Evidence-Based Reviews

Avoiding malpractice while treating depression in pregnant women

Current Psychiatry. 2021 August;20(8):30-36 | doi:10.12788/cp.0154

Consider the risks of untreated mental illness as well as the risks of antidepressant exposure.

References

1. Palmsten K, Setoguchi S, Margulis AV, et al. Elevated risk of preeclampsia in pregnant women with depression: depression or antidepressants? Am J Epidemiol. 2012;175(10):988-997.

2. Sit DK, Perel JM, Helsel JC, et al. Changes in antidepressant metabolism and dosing across pregnancy and early postpartum. J Clin Psychiatry. 2008;69(4):652-658.

3. Grote NK, Bridge JA, Gavin AR, et al. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010;67(10):1012-1024.

4. Friedman SH. The ethics of treating depression in pregnancy. J Prim Health Care. 2015;7(1):81-83.

5. Friedman SH, Resnick PJ. Postpartum depression: an update. Women’s Health. 2009;5(3):287-295.

6. Liu Y, Kaaya S, Chai J, et al. Maternal depressive symptoms and early childhood cognitive development: a meta-analysis. Psychol Med. 2017;47(4):680-689.

7. Wisner KL, Sit DK, Hanusa BH, et al. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry. 2009; 166(5):557-566.

8. Friedman SH, Hall RCW. Antidepressant use during pregnancy: How to avoid clinical and legal pitfalls. Current Psychiatry. 2013;12(2):21-25.

9. Bar-Oz B, Einarson T, Einarson A, et al. Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors. Clin Ther. 2007;29(5):918-926.

10. Einarson A, Pistelli A, DeSantis M, et al. Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry. 2008;165(6):749-752.

11. Huybrechts KF, Palmsten K, Avorn J, et al. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014;370(25):2397-2407.

12. In re: Zoloft (sertraline hydrochloride) products liability litigation. MDL No. 2342. No. 12-md-2342. United States District Court, E.D. Pennsylvania. June 27, 2014.

13. In re: Zoloft (sertraline hydrocloride) products liability litigation. MDL No. 2342. United States District Court, E.D. Pennsylvania. December 2, 2015.

14. Kirsch N, Pacheco LD, Hossain A, et al. Medicolegal review: perinatal Effexor lawsuits and legal strategies adverse to prescribing obstetric providers. AJP Rep. 2019;9(1):e88-e91.

15. Anderson KN, Lind JN, Simeone RM, et al. Maternal use of specific antidepressant medications during early pregnancy and the risk of selected birth defects. JAMA Psychiatry. 2020;77(12):1246-1255.

16. Centers for Disease Control and Prevention. Use of the antidepressant venlafaxine during early pregnancy may be linked to specific birth defects. Published October 28, 2020. Accessed October 29, 2020. https://www.cdc.gov/ncbddd/birthdefects/features/venlafaxine-during-pregnancy.html

17. Wisner KL, Oberlander TF, Huybrechts KF. The association between antidepressant exposure and birth defects--are we there yet? JAMA Psychiatry. 2020;77(12):1215-1216.

18. Wasserstein RL, Lazar NA. The ASA statement on p-values: context, process, and purpose. American Statistician. 2016;70(2):129-133.

19. Lassen D, Ennis ZN, Damkier P. First-trimester pregnancy exposure to venlafaxine or duloxetine and risk of major congenital malformations: a systematic review. Basic Clin Pharmacol Toxicol. 2016;118(1):32-36.

20. Miller LJ. Ethical issues in perinatal mental health. Psychiatr Clin North Am. 2009;32(2):259-270.

21. Coverdale JH, McCullough JB, Chervenak FA. Enhancing decision-making by depressed pregnant patients. J Perinat Med. 2002;30(4):349-351.

22. Coverdale JH, McCullough LB, Chervenak FA, et al. Clinical implications of respect for autonomy in the psychiatric treatment of pregnant patients with depression. Psychiatr Serv. 1997;48:209-212.

23. Coverdale JH, Chervenak FA, McCullough LB, et al. Ethically justified clinically comprehensive guidelines for the management of the depressed pregnant patient. Am J Obstet Gynecol. 1996;174(1):169-173.

24. Wisner KL, Zarin DA, Holmboe ES, et al. Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry. 2000;157(12):1933-1940.

25. Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception. 2011;84(5):478-485.

26. Cooper WO, Willy ME, Pont SJ, et al. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol. 2007;196(6):544.e1-5.

27. Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295(5):499-507.

28. Centers for Disease Control and Prevention. Update on overall prevalence of major birth defects--Atlanta, Georgia, 1978-2005. MMWR Morb Mortal Wkly Rep. 2008;57(1):1-5.

Many physicians have seen advertisements that encourage women who took an antidepressant while they were pregnant and had a negative outcome to contact a law firm. These ads could make patients more reluctant to take prescribed antidepressants, and psychiatrists more hesitant to prescribe necessary medications during pregnancy—which is a disservice to the mother and child.

More recently, several headline-grabbing studies appeared to suggest that there is an increased risk to infants who are exposed to antidepressants prenatally. Unfortunately, many patients do not understand that replication of these studies is often lacking, and methodological and confounding issues abound. All of this makes it difficult for patients and their families to know if they should take an antidepressant during pregnancy, and for psychiatrists to know what to discuss about the risks and benefits of various antidepressants during pregnancy. This article reviews the rationale for treatment of depression in pregnancy; the risks of untreated depression in pregnancy, as well as the potential risks of medication; ethical issues in the treatment of depression in pregnancy; the limitations of available research; and best approaches for practice.

Risks of untreated depression in pregnancy

Pregnant women may have misconceptions about treatment during pregnancy, and psychiatrists often are hesitant to treat pregnant women. However, the risks of untreated depression during pregnancy are even greater than the risks of untreated depression at other points in a woman’s life. In addition to general psychiatric risks seen in depression, pregnant women may experience other issues, such as preeclampsia and liver metabolism changes.^1-2 Risks to the fetus related to untreated or partially treated mental health concerns include poor prenatal care related to poor self-care, an increased risk of exposure to illicit substances or alcohol related to “self-medication,” preterm delivery, and low birthweight (Table 1^3-8). Further risks for an infant of a mother with untreated depression include decreased cognitive performance and poor bonding with poor stress adaptation.^5,6 Thus, appropriate treatment of depression is even more important during pregnancy than at other times of life.

Potential risks of treating depression in pregnancy

When prescribing psychotropic medications to a pregnant woman, there are several naturally occurring adverse outcomes to consider. For example, miscarriages, stillbirths, and congenital malformations can occur without explanation in the general population. In addition, also consider the specific health history of the mother and the available research literature regarding the specific psychotropic agent (keeping in mind that there are ethical issues associated with conducting prospective research in pregnant women, such as it being unethical to withhold treatment to pregnant women who are depressed in order to have a control group, and that retrospective research is often confounded by recall bias). Potential risks to be aware of include miscarriage (spontaneous abortion), malformation (teratogenesis, birth defects), preterm delivery, neonatal adaptation syndrome, and behavioral teratogenesis (Table 1^3-8).

Selective serotonin reuptake inhibitors (SSRIs), the usual medication treatment of choice for depression, have at times been implicated in adverse pregnancy outcomes, but no strong evidence suggests they increase the miscarriage rate. Overall data are reassuring regarding the risk of malformation associated with SSRI use. Of note, the FDA had switched paroxetine from a Class C drug to a Class D drug after early reports of a potential 1.5% to 2% risk of fetal cardiac malformations compared with a 1% baseline risk in the general population (these FDA pregnancy risk letter categories have since been phased out).^9,10 Nevertheless, the absolute risk remains small. Another large study found that there was no substantial increased risk of cardiac malformations attributable to antidepressant use during the first trimester.¹¹

Lessons from a class action suit

Since we last reviewed pregnancy and antidepressants in 2013,⁸ several class action lawsuits against the manufacturers of psychotropic medications have been heard. Product liability actions brought against manufacturers are different from medical malpractice suits brought against individual physicians, which may result from lack of informed consent, suicide, or homicide.

One of the largest class action suits was against Zoloft (specifically Zoloft and Pfizer, since the brand manufacturer is responsible for the product insert information.)^12,13 At the time, sertraline was already commonly prescribed due to the relatively safe reproductive profile.

Continue to: Many of the more than 300...