Risks / Safety of Psychotropic Medication use during Pregnancy
Main Article Content
Keywords
Risks, Safety, Psychotropic Medication, Pregnancy
Abstract
Psychiatric disorders are relatively common among women of childbearing age, who may be prescribed psychotropic drugs. There remains a high level of anxiety regarding their safety among patients and healthcare providers alike, most likely because of the conflicting studies that have been published in the literature and warnings from government organizations. Consequently, treating a psychiatric disorder during pregnancy with pharmacotherapy, is a complex decision making process, which has to be made between the pregnant woman and her health care provider. The objective of this brief review is to discuss the current models for studying the use of drugs in pregnancy and to provide current information on the safety/risk of psychotropic drugs used in pregnancy. The body of evidence in the literature to date suggests that psychotropic drugs as a group are relatively safe to take during pregnancy and women and their health care providers should not be unduly concerned if a woman requires treatment. Optimal control of the psychiatric disorder should be maintained during pregnancy, the post partum period and thereafter. All pregnancies where a mother has a serious psychiatric disorder should be considered high risk and the mother and fetus must be carefully monitored.
References
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2. Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry. 1996 May;153(5):592-606.
3. Einarson TR, Einarson A. Newer antidepressants in pregnancy and rates of major malformations: a meta-analysis of prospective comparative studies. Pharmacoepidemiol Drug Saf 2005 Dec;14(12):823-7.
4. Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM. Use of selective serotonin- reuptake inhibitors in pregnancy and the risk of birth defects. National Birth Defects Prevention Study. N Engl J Med 2007 Jun 28;356(26):2684-92.
5. Louik C, Lin AE, Werler MM, Hernández-Díaz S, Mitchell AA. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007 Jun 28;356(26):2675-83.
6. Ramos E, St -André M, Rey E, Oraichi D, Bérard A. Duration of antidepressant use during pregnancy and risk of major congenital malformations. Br J Psychiatry 2008 May; 192(5):344- 50.
7. Einarson A, Pistelli A, DeSantis M, Malm H, Paulus WD, Panchaud A, Kennedy D, Einarson TR, Koren G. Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry 2008 Jun;165(6):749-52.
8. Lennestål R, Källén B. Delivery outcome in relation to maternal use of some recently introduced antidepressants. J Clin Psychopharmacol 2007 Dec;27(6):607-13.
9. Einarson A, Fatoye B, Sarkar M, Lavigne SV, Brochu J, Chambers C, Mastroiacovo P, Addis A, Matsui D, Schuler L, Einarson TR, Koren G. Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry 2001 Oct;158(10):1728-30. 10. Einarson A, Bonari L, Voyer-Lavigne S, Addis A, Matsui D, Johnson Y, Koren G. A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy. Can J Psychiatry 2003 Mar;48(2):106-10. 11. Chun-Fai-Chan B, Koren G, Fayez I, Kalra S, Voyer-Lavigne S, Boshier A, Shakir S, Einarson A. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol 2005 Mar;192(3):932-6. 12. Cole JA, Modell JG, Haight BR, Cosmatos IS, Stoler JM, Walker AM. Bupropion in pregnancy and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf 2007 May;16(5):474-84.
13. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006 Feb 9;354(6):579-87.
14. 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.
15. 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 Feb; 160:173-6.
16. Maschi S, Clavenna A, Campi R, Schiavetti B, Bernat M, Bonati M. Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study. BJOG 2008 Jan;115(2):283-9.
17. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, Kulin N, Koren G. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997 Jan 23;336(4):258-62.
18. Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002 Nov;159(11):1889-95.
19. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Antenatalexposure to the phenothiazines in relation to congenital malformations, perinatalmortali ty rate, birth weight and intelligence quotient score. Am J Obstet Gynecol 1977;128:486-488.
20. Diav-Citrin O, Shechtman S, Ornoy S, Arnon J, Schaefer C, Garbis H, Clementi M, Ornoy A. Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study. J Clin Psychiatry 2005;66:317-322.
21. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S, Diav-Citrin O, Levinson A, Zipursky RB, Einarson A. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry 2005;66:444-449.
22. Yaeger D, Smith HG, Altshuler LL. Atypical antipsychotics in the treatment ofschizophrenia during pregnancy and the postpartum. Am J Psychiatry 2006 Dec; 163(12):2064-70
23. Coppola D, Russo LJ, Kwarta RF, Jr., Varughese R, Schmider J. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf 2007;30(3):247-64.
24. Newham JJ, Thomas SH, MacRitchie K, McElhatton PR, McAllister-Williams RH. Birthweight of infants after maternal exposure to typical and atypical antipsychotics: prospective comparison study. Br J Psychiatry. 2008 May;192(5):333-7. Erratum in: Br J Psychiatry. 2008 Jun;192(6):477.
25. Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and deliveryoutcome. J Clin Psychopharmacol 2008 Jun;28(3):279-88.
26. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy 1999. Drugs Apr;57(4):535- 44.
27. Wyszynski DF, Nambisan M, Surve T, Alsdorf RM, Smith CR, Holmes LB. Antiepileptic Drug Pregnancy Registry. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 2005 Mar 22;64(6):961-5.
28. Genton P, Semah F, Trinka E. Valproic acid in epilepsy: pregnancy-related issues. Drug Saf. 2006;29(1):1-21.
29. Hol mes LB, Baldwin EJ, Smith CR, Habecker E, Glassman L, Wong SL, Wyszynski DF. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 2008 May 27; 70(22 Pt 2):2152-8.
30. Yerby MS. Clinical care of pregnant women with epilepsy: neural tube defects and folic acid supplementation. Epilepsia 2003; 44 Suppl 3:33-40.
31. Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J. UK Epilepsy and Pregnancy Register. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008 Jul 22;71(4):272-
32. Montouris G. Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav 2003 Jun; 4(3):310-7.
33. Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, Donnenfeld AE, Rieder M, Santelli R, Smythe J. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992 Feb 29; 339(8792):530-3.
34. Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML. A re-evaluation of risk of in utero exposure to lithium. JAMA 1994 Jan 12; 271(2):146-50.
35. Dolovich LR, Addis A, Vaillancourt JM, Power JD, Koren G, Einarson TR. Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and casecontrol studies. BMJ 1998 Sep 26; 317(7162):839-43.
36. Czeizel AE, Rockenbauer M, Sørensen HT, Olsen J. A population-based case-control study of oral chlordiazepoxide use during pregnancy and risk of congenital abnormalities. Neurotoxicol Teratol 2004 Jul-Aug; 26(4):593-8.
37. Wikner BN, Stiller CO, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf 2007 Nov;16(11):1203-10.
38. Diav-Citrin O, Okotore B, Lucarelli K, Koren G. Zopiclone use during pregnancy. Can Fam Physician 2000 Jan; 46:63-4.
2. Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry. 1996 May;153(5):592-606.
3. Einarson TR, Einarson A. Newer antidepressants in pregnancy and rates of major malformations: a meta-analysis of prospective comparative studies. Pharmacoepidemiol Drug Saf 2005 Dec;14(12):823-7.
4. Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM. Use of selective serotonin- reuptake inhibitors in pregnancy and the risk of birth defects. National Birth Defects Prevention Study. N Engl J Med 2007 Jun 28;356(26):2684-92.
5. Louik C, Lin AE, Werler MM, Hernández-Díaz S, Mitchell AA. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007 Jun 28;356(26):2675-83.
6. Ramos E, St -André M, Rey E, Oraichi D, Bérard A. Duration of antidepressant use during pregnancy and risk of major congenital malformations. Br J Psychiatry 2008 May; 192(5):344- 50.
7. Einarson A, Pistelli A, DeSantis M, Malm H, Paulus WD, Panchaud A, Kennedy D, Einarson TR, Koren G. Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry 2008 Jun;165(6):749-52.
8. Lennestål R, Källén B. Delivery outcome in relation to maternal use of some recently introduced antidepressants. J Clin Psychopharmacol 2007 Dec;27(6):607-13.
9. Einarson A, Fatoye B, Sarkar M, Lavigne SV, Brochu J, Chambers C, Mastroiacovo P, Addis A, Matsui D, Schuler L, Einarson TR, Koren G. Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry 2001 Oct;158(10):1728-30. 10. Einarson A, Bonari L, Voyer-Lavigne S, Addis A, Matsui D, Johnson Y, Koren G. A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy. Can J Psychiatry 2003 Mar;48(2):106-10. 11. Chun-Fai-Chan B, Koren G, Fayez I, Kalra S, Voyer-Lavigne S, Boshier A, Shakir S, Einarson A. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol 2005 Mar;192(3):932-6. 12. Cole JA, Modell JG, Haight BR, Cosmatos IS, Stoler JM, Walker AM. Bupropion in pregnancy and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf 2007 May;16(5):474-84.
13. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006 Feb 9;354(6):579-87.
14. 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.
15. 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 Feb; 160:173-6.
16. Maschi S, Clavenna A, Campi R, Schiavetti B, Bernat M, Bonati M. Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study. BJOG 2008 Jan;115(2):283-9.
17. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, Kulin N, Koren G. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997 Jan 23;336(4):258-62.
18. Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002 Nov;159(11):1889-95.
19. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Antenatalexposure to the phenothiazines in relation to congenital malformations, perinatalmortali ty rate, birth weight and intelligence quotient score. Am J Obstet Gynecol 1977;128:486-488.
20. Diav-Citrin O, Shechtman S, Ornoy S, Arnon J, Schaefer C, Garbis H, Clementi M, Ornoy A. Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study. J Clin Psychiatry 2005;66:317-322.
21. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S, Diav-Citrin O, Levinson A, Zipursky RB, Einarson A. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry 2005;66:444-449.
22. Yaeger D, Smith HG, Altshuler LL. Atypical antipsychotics in the treatment ofschizophrenia during pregnancy and the postpartum. Am J Psychiatry 2006 Dec; 163(12):2064-70
23. Coppola D, Russo LJ, Kwarta RF, Jr., Varughese R, Schmider J. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf 2007;30(3):247-64.
24. Newham JJ, Thomas SH, MacRitchie K, McElhatton PR, McAllister-Williams RH. Birthweight of infants after maternal exposure to typical and atypical antipsychotics: prospective comparison study. Br J Psychiatry. 2008 May;192(5):333-7. Erratum in: Br J Psychiatry. 2008 Jun;192(6):477.
25. Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and deliveryoutcome. J Clin Psychopharmacol 2008 Jun;28(3):279-88.
26. Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy 1999. Drugs Apr;57(4):535- 44.
27. Wyszynski DF, Nambisan M, Surve T, Alsdorf RM, Smith CR, Holmes LB. Antiepileptic Drug Pregnancy Registry. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 2005 Mar 22;64(6):961-5.
28. Genton P, Semah F, Trinka E. Valproic acid in epilepsy: pregnancy-related issues. Drug Saf. 2006;29(1):1-21.
29. Hol mes LB, Baldwin EJ, Smith CR, Habecker E, Glassman L, Wong SL, Wyszynski DF. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 2008 May 27; 70(22 Pt 2):2152-8.
30. Yerby MS. Clinical care of pregnant women with epilepsy: neural tube defects and folic acid supplementation. Epilepsia 2003; 44 Suppl 3:33-40.
31. Hunt S, Russell A, Smithson WH, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J, Craig J. UK Epilepsy and Pregnancy Register. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008 Jul 22;71(4):272-
32. Montouris G. Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav 2003 Jun; 4(3):310-7.
33. Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, Donnenfeld AE, Rieder M, Santelli R, Smythe J. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992 Feb 29; 339(8792):530-3.
34. Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML. A re-evaluation of risk of in utero exposure to lithium. JAMA 1994 Jan 12; 271(2):146-50.
35. Dolovich LR, Addis A, Vaillancourt JM, Power JD, Koren G, Einarson TR. Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and casecontrol studies. BMJ 1998 Sep 26; 317(7162):839-43.
36. Czeizel AE, Rockenbauer M, Sørensen HT, Olsen J. A population-based case-control study of oral chlordiazepoxide use during pregnancy and risk of congenital abnormalities. Neurotoxicol Teratol 2004 Jul-Aug; 26(4):593-8.
37. Wikner BN, Stiller CO, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf 2007 Nov;16(11):1203-10.
38. Diav-Citrin O, Okotore B, Lucarelli K, Koren G. Zopiclone use during pregnancy. Can Fam Physician 2000 Jan; 46:63-4.
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Dec 8, 2018
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Einarson, A. (2018). Risks / Safety of Psychotropic Medication use during Pregnancy. Journal of Population Therapeutics and Clinical Pharmacology, 16(1). https://mail.jptcp.com/index.php/jptcp/article/view/291
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How to Cite
Einarson, A. (2018). Risks / Safety of Psychotropic Medication use during Pregnancy. Journal of Population Therapeutics and Clinical Pharmacology, 16(1). https://mail.jptcp.com/index.php/jptcp/article/view/291