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Pregnancy Exposure to Serotonin Reuptake Inhibitors and the Risk of Spontaneous Abortions

Published online by Cambridge University Press:  07 November 2014

Salvatore Gentile
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Abstract

Introduction: A growing number of studies have suggested that maternal exposure to post-tricyclic antidepressants during pregnancy might be associated with an increased risk of poor birth, obstetrical, and neonatal outcomes. Among these complications, the occurrence of spontaneous abortions represents one of the most dramatic events for the pregnant woman.

Methods: The purpose of this study was to review all studies reporting primary data investigating the rate of spontaneous abortions in women treated with selective serotonin reuptake inhibitors during pregnancy. Medical literature information published in English since 1980 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Searches were performed using various combination of search terms and were last updated May 2008. No other limitations were imposed. Twelve articles reporting primary data on the rate of spontaneous abortions in women treated with selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors during early pregnancy outcome of pregnancies exposed to antipsychotics were selected for the review. The author was the only reviewer who performed selection and data extraction.

Results: Information from reviewed studies are scarce and methodologically inadequate to draw definitive conclusions about the hypothesized risk of spontaneous abortions associated with serotoninergic antidepressant exposure during early pregnancy.

Type
Original Research
Information
CNS Spectrums , Volume 13 , Issue 11 , November 2008 , pp. 960 - 966
Copyright
Copyright © Cambridge University Press 2008

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References

REFERENCES

1.Andersson, L, Sundstrom-Poromaa, I, Bixo, M, et al.Point prevalence of psychiatric disorders during the second trimester of pregnancy: a population-based study. Am J Obst Gynecol. 2003;189:148–154.Google Scholar
2.Halbreich, U. Prevalence of mood symptoms and depression during pregnancy: implications for clinical practice and research. CNS Spectr. 2004;9:177–184.CrossRefGoogle ScholarPubMed
3.Weissman, MM, Pilowsky, DJ, Wickramaratne, PG, et al.Remission in maternal depression and child psychopathology. A STAR*D-CHILD report. JAMA. 2006;295:1389–1398.CrossRefGoogle ScholarPubMed
4.Diego, MA, Field, T, Hemandez-Reif, M, Cullen, C, Schanberg, S, Kuhn, C. Prepartum, postpartum, and chronic depression effects on newborns. Psychiatry. 2004;67:63–80.CrossRefGoogle ScholarPubMed
5.Rahman, A, Iqbal, Z, Bunn, J, Lovel, H, Harrington, R. Impact of maternal depression on infant nutritional status and illness: a cohort study. Arch Gen Psychiatry. 2004;61:946–952.CrossRefGoogle ScholarPubMed
6.Oberlander, TF, Warburton, W, Misri, S, Aghajanian, J, Hertzman, C. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor anti-depressants and maternal depression using population-based linked health data. Arch Gen Psychiatry. 2006;63:898–906.Google Scholar
7.Ververs, T, Kaasenbrood, H, Visser, G, Schobben, F, de Jong-van den Berg, L, Egberts, T. Prevalence and patterns of antidepressant drug use during pregnancy. Eur J Clin Pharmacol. 2006;62:863–870.CrossRefGoogle ScholarPubMed
8.Andrade, SE, Raebel, MA, Brown, J, et al.Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol. 2008;198:194.CrossRefGoogle ScholarPubMed
9.Gentile, S. SSRIs in pregnancy and lactation: emphasis on neurodevelopmental outcome. CNS Drugs. 2005;19:622–33.CrossRefGoogle ScholarPubMed
10.Gentile, S. The safety of newer antidepressants in pregnancy and breastfeeding. Drug Saf. 2005;28:137–152.Google Scholar
11.Moses-Kolko, EL, Bogen, D, Perel, D, et al.Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical application. JAMA. 2005;293:2372–2383.Google Scholar
12.Sanz, EJ, De-las Cuevas, C, Kiuru, A, Bate, A, Edwards, R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 2005;365:451–453.Google Scholar
13.Broen, AN, Moum, T, Bodtker, AS, Ekeberg, O. The course of mental health after miscarriage and induced abortion: a longitudinal, five-year follow-up study. BMC Med. 2005;3:18.CrossRefGoogle ScholarPubMed
14.Neugebauer, R. Depressive symptoms at two months after miscarriage: interpreting study findings from an epidemiological versus clinical perspective. Depress Anxiety. 2003;17:152–161.CrossRefGoogle ScholarPubMed
15.Neugebauer, R, Kline, J, Shrout, P, et al.Major depressive disorder in the 6 months after miscarriage. JAMA. 1997;277:383–388.CrossRefGoogle ScholarPubMed
16.Stirtzinger, RM, Robinson, GE, Stewart, DE, Ralevski, E. Parameters of grieving in spontaneous abortion. Int J Psychiatry Med. 1999;29:235–249.CrossRefGoogle ScholarPubMed
17.Klier, CM, Geller, PA, Neugebauer, R. Minor depressive disorder in the context of miscarriage. J Affect Disord. 2000;59:13–21.Google Scholar
18.Geller, PA, Klier, CM, Neugebauer, R. Anxiety disorders following miscarriage. J Clin Psychiatry. 2001;62:432–438.Google Scholar
19.Frost, M, Condon, JT. The psychological sequelae of miscarriage: a critical review of literature. Austr N Z J Psychiatry. 1996;30:54–62.CrossRefGoogle Scholar
20.Pastuszak, A, Schick-Boschetto, B, Zuber, C, et al.Pregnancy outcome following first trimester exposure to fluoxetine (Prozac). JAMA. 1993;269:2246–2248.Google Scholar
21.Chambers, CD, Johnson, KA, Dick, LM, Felix, RJ, Jones, KL. Birth outcomes in pregnant women taking fluoxetine. New Engl J Med. 1996;335:1010–1015.Google Scholar
22.Goldstein, DJ, Corbin, LA, Sundell, KL. Effects of first-trimester fluoxetine exposure on the newborn. Obstet Gynecol. 1997;89:713–718.CrossRefGoogle ScholarPubMed
23.Chambers, CD, Dick, LM, Felix, RJ, Johnson, KA, Jones, KL. Pregnancy outcome in women who use sertraline. Teratology. 1999;59:376.Google Scholar
24.Sivojelezova, A, Shuhaiber, S, Sarkissian, L, Einarson, A, Koren, G. Citalopram use in pregnancy and fetal outcome. Am J Obstet Gynecol. 2005;193:2004–2009.Google Scholar
25.Yaris, F, Kadioglu, M, Kesim, M, et al.Newer antidepressants in pregnancy: prospective outcome of case series. Reproductive Toxicol. 2004;19:235–238.Google Scholar
26.Loebstein, R, Koren, G. Pregnancy outcome and neurodevelopment of children exposed in utero to psychoactive drugs: the Motherisk experience. J Psychiatr Neurosci. 1997;22:192–196.Google Scholar
27.Koren, G, Nulman, I, Addis, A. Outcome of children exposed in utero to fluoxetine: a critical review. Depression Anx. 1998;8:27–31.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
28.Diav-Citrin, O, Shechtman, S, Weinbaun, D, Arnon, J, Wajnberg, R, Ornoy, A. Pregnancy outcome after gestational exposure to paroxetine: a prospective cohort study. Teratology. 2002;65:298.Google Scholar
29.Einarson, A, Fatoye, B, Sarkar, M, et al.Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry. 2001;158:1728–1730.CrossRefGoogle ScholarPubMed
30.McElhatton, PR, Garbis, HM, Elefant, E, et al.The outcomes of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (ENTIS). Repr Toxicol. 1936;10:285–294.Google Scholar
31.Kulin, NA, Pastuszak, A, Sage, SR, et al.Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors. A prospective controlled multicenter study. JAMA. 1998;279:609–610.CrossRefGoogle ScholarPubMed
32.Djulus, J, Koren, G, Einarson, TR, et al.Exposure to mirtazapine during pregnancy: a prospective, comparative study. J Clin Psychiatry. 2006;67:1280–1284.CrossRefGoogle ScholarPubMed
33.Hemels, ME, Einarson, A, Koren, G, Lanctôt, KL, Einarson, TR. Antidepressant use during pregnancy and rates of spontaneous abortion: a meta-analysis. Ann Pharmacother. 2005;39:803–809.CrossRefGoogle ScholarPubMed
34.Rahimi, R, Nifkar, S, Abdoliahi, M. Pregnancy outcomes following exposure to serotonin reuptake inhibitors: a meta-analysis of clinical trials. Repr Toxicol. 2006;22:571–575.Google Scholar
35.Sogiura-Ogasawara, M, Furukawa, TA, Nakano, Y, Hori, S, Aoki, K, Kitamura, T. Depression as potential causal factor in subsequent miscarriage in recurrent spontaneous aborters. Hum Reprod. 2002;17:2580–2584.CrossRefGoogle Scholar
36.García-Enguídanos, A, Valero, A, Luna, S, Domínguez-Rojas, V. Risk factors in miscarriage: a review. Eur J Obstet Gynecol. 2002;102:111–119.Google Scholar
37.Fernandes, O, Sabharwal, M, Smiley, T, Pastuszak, A, Koren, G, Einarson, T. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Repr Toxicol. 1998;12:435–444.CrossRefGoogle ScholarPubMed
38.Hemminki, K, Niemi, ML. Community study of spontaneous abortions: relation to occupation and air pollution by sulfur dioxide, hydrogen sulfide, and carbon disulfide. Int Arch Occup Environ Health. 1982;51:55–63.Google Scholar
39.Risch, HA, Weiss, NS, Clarke, EA, Miller, AB. Risk factors for spontaneous abortion and its recurrence. Am J Epidemiol. 1988;128:420–430.CrossRefGoogle ScholarPubMed
40.Nybo Andersen, AM, Wohlfahrt, J, Christens, P, Olsen, J, Melbye, M. Maternal age and fetal loss: population based register linkage study. BMJ. 2002;320:1708–1712.Google Scholar
41.Kleinhaus, K, Perrin, M, Friedlander, Y, Paltiel, O, Malaspina, D, Harlap, S. Paternal age and spontaneous abortion. Obstet Gynecol. 2006;108:369–377.CrossRefGoogle ScholarPubMed
42.Apgar, BS, Churgay, CA. Spontaneous abortion. Prim Care. 1993;20:621–627.Google Scholar
43. Medline Plus. Miscarriage. Available at: www.nlm.nih.gov/medlineplus/ency/article/001488.htm. Accessed October 2, 2008.Google Scholar
44. Fact sheets. Spontaneous abortion. Health Concerns. Available at: www.emcom.ca/health/abortion.shtml. Accessed October 2, 2008.Google Scholar
45.Negibil, CG, Hickel, P, Messaddeq, N, et al.Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function. Circulation. 2001;103:2973–2979.Google Scholar
46.Louik, C, Lin, AE, Werler, MM, Hernández-Diaz, S, Mitchell, AA. First-trimester use of selective-serotonin reuptake inhibitors and the risk of birth defects. New Engl J Med. 2007;365:2684–2692.Google Scholar
47.Gentile, S, Bellantuono, C. SSRI-exposure during early pregnancy and the risk of fetal major malformations. Focus on paroxetine. J Clin Psychiatry. In press.Google Scholar
48.Alwan, S, Reefhuis, J, Rasmussen, SA, Olney, RS, Friedman, JM. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. New Engl J Med. 2007;365:2675–2683.Google Scholar
49.Gentile, S. SRIs in pregnancy: what happens with the mother [abstract]? Eur Neuropsychopharmacol. 2007;17:341.CrossRefGoogle Scholar
50.Gentile, S. Serotonin reuptake inhibitor-induced perinatal complications. Pediatric Drugs. 2007;9:97–106.Google Scholar
51.Gentile, S. Psychotropic drugs in pregnancy and during breastfeeding. Clinical aspects [abstract]. Eur Psychiatry. 2008;23:373.Google Scholar
52.Oberlander, TF, Warburton, W, Misri, S, Aghajanan, J, Hertzman, C. Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: population-based study. Br J Psychiatry. 2008;192:338–343.Google Scholar
53.Boucher, N, Bairam, A, Beaulac-Baillargeon, L. A new look at the neonate's clinical presentation after in utero exposure to antidepressants in late pregnancy. J Clin Psychopharmacol. 2008;28:334–339.Google Scholar
54.Moses-Kolko, EL, Bogen, D, Perel, J, et al.Neonatal signs after late in utero exposure to serotonin reuptake inhibitors. Literature review and implications for clinical applications. JAMA. 2005;18:2372–2382.CrossRefGoogle Scholar
55.Sanz, EJ, De-las-Cuevas, C, Kiuru, A, Bate, A, Edwards, R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 2005;365:482–487.Google Scholar
56.Källén, B, Otterblad-Olausson, P. Maternal use of selective serotonin reuptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf. 2008;17:801–806.Google Scholar
57.Chambers, CD, Hernandez-Diaz, S, Van Marter, LJ, et al.Selective serotonin reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med. 2006;354:579–587.Google Scholar
58.Gentile, S. Use of escitalopram during pregnancy: navigating towards international guidelines and the real world. Clin Drug Inv. 2008;28:735–739.Google Scholar