August 2). Antidepressants and Persistent Pulmonary Hypertension of the Newborn. Psychiatric Times. Retrieved from http://www.psychiatrictimes.com/display/article/10168/2094061.
 Kieler H, Artama M, Engeland A, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. BMJ. 2012;344:d8012.
 Andrade SE, McPhillips H, Loren D, et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf. 2009;18:246-252.
 Reis M, Källén B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med. 2010;40:1723-1733. Antidepressants.