Effects adverse of treatment with selective inhibitors of serotonin recaptation on the fetus and neonatals of mothers with gestational depression: A critical review
Keywords:Antidepressants; SSRIs; Risks; Gestational depression; Treatment.
Depression is one of the most common psychiatric disorders, due to the high incidence in this decade, a greater predominance of occurrence in women, among them the major depressive disorder in pregnancy. When the diagnosis is made, the treatment is according to the level of the disease, when it comes to a moderate to severe level, pharmacological treatment with antidepressants begins. Among them, the most prescribed are selective serotonin reuptake inhibitors (SSRIs), they have become first-line drugs of choice because they have a higher safety than the others. However, treatment with SSRIs during pregnancy has implicated several undesirable effects in fetuses and neonates. Therefore, the objective of this study was to investigate the adverse effects on the fetus / neonates of depressive women who underwent drug therapy with SSRIs. This study was characterized in a critical review, using the databases of Pubmed/MEDLINE, Scopus and Web of Science, in which 35 articles were included. After careful analysis of the studies, it was found that SSRI therapy in gestational depression increases the risks to the fetus and neonates for birth defects, such as: cardiac malformation, neonatal abstinence, persistent pulmonary hypertension and possible association with autism spectrum disorder. Therefore, based on scientific evidence, the SSRI drug protocol generates harmful effects on the child, however, the use of antidepressants during pregnancy is often inevitable. Thus, in cases where it may be necessary to use SSRIs, a decision on such a therapeutic approach should be evaluated by analyzing the risks of untreated depression and the risk / benefit ratio of the use of medications.
Abajobir, A. A., Maravilla, J. C., Alati, R., & Najman, J. M. (2016). A systematic review and meta-analysis of the association between unintended pregnancy and perinatal depression. Journal of affective disorders, 192, 56–63. https://doi.org/10.1016/j.jad.2015.12.008.
Alwan, S., Bandoli, G., & Chambers, C. D. (2016). Maternal use of selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. Clinical pharmacology and therapeutics, 100(1), 34–41. https://doi.org/10.1002/cpt.376.
Andalib, S., Emamhadi, M. R., Yousefzadeh-Chabok, S., Shakouri, S. K., Høilund-Carlsen, P. F., Vafaee, M. S., & Michel, T. M. (2017). Maternal SSRI exposure increases the risk of autistic offspring: A meta-analysis and systematic review. European psychiatry : the journal of the Association of European Psychiatrists, 45, 161–166. https://doi.org/10.1016/j.eurpsy.2017.06.001.
Angelotta, C., & Wisner, K. L. (2017). Treating Depression during Pregnancy: Are We Asking the Right Questions?. Birth defects research, 109(12), 879–887. https://doi.org/10.1002/bdr2.1074.
Avram, M. J., Stika, C. S., Rasmussen-Torvik, L. J., Ciolino, J. D., Pinheiro, E., George, A. L., Jr, & Wisner, K. L. (2016). Rationale and design for an investigation to optimize selective serotonin reuptake inhibitor treatment for pregnant women with depression. Clinical pharmacology and therapeutics, 100(1), 31–33. https://doi.org/10.1002/cpt.375.
Bérard, A., Iessa, N., Chaabane, S., Muanda, F. T., Boukhris, T., & Zhao, J. P. (2016). The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis. British journal of clinical pharmacology, 81(4), 589–604. https://doi.org/10.1111/bcp.12849.
Bérard, A., Sheehy, O., Zhao, J. P., Vinet, É., Bernatsky, S., & Abrahamowicz, M. (2017). SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. British Journal of clinical pharmacology, 83(5), 1126–1133. https://doi.org/10.1111/bcp.13194.
Brown, H. K., Hussain-Shamsy, N., Lunsky, Y., Dennis, C. E., & Vigod, S. N. (2017). The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. The Journal of clinical psychiatry, 78(1), e48–e58. https://doi.org/10.4088/JCP.15r10194.
Dubovicky, M., Belovicova, K., Csatlosova, K., & Bogi, E. (2017). Risks of using SSRI / SNRI antidepressants during pregnancy and lactation. Interdisciplinary toxicology, 10(1), 30–34. https://doi.org/10.1515/intox-2017-0004.
Erickson, N. L., Gartstein, M. A., & Dotson, J. (2017). Review of Prenatal Maternal Mental Health and the Development of Infant Temperament. Journal of obstetric, gynecologic, and neonatal nursing : JOGNN, 46(4), 588–600. https://doi.org/10.1016/j.jogn.2017.03.008.
Fava, G. A., Gatti, A., Belaise, C., Guidi, J., & Offidani, E. (2015). Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review. Psychotherapy and psychosomatics, 84(2), 72–81. https://doi.org/10.1159/000370338.
Field T. (2017). Prenatal anxiety effects: A review. Infant behavior & development, 49, 120–128. https://doi.org/10.1016/j.infbeh.2017.08.008.
Forsberg, L., Navér, L., Gustafsson, L. L., & Wide, K. (2014). Neonatal adaptation in infants prenatally exposed to antidepressants--clinical monitoring using Neonatal Abstinence Score. PloS one, 9(11), e111327. https://doi.org/10.1371/journal.pone.0111327.
Furu, K., Kieler, H., Haglund, B., Engeland, A., Selmer, R., Stephansson, O., Valdimarsdottir, U. A., Zoega, H., Artama, M., Gissler, M., Malm, H., & Nørgaard, M. (2015). Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ (Clinical research ed.), 350, h1798. https://doi.org/10.1136/bmj.h1798.
Gentile S. (2015). Prenatal antidepressant exposure and the risk of autism spectrum disorders in children. Are we looking at the fall of Gods?. Journal of affective disorders, 182, 132–137. https://doi.org/10.1016/j.jad.2015.04.048.
Gentile S. (2017). Untreated depression during pregnancy: Short- and long-term effects in offspring. A systematic review. Neuroscience, 342, 154–166. https://doi.org/10.1016/j.neuroscience.2015.09.001.
Grigoriadis, S., VonderPorten, E. H., Mamisashvili, L., Eady, A., Tomlinson, G., Dennis, C. L., Koren, G., Steiner, M., Mousmanis, P., Cheung, A., & Ross, L. E. (2013). The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and meta-analysis. The Journal of clinical psychiatry, 74(4), e309–e320. https://doi.org/10.4088/JCP.12r07967.
Huybrechts, K. F., Hernández-Díaz, S., & Avorn, J. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. The New England journal of medicine, 371(12), 1168–1169. https://doi.org/10.1056/NEJMc1409203.
Kaplan, Y. C., Keskin-Arslan, E., Acar, S., & Sozmen, K. (2016). Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. Reproductive toxicology (Elmsford, N.Y.), 66, 31–43. https://doi.org/10.1016/j.reprotox.2016.09.013.
Kendig, S., Keats, J. P., Hoffman, M. C., Kay, L. B., Miller, E. S., Moore Simas, T. A., Frieder, A., Hackley, B., Indman, P., Raines, C., Semenuk, K., Wisner, K. L., & Lemieux, L. A. (2017). Consensus Bundle on Maternal Mental Health: Perinatal Depression and Anxiety. Obstetrics and gynecology, 129(3), 422–430. https://doi.org/10.1097/AOG.0000000000001902.
Klinger, G., & Merlob, P. (2008). Selective serotonin reuptake inhibitor induced neonatal abstinence syndrome. The Israel journal of psychiatry and related sciences, 45(2), 107–113.
Kobayashi, T., Matsuyama, T., Takeuchi, M., & Ito, S. (2016). Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reproductive toxicology (Elmsford, N.Y.), 65, 170–178. https://doi.org/10.1016/j.reprotox.2016.07.016.
Latendresse, G., Elmore, C., & Deneris, A. (2017). Selective Serotonin Reuptake Inhibitors as First-Line Antidepressant Therapy for Perinatal Depression. Journal of Midwifery & Women’s Health, 62(3), 317-328. https://doi.org/10.1111/jmwh.12607.
Ludke, M. & Andre, M. E. D. A. (2013). Pesquisa em educação: abordagens qualitativas. Ed. EPU.
Malm, H., Artama, M., Gissler, M., & Ritvanen, A. (2011). Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics and gynecology, 118(1), 111–120. https://doi.org/10.1097/AOG.0b013e318220edcc.
Man, K. K., Tong, H. H., Wong, L. Y., Chan, E. W., Simonoff, E., & Wong, I. C. (2015). Exposure to selective serotonin reuptake inhibitors during pregnancy and risk of autism spectrum disorder in children: a systematic review and meta-analysis of observational studies. Neuroscience and biobehavioral reviews, 49, 82–89. https://doi.org/10.1016/j.neubiorev.2014.11.020.
Ornoy, A., & Koren, G. (2018). Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics, drug-drug interactions and adverse effects. Expert opinion on drug metabolism & toxicology, 14(3), 247–259. https://doi.org/10.1080/17425255.2018.1430139.
Oyebode, F., Rastogi, A., Berrisford, G., & Coccia, F. (2012). Psychotropics in pregnancy: safety and other considerations. Pharmacology & therapeutics, 135(1), 71–77. https://doi.org/10.1016/j.pharmthera.2012.03.008.
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. UFSM.https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_Metodologia-Pesquisa-Cientifica.pdf?sequence=1.
Rayen, I., van den Hove, D. L., Prickaerts, J., Steinbusch, H. W., & Pawluski, J. L. (2011). Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence. PloS one, 6(9), e24003. https://doi.org/10.1371/journal.pone.0024003.
Smith K. (2014). Mental health: a world of depression. Nature, 515(7526), 181. https://doi.org/10.1038/515180a.
Tafuri, S., De Pasquale, V., Costagliola, A., Della Morte, R., Avallone, L., & Pavone, L. M. (2017). Health and disease, an orchestra of three players: Serotonin, orexins, and nitric oxide. Journal of neuroscience research, 95(10), 1891–1893. https://doi.org/10.1002/jnr.24030.
Tang, X., Lu, Z., Hu, D., & Zhong, X. (2019). Influencing factors for prenatal Stress, anxiety and depression in early pregnancy among women in Chongqing, China. Journal of affective disorders, 253, 292–302. https://doi.org/10.1016/j.jad.2019.05.003.
Wang, R. Z., Vashistha, V., Kaur, S., & Houchens, N. W. (2016). Serotonin syndrome: Preventing, recognizing, and treating it. Cleveland Clinic journal of medicine, 83(11), 810–817. https://doi.org/10.3949/ccjm.83a.15129.
Wemakor, A., Casson, K., Garne, E., Bakker, M., Addor, M. C., Arriola, L., Gatt, M., Khoshnood, B., Klungsoyr, K., Nelen, V., O'Mahoney, M., Pierini, A., Rissmann, A., Tucker, D., Boyle, B., de Jong-van den Berg, L., & Dolk, H. (2015). Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study.
European journal of epidemiology, 30(11), 1187–1198. https://doi.org/10.1007/s10654-015-0065-y.
Yazdy, M. M., Mitchell, A. A., Louik, C., & Werler, M. M. (2014). Use of selective serotonin-reuptake inhibitors during pregnancy and the risk of clubfoot. Epidemiology (Cambridge, Mass.), 25(6), 859–865. https://doi.org/10.1097/EDE.0000000000000157.
Zemestani, M., & Fazeli Nikoo, Z. (2020). Effectiveness of mindfulness-based cognitive therapy for comorbid depression and anxiety in pregnancy: a randomized controlled trial. Archives of women's mental health, 23(2), 207–214. https://doi.org/10.1007/s00737-019-00962-8.
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Copyright (c) 2021 Thais Pereira Nunes; Larissa Pereira Nunes; Arles Naisa Amaral Silva ; Beatriz Ommati Pirovani; Maria Juliana Sismeiro Dias Morábito ; Leonardo Antônio de Morais; Amanda Scarpin Gruba; Gabriel Pereira Nunes
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