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Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study

BMJ 2017; 356 doi: (Published 06 March 2017) Cite this as: BMJ 2017;356:j832

Genotyping women before pregnancy to prevent congenital heart defects induced by serotonin reuptake inhibitors? Personalized vs pragmatic medicine

Nembhard et al’s robust study showing genetic variants in folate, homocysteine, or transsulfuration pathways are associated with congenital heart defects among children of women taking selective serotonin reuptake inhibitors (SSRI) deserves comment.

First, kudos for their concern as the safety of drugs in this most vulnerable population is characterized by the paucity of investigations, even when serious adverse effects are documented.(2,3)

Second, this physio-pathological study may be missing the wood for the trees.

a) The efficacy of antidepressant during pregnancy deserves a re-evaluation. There are no adequate and well-controlled studies in pregnant women.(4) This issue cannot be by passed as: a) numerous trials deliberately misrepresented findings;(5-6) b) the efficacy of antidepressant is not observed in several specific population such as children and adolescents, chronic heart failure or alcohol use disorders.(7-11)
c) Congenital anomalies are the tip of the iceberg. SSRI also increased the risk of postpartum haemorrhage and, serious concerns for child's development are increasing (eg. autism spectrum, and attention deficit disorders).(4)
Drugs should not be the first option for any woman of childbearing age (teratogenicity can occur before women are aware they are pregnant): cognitive behavioural therapy (CBT) is effective against major depression without adverse effects.(2) There is an urgent need to extend an appropriate regulation (restricting prescription in women of childbearing age to specialists who must obtain signed consent) as recently done for epilepsy.(3)

1 Nembhard WN, Tang X, Hu Z et al. Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study. BMJ 2017;356:j832.

2 Braillon A, Bewley S. Paucity of data on the safety of drugs for treating depression in pregnancy. BMJ 2016;353:i2582.

3 Braillon A, Bewley S. Epilepsy in women during pregnancy. Lancet 2016;387:646

4 O'Connor E, Rossom RC, Henninger M, Groom HC, Burda BU Primary care screening for and treatment of depression in and postpartum women: Evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016 ;315:388-406.

5 Le Noury J, Nardo JM, Healy D et al. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ2015 16;351:h4320.

6 Jureidini JN, Amsterdam JD, McHenry LB. The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance. Int J Risk Saf Med 2016;28:33-43.

8 Cipriani A, Zhou X, Del Giovane C. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet 2016;388:881-90.

9 Angermann CE, Gelbrich G, Störk S et al. Effect of escitalopram on all-cause mortality and hospitalization in patients with heart failure and depression: The MOOD-HF randomized clinical trial. JAMA 2016;315:2683-93.

10 Foulds JA, Rouch S, Spence J, Mulder RT, Sellman JD. (2016b) Prescribed psychotropic medication use in patients receiving residential addiction treatment. Alcohol Alcohol 2016. Online May 5. doi: 10.1093/alcalc/agw025

11 Torrens M, Fonseca F, Mateu G, Farré M. Efficacy of antidepressants in substance use disorders with and without comorbid depression. A systematic review and meta-analysis. Drug Alcohol Depend 2005;78:1–22

12 Hanley GE, Smolina K, Mintzes B, Oberlander TF, Morgan SG. Postpartum hemorrhage and use of serotonin reuptake inhibitor antidepressants in pregnancy. Obstet Gynecol 2016;127:553-61.

13 Hayes RM, Wu P, Shelton RC et al. Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies. Am J Obstet Gynecol 2012;207:49.e1-9.

Competing interests: No competing interests

23 March 2017
alain braillon
senior consultant
University Hospital. 80000 Amiens. France