This post is by Dr Adam Urato, a Professor of Obstetrics & Gynecology at Tuft’s University
Imagine for a moment that a virus started affecting about 5% of all pregnant women—200,000 US pregnancies per year. Imagine that it caused significant pregnancy complications–more than 10% of those infected with the virus would have miscarriage, up to 20% or more would have preterm birth, and 30% of newborns would show effects of the exposure in the days after birth—sometimes severe, with seizures and trouble breathing.
it would be a public health emergency
If this were to occur it would be considered a public health emergency and a tremendous effort would be put forth to address it. Yet this epidemic is happening and, in many ways, it is going unrecognized. Pregnant women and the public are unaware. It is the epidemic of antidepressant drug exposure during pregnancy.
Two articles came out recently showing that antidepressant use by pregnant women is associated with preterm birth (1, 2). One of them also showed increased rates of neonatal seizures in newborns who were exposed to antidepressants in utero. These articles join a large and growing body of literature that clearly demonstrates risks when pregnant women use antidepressants (3).
These risks are all the more concerning given that there is no evidence of improvement of pregnancy outcomes with the use of antidepressants by pregnant women. There is an important question to ask: Are we exposing millions of pregnant women and their babies to a class of drugs that are causing significantly more harm than good?
Current research suggests that antidepressant use (typically the SSRIs) by pregnant women is associated with increased risks of miscarriage (4), birth defects (5), preterm birth (1, 2), preterm premature rupture of membranes (6), preeclampsia (7), and decreased fetal growth (8). After birth, newborns who were exposed to antidepressants in utero have increased rates of what is called the newborn behavioral syndrome (9) which can consist of a variety of symptoms including tremors, agitation, excessive crying, respiratory difficulties, and seizures (1). Exposed newborns also have been shown to have changes in heart conduction (10) and a potentially fatal condition called Persistent Pulmonary Hypertension of the Newborn (PPHN) in which the arteries to the baby’s lungs are constricted leading to trouble breathing or, in severe cases, death (11).
Many of these risks are not rare. Rates of miscarriage in women taking antidepressants are estimated at greater than 10% (12). In some studies rates of preterm birth in the antidepressant exposed groups have been greater than 20% (13, 14). Ten percent of babies exposed to SSRIs in utero will show the prolonged QT syndrome on their EKG (10). And up to 30% of exposed babies will develop the newborn behavioral syndrome (9).
we are witnessing a large uncontrolled experiment on human development
What is particularly concerning in this area is the issue of possible long term effects on the developing brains of exposed babies. Developing embryos and fetuses are loaded with serotonin receptors and the serotonergic system plays a crucial role in fetal development. What happens to human development of the brain and behavior when we alter this system? We simply have no idea and we are currently witnessing what amounts to a large uncontrolled experiment on human development. The current research data is not reassuring. Animal data clearly shows that fetal exposure to antidepressants can lead to changes in the development of the brain and changes in behavior (15, 16). Studies are available that demonstrate effects on the branching of neurons–the basic cell in the nervous system (17). Human studies have shown that children who were exposed to antidepressant in utero have changes in motor development and behavior (18, 19). Last July (2011) researchers at Kaiser in California showed a doubling of the risk of autism with prenatal exposure to antidepressants (20). And this doesn’t appear to be a “chance” finding. For decades serotonin has been implicated in the etiology of autism (21).
there is no evidence of benefit
Many of these risks might be tolerable if there was evidence of pregnancy benefit with the use of antidepressants by pregnant women. “After all,” you might think, “cancer drugs have risks too but we use them because they cure cancer.” But, sadly, there is no evidence of obstetrical benefit with the use of these drugs by pregnant women. In study after study the group of women on the antidepressants have worse pregnancy outcomes, not better. For example, they have more miscarriages, more preterm birth, and more neonatal complications.
For years, the key opinion leaders in this area (most of whom are paid sizeable amounts by the drug industry) have been pitching the idea that pregnant women, by taking antidepressants, will improve their mood and that this will lead to better pregnancy outcomes. The conventional wisdom has been that depression is like diabetes and depressed pregnant women need to stay on their antidepressants just like pregnant diabetics need to take their insulin. And this counseling gets repeated on a daily basis in doctors’ offices around the globe and in news reports on this topic.
The problem is that it just isn’t true: pregnancy outcomes do get better when diabetics take their insulin but this isn’t true with antidepressants. We had all hoped that the pregnancies of depressed women could be helped with drugs, but the scientific literature does not support the idea that antidepressant use in pregnancy improves outcomes. In fact, it’s just the opposite. When you take a group of depressed pregnant women and compare them to depressed pregnant women taking antidepressants, it’s the group that is taking the antidepressants that has the increased rates of pregnancy complications.
what women need is accurate, correct, and complete information
So what should we tell pregnant women and women of childbearing age who are taking these drugs? As a Maternal-Fetal Medicine consultant, I deal with this issue regularly. And for me the key is transparency and properly informing the patients and the public. Who can argue with giving pregnant women full information about a drug they are taking? And the truth is that full information in this area means telling women that antidepressant use during pregnancy has been associated, in study after study, with pregnancy complications and no evidence of better pregnancy results.
I frequently give lectures on this topic and am asked “What about the woman with severe depression who is suicidal when she comes off her antidepressant?” To me, it sounds like she should stay on the medication. But, let’s be clear, the vast majority of women on these drugs have mild to moderate depression. Furthermore, my main point on this is not that we should be telling anyone what to do. Psychotropic medication use during pregnancy is a personal choice and these women need care and support. But what they also need is accurate, correct, and complete information so they can make an informed decision; that is not what is currently happening.
We are currently seeing what amounts to an epidemic of antidepressant drug exposure during pregnancy and there is a pervasive lack of public information and understanding on this topic. Pregnant women need accurate information about drugs they take. I am surprised on a regular basis by my colleagues in obstetrics and psychiatry who are simply unaware of the large body of scientific studies clearly showing antidepressants to be associated with pregnancy complications. What pregnant patients choose to do with this information is up to them, but patients and the broader public deserve to be told the truth about the risks of antidepressant use during pregnancy.
1. Hayes, R.M., Wu, P., Shelton, R.C., Cooper, W.O., Dupont, W.D., Mitchel, E., Hartert, T.V., Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies, American Journal of Obstetrics and Gynecology (2012), doi: 10.1016/j.ajog.2012.04.028.
2. Yonkers KA, Norwitz ER, Smith MV, Lockwood CJ, Gotman N, Luchansky E, Lin H, Belanger K. Depression and Serotonin Reuptake Inhibitor Treatment as Risk Factors for Preterm Birth. Epidemiology. 2012 May 23. [Epub ahead of print]
3. Urato AC. Antidepressants and Pregnancy: Continued Evidence of Harm—Still No Evidence of Benefit. Ethical Hum Psychol Psychiat 2011; 13: 190
4. Nakhai-Pour HR, Broy P, Bérard A. Use of antidepressants during pregnancy and the risk of spontaneous abortion. CMAJ. 2010 Jul 13;182(10):1031-7. Epub 2010 May 31.
5. Colvin L, Slack-Smith L, Stanley FJ, Bower C. Dispensing patterns and pregnancy outcomes for women dispensed selective serotonin reuptake inhibitors in pregnancy.Birth Defects Res A Clin Mol Teratol. 2011 Mar;91(3):142-52. doi: 10.1002/bdra.20773. Epub 2011 Mar 4.
6. Reis M, Källén B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med. 2010 Oct;40(10):1723-33. Epub 2010 Jan 5.
7. Toh S, Mitchell AA, Louik C, Werler MM, Chambers CD, Hernández-Díaz S. Selective serotonin reuptake inhibitor use and risk of gestational hypertension. Am J Psychiatry. 2009 Mar;166(3):320-8. Epub 2009 Jan 2.
8. Oberlander TF, Warburton W, Misri S, Aghajanian J, Hertzman C. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry. 2006 Aug;63(8):898-906.
9. Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006; 160:173-176.
10. Dubnov-Raz G, Juurlink DN, Fogelman R, Merlob P, Ito S, Koren G, Finkelstein Y. Antenatal use of selective serotonin-reuptake inhibitors and QT interval prolongation in newborns. Pediatrics. 2008 Sep;122(3):e710-5.
11. Kieler H, Artama M, Engeland A, Ericsson O, Furu K, Gissler M, Nielsen RB, Nørgaard M, Stephansson O, Valdimarsdottir U, Zoega H, Haglund B. 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 Jan 12;344:d8012.
12. Hemels ME, Einarson A, Koren G, Lanctôt KL, Einarson TR. Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis. Ann Pharmacother. 2005 May;39(5):803-9. Epub 2005 Mar 22.
13. Ferreira E, Carceller AM, Agogué C, Martin BZ, St-André M, Francoeur D, Bérard A. Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates. Pediatrics. 2007 Jan;119(1):52-9.
14. Latendresse G, Ruiz RJ. Maternal corticotropin-releasing hormone and the use of selective serotonin reuptake inhibitors independently predict the occurrence of preterm birth. J Midwifery Womens Health. 2011 Mar;56(2):118-26.
15. Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science. 2004 Oct 29;306(5697):879-81.
16. Xu Y, Sari Y, Zhou FC. Selective serotonin reuptake inhibitor disrupts organization of thalamocortical somatosensory barrels during development. Brain Res Dev Brain Res. 2004 Jun 21;150(2):151-61.
17. Lee LJ. Neonatal fluoxetine exposure affects the neuronal structure in the somatosensory cortex and somatosensory-related behaviors in adolescent rats. Neurotox Res. 2009 Apr;15(3):212-23. Epub 2009 Mar 4.
18. Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, Hoyme HE. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr. 2003 Apr;142(4):402-8.
19. Pedersen LH, Henriksen TB, Olsen J. Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age. Pediatrics. 2010 Mar;125(3):e600-8. Epub 2010 Feb 22.
20. Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry. 2011 Nov;68(11):1104-12.
21. Anderson GM, Horne WC, Chatterjee D, Cohen DJ. The hyperserotonemia of autism. Ann N Y Acad Sci. 1990;600:331-40; discussion 341-2.