Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes
Abstract
:1. Introduction
1.1. Disorders during Pregnancy
1.1.1. Depression Disorders
1.1.2. Anxiety Disorders
1.1.3. Bipolar Disorder
1.1.4. Sleep Disorders
1.2. Pharmacotherapy
1.2.1. Depression
1.2.2. Anxiety and Obsessive-Compulsive Disorder (OCD)
- 1987—fluoxetine (Prozac): OCD, panic disorder
- 1991—sertraline (Zoloft): OCD, panic disorder, social anxiety disorder
- 1992—paroxetine (Paxil): OCD and panic disorder, social anxiety disorder, generalized anxiety disorder
- 1993—venlafaxine (Effexor): generalized anxiety disorder, panic disorder, social phobia
- 1998—citalopram (Celexa): None
- 2002—escitalopram (Lexapro): Generalized anxiety disorder
1.2.3. Bipolar Disorder
1.2.4. Sleep Disorders
2. Materials and Methods
3. Effects of Maternal Pharmacotherapy on Fetal, Neonatal, and Child Development
3.1. Tri- and Tetracyclics (TCAs) and Monoamine Oxidase Inhibitors (MAOIs)
3.1.1. Fetal and Neonatal Effects: TCAs
3.1.2. Long-Term Developmental Outcomes: TCAs
3.2. Serotonin Reuptake Inhibitors (SRIs)
3.2.1. Fetal and Neonatal Effects: SRIs
3.2.2. Long-Term Developmental Outcomes: SRIs
3.3. Atypical ADs
3.3.1. Fetal and Neonatal Effects: Atypicals
3.3.2. Long-Term Developmental Outcomes: Atypicals
3.4. Conclusions: AD Use during Pregnancy
3.5. Benzodiazepines (BZDs) and Hypnotic Benzodiazepine Receptor Agonists (HBRAs)
3.5.1. Fetal and Neonatal Effects: BZDs and HRBAs
3.5.2. Long-Term Developmental Outcomes: BZDs and HRBAs
3.6. Conclusions—Benzodiazepine Use during Pregnancy
3.7. Beta-Blockers (BBs)
3.7.1. Fetal and Neonatal Effects
3.7.2. Long-Term Developmental Effects: BBs
3.8. Mood Stabilizers: Lithium, Anti-Psychotics and Anti-Epileptics
3.8.1. Fetal and Neonatal Effects
Lithium
Antipsychotics
Antiepileptics (AEDs)
3.8.2. Long-Term Developmental Effects
Lithium
Antipsychotics
Antiepileptics (AEDs)
3.9. Conclusions: Mood Stabilizer Use during Pregnancy
4. Limitations of the Study
5. Conclusions
5.1. Scope of Problem
5.2. Information Sources
5.3. Status of the Literature
6. Future Directions
7. Summary Points
- While the FDA seeks to improve information regarding risk of medication use during pregnancy, there are no clear guidelines regarding the use of ADs during pregnancy.
- Any potential drug-exposure risks to the child must be balanced against the equally risky effects of untreated mental illness or disorder in the mother, especially for serious mood disorders such as major depression and bipolar disorder.
- The results showing adverse effects of maternal mental illness on the child suggest that adequate pharmacotherapy may need to be maintained before, during, and after pregnancy.
- Any additional pregnancy complications would require even closer monitoring of potential drug-related effects due to multiple risk factors related to physiological changes during pregnancy, including changes in circulating levels of hormones, cardiovascular changes, increase in glomerular filtration, postural hypotension, anemia, and increased metabolic rate, and insulin resistance. Management of any disorder during pregnancy should include monitoring of serum drug levels.
- Decisions regarding both medication use and discontinuation during pregnancy should be made carefully, taking full psychiatric history into account, including severity, chronicity, and co-morbidity of the mental illness, disorder, or condition.
- Regarding teratogenicity, it is important to remember that any risk should be compared to the baseline risk of major congenital malformation, which is approximately 2%–4% in the U.S. The same is true for risk of an autism spectrum disorder.
- More rigorous preclinical and clinical retrospective and prospective research is needed to provide better evidence and better inform clinical practice.
Author Contributions
Funding
Conflicts of Interest
References
- World Health Organization. World Medicines Situation. 2011. Available online: https://apps.who.int/iris/bitstream/handle/10665/68735/WHO_EDM_PAR_2004.5.pdf (accessed on 18 June 2019).
- World Health Organization. World Medicines Situation. 2004. Available online: http://apps.who.int/medicinedocs/en/d/Js6160e/ (accessed on 18 June 2019).
- National Center for Health Statistics (US). Health, United States, 2014: With Special Feature on Adults Aged 55–64. Hyattsville (MD): National Center for Health Statistics (US). Available online: https://www.ncbi.nlm.nih.gov/books/NBK299348/ (accessed on 1 Aug 2019).
- Mitchell, A.A.; Gilboa, S.M.; Werler, M.M.; Kelley, K.E.; Louik, C.; Hernandez-Diaz, S. Medication use during pregnancy, with particular focus on prescription drugs: 1976–2008. Am. J. Obstet. Gynecol. 2011, 205, 51. [Google Scholar] [CrossRef] [PubMed]
- Vesga-lópez, O.; Blanco, C.; Keyes, K.; Olfson, M.; Grant, B.F.; Hasin, D.S. Psychiatric disorders in pregnant and postpartum women in the United States. Arch. Gen. Psychiatry 2008, 65, 805–815. [Google Scholar] [CrossRef] [PubMed]
- Hanley, G.E.; Mintzes, B. Patterns of psychotropic medicine use in pregnancy in the United States from 2006 to 2011 among women with private insurance. BMC Preg. Childbirth 2014, 14, 242. [Google Scholar] [CrossRef] [PubMed]
- Kessler, R.C.; Berglund, P.; Demler, O.; Jin, R.; Merikangas, K.R.; Walters, E.E. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 2005, 62, 593–602. [Google Scholar] [CrossRef] [PubMed]
- O’Hara, M.W.; Zekoski, E.M.; Philipps, L.H.; Wright, E.J. Controlled prospective study of postpartum mood disorders: Comparison of childbearing and nonchildbearing women. J. Abnorm. Psychol. 1990, 99, 3–15. [Google Scholar] [CrossRef]
- Altshuler, L.L.; Hendrick, V.; Cohen, L.S. An update on mood and anxiety disorders during pregnancy and the postpartum period. Prim. Care Comp. J. Clin. Psychiatry 2000, 2, 217–222. [Google Scholar] [CrossRef] [PubMed]
- Kumar, R.; Robson, K.M. A prospective study of emotional disorders in childbearing women. Brit. J. Psychiatry 1984, 144, 35–47. [Google Scholar] [CrossRef] [PubMed]
- Teixeira, C.; Figueiredo, B.; Conde, A.; Pacheco, A.; Costa, R. Anxiety and depression during pregnancy in women and men. J. Affect. Disord. 2009, 119, 142–148. [Google Scholar] [CrossRef] [Green Version]
- Rich-Edwards, J.W.; Kleinman, K.; Abrams, A.; Harlow, B.L.; McLaughlin, T.J.; Joffe, H.; Gillman, M.W. Sociodemographic predictors of antenatal and postpartum depressive symptoms among women in a medical group practice. J. Epidemiol. Community Health 2006, 60, 221–227. [Google Scholar] [CrossRef] [Green Version]
- Gotlib, I.H.; Whiffen, V.E.; Wallace, P.M.; Mount, J.H. Prospective investigation of postpartum depression: Factors involved in onset and recovery. J. Abnorm. Psychol. 1991, 100, 122–132. [Google Scholar] [CrossRef]
- Steer, R.A.; Scholl, T.O.; Hediger, M.L.; Fischer, R.L. Self-reported depression and negative pregnancy outcomes. J. Clin. Epidemiol. 1992, 45, 1093–1099. [Google Scholar] [CrossRef]
- Van den Bergh, B.R.H.; van den Heuvel, M.I.; Lahti, M.; Braeken, M.; de Rooij, S.R.; Entringer, S.; Hoyer, D.; Roseboom, T.; Räikkönen, K.; King, S.; et al. Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy. Neurosci. Biobehav. Rev. 2017. [Google Scholar] [CrossRef] [PubMed]
- Bodnar, L.M.; Wisner, K.L.; Moses-Kolko, E.; Sit, D.K.Y.; Hanusa, B.H. Prepregnancy body mass index, gestational weight gain and the likelihood of major depression during pregnancy. J. Clin. Psychiatry 2009, 70, 1290–1296. [Google Scholar] [CrossRef] [PubMed]
- Flynn, H.A.; Chermack, S.T. Prenatal alcohol use: The role of lifetime problems with alcohol, drugs, depression and violence. J. Stud. Alcohol Drugs 2008, 69, 500–509. [Google Scholar] [CrossRef] [PubMed]
- Cripe, S.M.; Frederick, I.O.; Qiu, C.; Williams, M.A. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal comorbid mood and migraine disorders during pregnancy. Paediatric and Perinatal Epidemiology 2011, 25, 116–123. [Google Scholar] [CrossRef] [PubMed]
- Istvan, J. Stress, anxiety, and birth outcomes: A critical review of the evidence. Psychol. Bull. 1986, 100, 331–348. [Google Scholar] [CrossRef]
- Wadhwa, P.D.; Sandman, C.A.; Porto, M.; Dunkel-Schetter, C.; Garite, T.J. The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am. J. Obstet. Gynecol. 1993, 169, 858–865. [Google Scholar] [CrossRef]
- Wisner, K.L.; Zarin, D.A.; Holmboe, E.S.; Appelbaum, P.S.; Gelenberg, A.J.; Leonard, H.L.; Frank, E. Risk-benefit decision making for treatment of depression during pregnancy. Am. J. Psychiatry 2000, 157, 1933–1940. [Google Scholar] [CrossRef]
- Grote, N.K.; Bridge, J.A.; Gavin, A.R.; Melville, J.L.; Iyengar, S.; Katon, W.J. 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, 1012–1024. [Google Scholar] [CrossRef]
- Jablensky, A.V.; Morgan, V.; Zubrick, S.R.; Bower, C.; Yellachich, L.A. Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am. J. Psychiatry 2005, 162, 79–91. [Google Scholar] [CrossRef]
- Chung, E.K.; Mccollum, K.F.; Elo, I.T.; Lee, H.J.; Culhane, J.F. Maternal depressive symptoms and infant health practices among low-income women. Pediatrics 2004, 113, 523–529. [Google Scholar] [CrossRef] [PubMed]
- Lee, H.C.; Lin, H.C. Maternal bipolar disorder increased low birthweight and preterm births: A nationwide population-based study. J. Affect. Dis. 2010, 121, 100–105. [Google Scholar] [CrossRef] [PubMed]
- Bodén, R.; Lundgren, M.; Brandt, L.; Reutfors, J.; Andersen, M.; Kieler, H. Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: Population based cohort study. BMJ 2012, 345, e7085. [Google Scholar] [CrossRef] [PubMed]
- Henin, A.; Biederman, J.; Mick, E.; Sachs, G.S.; Hirschfeld-Becker, D.R.; Sigel, R.S.; Nierenberg, A.A. Psychopathology in the offspring of parents with bipolar disorder: A controlled study. Biological Psychiatry 2005, 58, 554–561. [Google Scholar] [CrossRef] [PubMed]
- Hirshfeld-Becker, D.R.; Biederman, J.; Henin, A.; Faraone, S.V.; Dowd, S.T.; De Petrillo, L.A.; Rosenbaum, J.F. Psychopathology in the young offspring of parents with bipolar disorder: A controlled pilot study. Psychiatry Res. 2006, 145, 155–167. [Google Scholar] [CrossRef] [PubMed]
- Duffy, A.; Alda, M.; Crawford, L.; Milin, R.; Grof, P. The early manifestations of bipolar disorder: A longitudinal prospective study of the offspring of bipolar parents. Bipolar Dis. 2007, 9, 828–838. [Google Scholar] [CrossRef] [PubMed]
- Munk-Olsen, T.; Laursen, T.M.; Mendelson, T.; Pedersen, C.B.; Mors, O.; Mortensen, P.B. Risks and predictors of readmission for a mental disorder during the postpartum period. Arch. Gen. Psychiatry 2009, 66, 189–195. [Google Scholar] [CrossRef]
- Kendell, R.E.; Chalmers, J.C.; Platz, C. Epidemiology of puerperal psychoses. Brit. J. Psychiatry 1987, 150, 662–673. [Google Scholar] [CrossRef]
- Heron, J.; Haque, S.; Oyebode, F.; Craddock, N.; Jones, I. A longitudinal study of hypomania and depression symptoms in pregnancy and the postpartum period. Bipolar Dis. 2009, 11, 410–417. [Google Scholar] [CrossRef]
- Jones, I.; Craddock, N. Bipolar disorder and childbirth: The importance of recognizing risk. Brit. J. Psychiatry 2005, 186, 453–454. [Google Scholar] [CrossRef]
- Akdeniz, F.; Vahip, S.; Pirildar, S.; Vahip, I.; Doganer, I.; Bulut, I. Risk factors associated with childbearing-related episodes in women with bipolar disorder. Psychopathology 2003, 36, 234–238. [Google Scholar] [CrossRef] [PubMed]
- Valdimarsdóttir, U.; Hultman, C.M.; Harlow, B.; Cnattingius, S.; Sparén, P. Psychotic illness in first-time mothers with no previous psychiatric hospitalizations: A population-based study. PLOS Medicine 2009, 6, e13. [Google Scholar] [CrossRef] [PubMed]
- Harlow, B.L.; Vitonis, A.F.; Sparen, P.; Cnattingius, S.; Joffe, H.; Hultman, C.M. Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior prepregnancy or prenatal psychiatric hospitalizations. Arch. Gen. Psychiatry 2007, 64, 42–48. [Google Scholar] [CrossRef] [PubMed]
- Curtis, V. Women are not the same as men: Specific clinical issues for female patients with bipolar disorder. Bipolar Dis. 2005, 7, 16–24. [Google Scholar] [CrossRef] [PubMed]
- Goldstein, B.I.; Levitt, A.J. The specific burden of comorbid anxiety disorders and of substance use disorders in bipolar I disorder. Bipolar Dis. 2008, 10, 67–78. [Google Scholar] [CrossRef] [PubMed]
- Lindahl, V.; Pearson, J.L.; Colpe, L. Prevalence of suicidality during pregnancy and the postpartum. Arch Women’s Mental Health 2005, 8, 77–87. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.H.; Lin, H.C.; Lee, H.C. Pregnancy outcomes among women with panic disorder-do panic attacks during pregnancy matter? J. Affect. Dis. 2010, 120, 258–262. [Google Scholar] [CrossRef] [PubMed]
- Männistö, T.; Mendola, P.; Kiely, M.; O’Loughlin, J.; Werder, E.; Chen, Z.; Grantz, K.L. Maternal psychiatric disorders and risk of preterm birth. Annal. Epidem. 2016, 26, 14–20. [Google Scholar] [CrossRef]
- Wainstock, T.; Lerner-geva, L.; Glasser, S.; Shoham-vardi, I.; Anteby, E.Y. Prenatal stress and risk of spontaneous abortion. Psychosom. Med. 2013, 75, 228–235. [Google Scholar] [CrossRef]
- Mulder, E.J.; Robles de Medina, P.G.; Huizink, A.C.; Van den bergh, B.R.; Buitelaar, J.K.; Visser, G.H. Prenatal maternal stress: Effects on pregnancy and the (unborn) child. Early Hum. Dev. 2002, 70, 3–14. [Google Scholar] [CrossRef]
- Ding, X.X.; Wu, Y.L.; Xu, S.J.; Zhu, R.P.; Jia, X.M.; Zhang, S.F.; Tao, F.B. Maternal anxiety during pregnancy and adverse birth outcomes: A systematic review and meta-analysis of prospective cohort studies. J. Affect. Dis. 2014, 159, 103–110. [Google Scholar] [CrossRef] [PubMed]
- Petzoldt, J.; Wittchen, H.U.; Wittich, J.; Einsle, F.; Höfler, M.; Martini, J. Maternal anxiety disorders predict excessive infant crying: A prospective longitudinal study. Arch. Dis. in Child. 2014, 99, 800–806. [Google Scholar] [CrossRef] [PubMed]
- Van den bergh, B.R.; Marcoen, A. High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds. Child Dev 2004, 75, 1085–1097. [Google Scholar] [CrossRef] [PubMed]
- Van den bergh, B.R.; Mulder, E.J.; Mennes, M.; Glover, V. Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: Links and possible mechanisms. A review. Neurosci. Biobehav. Rev. 2005, 29, 237–258. [Google Scholar] [CrossRef] [PubMed]
- Uguz, F.; Yuksel, G.; Karsidag, C.; Guncu, H.; Konak, M. Birth weight and gestational age in newborns exposed to maternal obsessive-compulsive disorder. Psychiatry Research 2015, 226, 396–398. [Google Scholar] [CrossRef] [PubMed]
- Fairbrother, N.; Janssen, P.; Antony, M.M.; Tucker, E.; Young, A.H. Perinatal anxiety disorder prevalence and incidence. J. Affect. Disord. 2016, 200, 148–155. [Google Scholar] [CrossRef] [Green Version]
- Bandelow, B.; Sojka, F.; Broocks, A.; Hajak, G.; Bleich, S.; Rüther, E. Panic disorder during pregnancy and postpartum period. Eur. Psychiatry 2006, 21, 495–500. [Google Scholar] [CrossRef] [PubMed]
- Forray, A.; Focseneanu, M.; Pittman, B.; Mcdougle, C.J.; Epperson, C.N. Onset and exacerbation of obsessive-compulsive disorder in pregnancy and the postpartum period. J. Clin. Psychiatry 2018, 71, 1061–1068. [Google Scholar] [CrossRef]
- Guglielmi, V.; Vulink, N.C.; Denys, D.; Wang, Y.; Samuels, J.F.; Nestadt, G. Obsessive-compulsive disorder and female reproductive cycle events: Results from the OCD and reproduction collaborative study. Depress. Anxiety 2014, 31, 979–987. [Google Scholar] [CrossRef]
- Kaya, V.; Uguz, F.; Sahingoz, M.; Gezginc, K. Pregnancy-onset obsessive-compulsive disorder: Clinical features, comorbidity, and associated factors. Klin. Psikofarm. Bult. 2015, 25, 248–258. [Google Scholar] [CrossRef]
- Ross, L.E.; Mclean, L.M. Anxiety disorders during pregnancy and the postpartum period: A systematic review. J. Clin. Psychiatry 2006, 67, 1285–1298. [Google Scholar] [CrossRef] [PubMed]
- Grof, P.; Robbins, W.; Alda, M.; Berghoefer, A.; Vojtechovsky, M.; Nilsson, A.; Robertson, C. Protective effect of pregnancy in women with lithium-responsive bipolar disorder. J. Affect. Dis. 2000, 61, 31–39. [Google Scholar] [CrossRef]
- Viguera, A.C.; Tondo, L.; Koukopoulos, A.E.; Reginaldi, D.; Lepri, B.; Baldessarini, R.J. Episodes of mood disorders in 2,252 pregnancies and postpartum periods. Am. J. Psychiatry 2011, 168, 1179–1185. [Google Scholar] [CrossRef] [PubMed]
- Blehar, M.C.; DePaulo, J.R.; Gershon, E.S.; Reich, T.; Simpson, S.G.; Nurnberger, J.I., Jr. Women with bipolar disorder: Findings from the NIMH Genetics Initiative sample. Psychopharm Bull. 1998, 34, 239–243. [Google Scholar]
- Freeman, M.; Smith, K.; Freeman, S.; McElroy, S.; Kmetz, G.; Wright, R.; Keck, P.E., Jr. The impact of reproductive events on the course of bipolar disorder in women. J. Clin. Psychiatry 2002, 63, 284–287. [Google Scholar] [CrossRef] [PubMed]
- Viguera, A.C.; Nonacs, R.; Cohen, L.S.; Tondo, L.; Murray, A.; Baldessarini, R.J. Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am. J. Psychiatry 2000, 157, 179–184. [Google Scholar] [CrossRef]
- Chong, Y.; Fryer, C.D.; Gu, Q. Prescription sleep aid use among adults: United States, 2005–2010. NCHS Data Brief. 2013, 127, 1–8. [Google Scholar]
- Liu, Y.; Wheaton, A.G.; Chapman, D.P.; Cunningham, T.J.; Lu, H.; Croft, J.B. Prevalence of healthy sleep duration among adults—United States, 2014. Morb. Mortal. Wkly. Rep. 2016, 65, 137–141. [Google Scholar] [CrossRef]
- Schoenborn, C.A.; Adams, P.F. Health behaviors of adults: United States, 2005–2007. Vital Health Stat. 2010, 10, 1–132. [Google Scholar]
- Hashmi, A.M.; Bhatia, S.K.; Bhatia, S.K.; Khawaja, I.S. Insomnia during pregnancy: Diagnosis and rational interventions. Pak. J. Med. Sci. 2016, 32, 1030–1037. [Google Scholar] [CrossRef]
- National Sleep Foundation. Women and Sleep: Summary of Findings. 2007. Available online: https://sleepfoundation.org/sites/default/files/Summary_Of_Findings%20-%20FINAL.pdf (accessed on 1 Aug 2019).
- Sedov, I.D.; Cameron, E.E.; Madigan, S.; Tomfohr-Madsen, L.M. Sleep quality during pregnancy: A meta-analysis. Sleep Med. Rev. 2018, 38, 168–176. [Google Scholar] [CrossRef]
- Adewuya, A.O.; Ola, B.A.; Aloba, O.O.; Dada, A.O.; Fasoto, O.O. Prevalence and correlates of depression in late pregnancy among Nigerian women. Depress. Anxiety 2007, 24, 15–21. [Google Scholar] [CrossRef] [PubMed]
- Bansil, P.; Kuklina, E.V.; Meikle, S.F.; Posner, S.F.; Kourtis, A.P.; Ellington, S.R.; Jamieson, D.J. Maternal and fetal outcomes among women with depression. J. Women Health 2010, 19, 329–334. [Google Scholar] [CrossRef] [PubMed]
- Evans, J.; Heron, J.; Francomb, H.; Oke, S.; Golding, J. Cohort study of depressed mood during pregnancy and after childbirth. BMJ 2001, 323, 257–260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wisner, K.L.; Sit, D.K.; Hanusa, B.H.; Moses-Kolko, E.L.; Bogen, D.L.; Hunker, D.F.; Singer, L.T. Major depression and antidepressant treatment: Impact on pregnancy and neonatal outcomes. Am. J. Psychiatry 2009, 166, 557–566. [Google Scholar] [CrossRef] [PubMed]
- Yonkers, K.A.; Vigod, S.; Ross, L.E. Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women. Obs. Gynecol. 2011, 117, 961–977. [Google Scholar] [CrossRef] [PubMed]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; American Psychiatric Publishing: Washington, DC, USA, 2013. [Google Scholar]
- Russell, E.J.; Fawcett, J.M.; Mazmanian, D. Risk of obsessive-compulsive disorder in pregnant and postpartum women: A meta-analysis. J. Clin. Psychiatry 2013, 74, 377–385. [Google Scholar] [CrossRef] [PubMed]
- Morgenthaler, T.I.; Lee-Chiong, T.; Alessi, C.; Friedman, L.; Aurora, N.; Boehlecke, B.; Zak, R. Standards of practice committee of the American Academy of Sleep Medicine: Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep 2007, 30, 1445–1459. [Google Scholar] [CrossRef]
- Reichner, C.A. Insomnia and sleep deficiency in pregnancy. Obstet. Med. 2015, 8, 168–171. [Google Scholar] [CrossRef] [Green Version]
- National Center for Health Statistics. Health, United States, 2010: With Special Feature on Death and Dying. Hyattsville, MD. 2011. Available online: https://www.cdc.gov/nchs/data/hus/hus10.pdf (accessed on 12 September 2019).
- Andrade, S.E.; Gurwitz, J.H.; Davis, R.L.; Chan, K.A.; Finkelstein, J.A.; Fortman, K.; McPhillips, H.; Raebel, M.A.; Roblin, D.; Smith, D.H. Prescription drug use in pregnancy. Am. J. Obs. Gynecol. 2004, 191, 398–407. [Google Scholar] [CrossRef]
- Andrade, S.E.; Raebel, M.A.; Brown, J.; Lane, K.; Livingston, J.; Boudreau, D.; Rolnick, S.J.; Roblin, D.; Smith, D.H.; Willy, M.E.; et al. Use of antidepressant medications during pregnancy: A multisite study. Am. J. Obstet. Gynecol. 2008, 198, 194. [Google Scholar] [CrossRef] [PubMed]
- Oberlander, T.F.; Warburton, W.; Misri, S.; Aghajanian, J.; Hertzman, C. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch. Gen. Psychiatry 2006, 63, 898–906. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. (n.d.); Drugs@FDA: FDA Approved Drug Products. Available online: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (accessed on 18 June 2019).
- Cloos, J.M.; Ferreira, V. Current use of benzodiazepines in anxiety disorders. Curr. Opin. Psychiatry 2009, 22, 90–95. [Google Scholar] [CrossRef] [PubMed]
- Gitlin, M.; Frye, M.A. Maintenance therapies in bipolar disorders. Bipolar Disord. 2012, 14 (Suppl. 2), 51–65. [Google Scholar] [CrossRef] [PubMed]
- Hayes, J.; Prah, P.; Nazareth, I.; King, M.; Walters, K.; Petersen, I.; Osborne, D. Prescribing trends in bipolar disorder: Cohort study in the United Kingdom THIN primary care database 1995–2009. PLoS ONE 2011, 6, e28725. [Google Scholar] [CrossRef]
- Kendall, T. The rise and fall of the atypical antipsychotics. Br. J. Psychiatry 2011, 199, 266–268. [Google Scholar] [CrossRef] [Green Version]
- Hooshmand, F.; Miller, S.; Dore, J.; Wang, P.W.; Hill, S.J.; Portillo, N.; Ketter, T.A. Trends in pharmacotherapy in patients referred to a bipolar specialty clinic, 2000–2011. J. Affect. Disord. 2014, 155, 283–287. [Google Scholar] [CrossRef]
- Kessing, L.V.; Vradi, E.; Andersen, P.K. Nationwide and population-based prescription patterns in bipolar disorder. Bipolar Disord. 2016, 18, 174–182. [Google Scholar] [CrossRef]
- Epstein, R.A.; Bobo, W.V.; Shelton, R.C.; Arbogast, P.G.; Morrow, J.A.; Wang, W.; Chandrasekhar, R.; Cooper, W.O. Increasing use of atypical antipsychotics and anticonvulsants during pregnancy. Pharm. Drug Saf. 2013, 22, 794–801. [Google Scholar] [CrossRef]
- Krawczak, E.M.; Minuzzi, L.; Hidalgo, M.P.; Frey, B.N. Do changes in subjective sleep and biological rhythms predict worsening in postpartum depressive symptoms? A prospective study across the perinatal period. Arch. Womens Ment. Health 2016, 19, 591–598. [Google Scholar] [CrossRef]
- Simpson, W.; Frey, B.N.; Steiner, M. Mild depressive symptoms during the third trimester of pregnancy are associated with disruptions in daily rhythms but not subjective sleep quality. J. Womens Health 2016, 25, 594–598. [Google Scholar] [CrossRef] [PubMed]
- Bush, D.M. Emergency Department Visits Attributed to Overmedication That Involved the Insomnia Medication Zolpidem; Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration: Rockville, MD, USA, 22 May 2014; The CBHSQ Report. [Google Scholar]
- Wikner, B.N.; Stiller, C.O.; Källén, B.; Asker, C. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics. Pharmacoepidemiol Drug Saf. 2007, 16, 988–994. [Google Scholar] [CrossRef] [PubMed]
- Wikner, B.N.; Källén, B. Are hypnotic benzodiazepine receptor agonists teratogenic in humans? J. Clin. Psychopharmacol. 2011, 31, 356–359. [Google Scholar] [CrossRef] [PubMed]
- Ban, L.; West, J.; Gibson, J.E.; Fiaschi, L.; Sokal, R.; Doyle, P.; Tata, L.J. First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study. PLoS ONE 2014, 9, e100996. [Google Scholar] [CrossRef] [PubMed]
- Askaa, B.; Jimenez-Solem, E.; Enghusen Poulsen, H.; Traerup Andersen, J. Maternal Characteristics of Women Exposed to Hypnotic Benzodiazepine Receptor Agonist during Pregnancy. Obstet. Gyn. Int. 2014, 945621. [Google Scholar] [CrossRef] [PubMed]
- Schou, M. What happened later to the lithium babies? a followup study of children born without malformations. Acta Psychiatr. Scand. 1976, 54, 193–197. [Google Scholar] [CrossRef] [PubMed]
- Robson, J.M.; Sullivan, F.M. Serotonin as a Teratogen. BMJ 1964, 5379, 370. [Google Scholar] [CrossRef]
- Crombie, D.L.; Pinsent, R.J.; Fleming, D. Imipramine in pregnancy. BMJ 1972, 1, 745. [Google Scholar] [CrossRef] [PubMed]
- Kuenssberg, E.V.; Knox, J.D. Imipramine in pregnancy. BMJ 1972, 2, 292. [Google Scholar] [CrossRef]
- Sim, M. Imipramine and pregnancy. BMJ 1972, 2, 45. [Google Scholar] [CrossRef]
- Corner, M.A.; Mirmiran, M.; Bour, H.L.; Boer, G.J.; van de Poll, N.E.; van Oyen, H.G.; Uylings, H.B. Does rapid-eye-movement sleep play a role in brain development? Prog. Brain Res. 1980, 53, 347–356. [Google Scholar] [PubMed]
- De Boer, S.; Mirmiran, M.; Van Haaren, F.; Louwerse, A.; van de Poll, N.E. Neurobehavioral teratogenic effects of clomipramine and alpha-methyldopa. Neurotoxicol. Teratol. 1989, 11, 77–84. [Google Scholar] [CrossRef]
- Nikoui, V.; Ostadhadi, S.; Takzare, N.; Nabavi, S.M.-A.; Giorgi, M.; Bakhtiarian, A. The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study. Sci. World J. 2013, 2013, 382434. [Google Scholar] [CrossRef] [PubMed]
- Haller, I.; Lirk, P.; Keller, C.; Wang, G.K.; Gerner, P.; Klimaschewski, L. Differential neurotoxicity of tricyclic antidepressants and novel derivatives in vitro in a dorsal root ganglion cell culture model. Eur. J. Anaesthesiol. 2007, 24, 702–708. [Google Scholar] [CrossRef] [PubMed]
- Maciag, D.; Simpson, K.L.; Coppinger, D.; Lu, Y.; Wang, Y.; Lin, R.C.; Paul, I.A. eonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry. Neuropsychopharmacology 2006, 31, 47–57. [Google Scholar] [CrossRef] [PubMed]
- Idänpään-Heikkilä, J.; Saxén, L. Possible teratogenicity of imipramine-chloropyramine. Lancet 1973, 2, 282–284. [Google Scholar] [CrossRef]
- Rachelefsky, G.S.; Flynt, J.W.; Ebbin, A.J., Jr.; Wilson, M.G.; Banister, P.; Dafoe, C.; Smith, E.S.; Miller, J. Possible teratogenicity of tricyclic antidepressants. Lancet 1972, 1, 838–839. [Google Scholar] [CrossRef]
- Misri, S.; Reebye, P.; Kendrick, K.; Carter, D.; Ryan, D.; Grunau, R.E.; Oberlander, T.F. Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications. Am. J. Psychiatry 2006, 163, 1026–1032. [Google Scholar] [CrossRef]
- Pastuszak, A.; Schick-Boschetto, B.; Zuber, C.; Feldkamp, M.; Pinelli, M.; Sihn, S.; Donnenfeld, A.; McCormack, M.; Leen-Mitchell, M.; Woodland, C.; et al. Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac). JAMA 1993, 269, 2246–2248. [Google Scholar] [CrossRef]
- Lewis-Hall, F.C.; Wilson, M.G.; Tepner, R.G.; Koke, S.C. Fluoxetine vs. tricyclic antidepressants in women with major depressive disorder. J. Womens Health 1997, 6, 337–343. [Google Scholar] [CrossRef]
- Yonkers, K.A.; Wisner, K.L.; Stewart, D.E.; Oberlander, T.F.; Dell, D.L.; Stotland, N.; Ramin, S.; Chaudron, L.; Lockwood, C. The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen. Hosp. Psychiatry 2009, 31, 403–413. [Google Scholar] [CrossRef]
- Gentile, S. Tricyclic antidepressants in pregnancy and puerperium. Expert Opin. Drug Saf. 2014, 13. [Google Scholar] [CrossRef]
- Coyle, I.R. Changes in developing behavior following prenatal administration of imipramine. Pharm. Biochem. Behav. 1975, 3, 799–807. [Google Scholar] [CrossRef]
- Coyle, I.R.; Singer, G. The interaction of post-weaning housing conditions and prenatal drug effects on behaviour. Psychopharmacologia 1975, 41, 237–244. [Google Scholar] [CrossRef] [PubMed]
- Coyle, I.R.; Singer, G. The interactive effects of prenatal imipramine exposure and postnatal rearing conditions on behaviour and histology. Psychopharmacologia 1975, 44, 253–256. [Google Scholar] [CrossRef]
- File, S.E.; Tucker, J.C. Prenatal treatment with clomipramine has an anxiolytic profile in the adolescent rat. Physiol. Behav. 1983, 31, 57–61. [Google Scholar] [CrossRef]
- File, S.E.; Tucker, J.C. Prenatal treatment with clomipramine: Effects on the behaviour of male and female adolescent rats. Psychopharmacologia 1984, 82, 21–224. [Google Scholar] [CrossRef] [PubMed]
- Drago, F.; Continella, G.; Alloro, M.C.; Scapagnini, U. Behavioral effects of perinatal administration of antidepressant drugs in the rat. Neurobehav. Toxicol. Teratol. 1985, 7, 493–497. [Google Scholar]
- Rodríguez Echandía, E.L.; Broitman, S.T. Effect of prenatal and postnatal exposure to therapeutic doses of chlorimipramine on emotionality in the rat. Psychopharmacologia 1983, 79, 236–241. [Google Scholar] [CrossRef]
- Bourke, C.H.; Stowe, Z.N.; Owens, M.J. Prenatal antidepressant exposure: Clinical and preclinical findings. Pharm. Rev. 2014, 66, 435–465. [Google Scholar] [CrossRef]
- Nulman, I.; Rovet, J.; Stewart, D.E.; Wolpin, J.; Gardner, H.A.; Theis, J.G.; Kulin, N.; Koren, G. Neurodevelopment of children exposed in utero to antidepressant drugs. N. Engl. J. Med. 1997, 336, 258–262. [Google Scholar] [CrossRef]
- Wisner, K.L.; Gelenberg, A.J.; Leonard, H.; Zarin, D.; Frank, E. Pharmacologic treatment of depression during pregnancy. JAMA 1999, 282, 1264–1269. [Google Scholar] [CrossRef]
- Nulman, I.; Rovet, J.; Stewart, D.E.; 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, 159, 1889–1895. [Google Scholar] [CrossRef]
- Fornaro, E.; Li, D.; Pan, J.; Belik, J. Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat. Am. J. Respir. Crit. Care Med. 2007, 176, 1035–1040. [Google Scholar] [CrossRef]
- Vorhees, C.V.; Acuff-Smith, K.D.; Schilling, M.A.; Fisher, J.E.; Moran, M.S.; Buelke-Sam, J. A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. Fundam. Appl. Toxicol. 1994, 23, 194–205. [Google Scholar] [CrossRef]
- Noorlander, C.W.; Ververs, F.F.T.; Nikkels, P.G.J.; van Echteld, C.J.A.; Visser, G.H.A.; Smidt, M.P. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE 2008, 3, e2782. [Google Scholar] [CrossRef]
- Byrd, R.A.; Markham, J.K. Developmental toxicology studies of fluoxetine hydrochloride administered orally to rats and rabbits. Fundam. Appl. Toxicol. 1994, 22, 511–518. [Google Scholar] [CrossRef]
- Da Silva, V.A.; Altenburg, S.P.; Malheiros, L.R.; Thomaz, T.G.; Lindsey, C.J. Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy. Braz. J. Med. Biol. Res. 1999, 32, 93–98. [Google Scholar] [CrossRef]
- Bairy, K.L.; Madhyastha, S.; Ashok, K.P.; Bairy, I.; Malini, S. Developmental and behavioral consequences of prenatal fluoxetine. Pharmacology 2007, 79, 1–11. [Google Scholar] [CrossRef]
- Davies, T.S.; Kluwe, W.M. Preclinical toxicological evaluation of sertraline hydrochloride. Drug Chem. Toxicol. 1998, 21, 521–537. [Google Scholar] [CrossRef]
- Haskell, S.E.; Hermann, G.M.; Reinking, B.E.; Volk, K.A.; Peotta, V.A.; Zhu, V.; Roghair, R.D. Sertraline exposure leads to small left heart syndrome in adult mice. Pediatric Res. 2013, 73, 286–293. [Google Scholar] [CrossRef]
- Bauer, S.; Monk, C.; Ansorge, M.; Gyamfi, C.; Myers, M. Impact of antenatal selective serotonin reuptake inhibitor exposure on pregnancy outcomes in mice. Am. J. Obstet. Gynecol. 2010, 203, e371–e374. [Google Scholar] [CrossRef]
- Cabrera, T.M.; Battaglia, G. Delayed decreases in brain 5-hydroxytryptamine2A/2C receptor density and function in male rat progeny following prenatal fluoxetine. J. Pharm. Exp. 1994, 269, 637–645. [Google Scholar]
- Müller, J.C.; Boareto, A.C.; Lourenço, E.L.; Zaia, R.M.; Kienast, M.F.; Spercoski, K.M.; Morais, R.N.; Martino-Andrade, A.J.; Dalsenter, P.R. In utero and lactational exposure to fluoxetine in Wistar rats: Pregnancy outcomes and sexual development. Basic Clin. Pharm. Toxicol. 2013, 113, 132–140. [Google Scholar] [CrossRef]
- Ornoy, A.; Koren, G. SSRIs and SNRIs (SRI) in Pregnancy: Effects on the Course of Pregnancy and the Offspring: How Far Are We from Having All the Answers? Int. J Mol. Sci. 2019, 20, 2370. [Google Scholar] [CrossRef]
- Weisskopf, E.; Fischer, C.J.; Graz, M.B.; Morisod, H.M.; Tolsa, J.F.; Claris, O.; Vial, Y.; Eap, C.B.; Csajka, C.; Panchaud, A. Risk-benefit balance assessment of SSRI antidepressant use during pregnancy and lactation based on best available evidence. Expert Opin. Drug Saf. 2015, 14, 413–427. [Google Scholar] [CrossRef]
- Pedersen, L.H.; Henriksen, T.B.; Vestergaard, M.; Olsen, J.; Bech, B.H. Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: A population based cohort study. Br. Med. J. 2009, 339, b3569. [Google Scholar] [CrossRef]
- Kornum, J.B.; Nielsen, R.B.; Pedersen, L.; Mortensen, P.B.; Norgaard, M. Use of selective serotonin reuptake inhibitors during early pregnancy and the risk of congenital malformations: Updated analysis. Clin. Epidemiol. 2010, 2, 29–36. [Google Scholar] [CrossRef]
- Oberlander, T.F.; Warburton, W.; Misri, S.; Riggs, W.; Aghajanian, J.; Hertzman, C. Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Def. Res. Part. B 2008, 83, 68–76. [Google Scholar] [CrossRef]
- Yazdy, M.M.; Mitchel, A.A.; Louik, C.; Werler, M.M. Use of selective serotonin-reuptake inhibitors during pregnancy and the risk of clubfoot. Epidemiology 2014, 25, 859–865. [Google Scholar] [CrossRef]
- Bérard, A.; Zhao, J.P.; Sheehy, O. Sertraline use during pregnancy and the risk of major malformations. Am. J. Obs. Gynecol. 2015, 212, 795-e1. [Google Scholar] [CrossRef]
- Einarson, A.; Choi, J.; Einarson, T.R.; Koren, G. Adverse effects of antidepressant use in pregnancy: An evaluation of fetal growth and preterm birth. Depress. Anxiety 2010, 27, 35–38. [Google Scholar] [CrossRef]
- El Marroun, H.; Jaddoe, V.W.; Hudziak, J.J.; Roza, S.J.; Steegers, E.A.; Hofman, A.; Verhulst, F.C.; White, T.J.; Stricker, B.H.; Tiemeier, H. Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch. Gen. Psychiatry 2012, 69, 706–714. [Google Scholar] [CrossRef]
- Roca, A.; Garcia-Esteve, L.; Imaz, M.L.; Torres, A.; Hernández, S.; Botet, F.; Gelabert, E.; Subirà, S.; Plaza, A.; Valdés, M.; et al. Obstetrical and neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitors: The relevance of dose. J. Affect. Disord. 2011, 135, 208–215. [Google Scholar] [CrossRef]
- Viktorin, A.; Lichtenstein, P.; Lundholm, C.; Almqvist, C.; D’Onofrio, B.M.; Larsson, H.; Landén, M.; Magnusson, P.K. Selective serotonin re-uptake inhibitor use during pregnancy: Association with offspring birth size and gestational age. Int. J. Epidemiol. 2016, 45, 170–177. [Google Scholar] [CrossRef]
- Sharpley, A.L.; Cowen, P.J. Effect of pharmacologic treatments on the sleep of depressed patients. Biol. Psychiatry 1995, 37, 85–98. [Google Scholar] [CrossRef]
- Trivedi, M.H.; Rush, A.J.; Armitage, R.; Gullion, C.M.; Grannemann, B.D.; Orsulak, P.J.; Roffwarg, H.P. Effects of fluoxetine on the polysomnogram in outpatients with major depression. Neuropsychopharmacology 1999, 20, 447–459. [Google Scholar] [CrossRef]
- Zeskind, P.S.; Stephens, L.E. Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004, 113, 368–375. [Google Scholar] [CrossRef]
- Morrison, J.L.; Riggs, K.W.; Rurak, D.W. Fluoxetine during pregnancy: Impact on fetal development. Reprod. Fertil. Dev. 2005, 17, 641–650. [Google Scholar] [CrossRef]
- Oberlander, T.F.; Eckstein, G.R.; Fitzgerald, C.; Ellwood, A.L.; Misri, S.; Rurak, D.; Riggs, K.W. Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr. Res. 2002, 51, 443–453. [Google Scholar] [CrossRef]
- Oberlander, T.F.; Grunau, R.E.; Fitzgerald, C.; Papsdorf, M.; Rurak, D.; Riggs, W. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 2005, 115, 411–425. [Google Scholar] [CrossRef]
- Oberlander, T.F.; Reebye, P.; Misri, S.; Papsdorf, M.; Kim, J.; Grunau, R.E. Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy. Arch. Pediatr. Adolesc. Med. 2007, 161, 22–29. [Google Scholar] [CrossRef]
- Oberlander, T.F.; Grunau, R.; Mayes, L.; Riggs, W.; Rurak, D.; Papsdorf, M.; Misri, S.; Weinberg, J. Hypothalamic-pituitary-adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure. Early Hum. Dev. 2008, 84, 689–697. [Google Scholar] [CrossRef]
- Oberlander, T.F.; Papsdorf, M.; Brain, U.M.; Misri, S.; Ross, C.; Grunau, R.E. Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age. Arch. Pediatr. Adolesc. Med. 2010, 164, 444–451. [Google Scholar] [CrossRef]
- Rampono, J.; Simmer, K.; Ilett, K.F.; Hackett, L.P.; Doherty, D.A.; Elliot, R.; Kok, C.H.; Coenen, A.; Forman, T. lacental transfer of SSRI and SNRI antidepressants and effects on the neonate. Pharmacopsychiatry 2009, 42, 95–100. [Google Scholar] [CrossRef]
- Grigoriadis, S.; VonderPorten, E.H.; Mamisashvili, L.; Eady, A.; Tomlinson, G.; Dennis, C.L.; Koren, G.; Steiner, M.; Mousmanis, P.; Cheung, A.; et al. The effect of prenatal antidepressant exposure on neonatal adaptation: A systematic review and meta-analysis. J. Clin. Psychiatry 2013, 74, e309–e320. [Google Scholar] [CrossRef]
- Kiryanova, V.; McAllister, B.B.; Dyck, R.H. Long-term outcomes of developmental exposure to fluoxetine: A review of the animal literature. Dev. Neurosci. 2013, 35, 437–439. [Google Scholar] [CrossRef]
- Casper, R.C.; Fleisher, B.E.; Lee-Ancajas, J.C.; Gillis, A.; Gaylor, E.; DeBattista, A.; Hoyme, H.E. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J. Pediatr. 2003, 142, 402–408. [Google Scholar] [CrossRef] [Green Version]
- Malm, H.; Brown, A.S.; Gissler, M.; Gyllenberg, D.; Hinkka-Yli-Salomäki, S.; McKeague, I.W.; Weissman, M.; Wickramaratne, P.; Artama, M.; Gingrich, J.A.; et al. Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: A national register-based study. J. Am. Acad. Child. Adolesc. Psychiatry 2016, 55, 359–366. [Google Scholar] [CrossRef]
- Croen, L.A.; Grether, J.K.; Yoshida, C.K.; Odouli, R.; Hendrick, V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch. Gen. Psychiatry 2011, 68, 1104–1112. [Google Scholar] [CrossRef]
- Boukhris, T.; Sheehy, O.; Mottron, L.; Bérard, A. Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatr. 2016, 170, 117–124. [Google Scholar] [CrossRef]
- Rai, D.; Lee, B.K.; Dalman, C.; Golding, J.; Lewis, G.; Magnusson, C. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: Population based case-control study. BMJ 2013, 346, f2059. [Google Scholar] [CrossRef]
- Gentile, S. Prenatal antidepressant exposure and the risk of autism spectrum disorders in children. Are we looking at the fall of Gods? J. Affect. Disord. 2015, 182, 132–137. [Google Scholar] [CrossRef]
- Man, K.K.; Tong, H.H.; Wong, L.Y.; Chan, E.W.; Simonoff, E.; Wong, I.C. 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. Neurosci. Biobehav. Rev. 2015, 49, 82–89. [Google Scholar] [CrossRef] [Green Version]
- Hsiao, S.Y.; Cherng, C.F.; Yang, Y.K.; Yeh, T.L.; Yu, L. Prenatal bupropion exposure enhances the cocaine reward and stress susceptibility in adult mice. Chin. J. Physiol. 2005, 48, 223–229. [Google Scholar]
- Su, S.W.; Cherng, C.F.; Lin, Y.C.; Yu, L. Prenatal exposure of bupropion may enhance agitation, anxiety responses, and sensitivity to cocaine effects in adult mice. Chin. J. Physiol. 2007, 50, 1–8. [Google Scholar]
- De Long, N.; Hyslop, J.R.; Nicholson, C.J.; Morrison, K.M.; Gerstein, H.C.; Holloway, A.C. Postnatal metabolic and reproductive consequences of fetal and neonatal exposure to the smoking cessation drug bupropion. Reprod. Sci. 2013, 20, 1156–1161. [Google Scholar] [CrossRef]
- Manakova, E.; Hubickova, L. Antidepressant drug exposure during pregnancy. CZTIS small prospective study. Neuro. Endocrinol. Lett. 2011, 32 (Suppl. 1), 53–56. [Google Scholar]
- Einarson, A.; Choi, J.; Einarson, T.R.; Koren, G. Incidence of major malformations in infants following antidepressant exposure in pregnancy: Results of a large prospective cohort study. Can. J. Psychiatry 2009, 54, 242–246. [Google Scholar] [CrossRef]
- Ross, L.E.; Grigoriadis, S.; Mamisashvili, L.; Vonderporten, E.H.; Roerecke, M.; Rehm, J.; Dennis, C.L.; Koren, G.; Steiner, M.; Mousmanis, P.; et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: A systematic review and meta-analysis. JAMA Psychiatry 2013, 70, 436–443. [Google Scholar] [CrossRef]
- Huang, H.; Coleman, S.; Bridge, J.A.; Yonkers, K.; Katon, W. A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen. Hosp. Psychiatry 2014, 36, 13–18. [Google Scholar] [CrossRef]
- Rodriguez-Porcel, F.; Green, D.; Khatri, N.; Harris, S.S.; May, W.L.; Lin, R.C.; Paul, I.A. eonatal exposure of rats to antidepressants affects behavioral reactions to novelty and social interactions in a manner analogous to autistic spectrum disorders. Anat. Rec. 2011, 294, 1726–1735. [Google Scholar] [CrossRef]
- Sahoo, J.; Pattnaik, A.K.; Mishra, N. Behavioral and developmental changes in rats with prenatal exposure of mirtazapine. Sci. Pharm. 2010, 78, 451–463. [Google Scholar] [CrossRef]
- Suri, R.; Lin, A.S.; Cohen, L.S.; Altshuler, L.L. Acute and long-term behavioral outcome of infants and children exposed in utero to either maternal depression or antidepressants: A review of the literature. J. Clin. Psychiatry 2014, 75, e1142–e1152. [Google Scholar] [CrossRef]
- Simoncelli, M.; Martin, B.Z.; Bérard, A. Antidepressant use during pregnancy: A critical systematic review of the literature. Curr. Drug Saf. 2010, 5, 153–170. [Google Scholar] [CrossRef]
- Udechuku, A.; Nguyen, T.; Hill, R.; Szego, K. Antidepressants in pregnancy: A systematic review. Aust. N. Z. J. Psychiatry 2010, 44, 967–996. [Google Scholar]
- Tucker, J.C. Benzodiazepines and the developing rat: A critical review. Neurosci. Biobehav. Rev. 1985, 9, 101–111. [Google Scholar] [CrossRef]
- Bellantuono, C.; Tofani, S.; Di Sciascio, G.; Santone, G. Benzodiazepine exposure in pregnancy and risk of major malformations: A critical overview. Gen. Hosp. Psychiatry 2013, 35, 3–8. [Google Scholar] [CrossRef]
- Calderon-Margalit, R.; Qiu, C.; Ornoy, A.; Siscovick, D.S.; Williams, M.A. Risk of preterm delivery and other adverse perinatal outcomes in relation to maternal use of psychotropic medications during pregnancy. Am. J. Obs. Gynecol. 2009, 201, e1–e8. [Google Scholar] [CrossRef]
- Enato, E.; Moretti, M.; Koren, G. The fetal safety of benzodiazepines: An updated meta-analysis. J. Obs. Gynaecol. Can. 2011, 33, 46–48. [Google Scholar] [CrossRef]
- Iqbal, M.M.; Sobhan, T.; Ryals, T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatr. Serv. 2002, 53, 39–49. [Google Scholar] [CrossRef]
- Depoortere, H.; Zivkovic, B.; Lloyd, K.G.; Sanger, D.J.; Perrault, G.; Langer, S.Z. Bartholini, G. Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects. J. Pharm. Exp. 1986, 237, 649–658. [Google Scholar]
- Langtry, H.D.; Benfield, P. Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs 1990, 40, 291–313. [Google Scholar] [CrossRef]
- Roberts, A.A.; Kellogg, C.K. Synchronous postnatal increase in α1 and γ2L GABAA receptor mRNAs and high affinity zolpidem binding across three regions of rat brain. Brain Res. Dev. Brain Res. 2000, 119, 21–32. [Google Scholar] [CrossRef]
- Cannizzaro, C.; Cannizzaro, E.; Gagliano, M.; Mangiapane, N. Behavioural responsiveness to picrotoxin and desipramine in adult rats prenatally exposed to different benzodiazepine receptor agonists. Eur. Neuropsychopharmacol. 1995, 5, 523–526. [Google Scholar] [CrossRef]
- File, S.E. Effects of neonatal administration of diazepam and lorazepam on performance of adolescent rats in tests of anxiety, aggression, learning and convulsions. Neurobehav. Toxicol. Teratol. 1986, 8, 301–306. [Google Scholar]
- File, S.E. The effects of neonatal administration of clonazepam on passive avoidance and on social, aggressive and exploratory behavior of adolescent male rats. Neurobehav. Toxicol. Teratol. 1986, 8, 447–452. [Google Scholar]
- File, S.E. Behavioral changes persisting into adulthood after neonatal benzodiazepine administration in the rat. Neurobehav. Toxicol. Teratol. 1986, 8, 453–461. [Google Scholar]
- File, S.E. Diazepam and caffeine administration during the first week of life: Changes in neonatal and adolescent behavior. Neurotoxicol. Teratol. 1987, 9, 9–16. [Google Scholar] [CrossRef]
- Schroeder, H.; Humbert, A.C.; Desor, D.; Nehlig, A. Long-term consequences of neonatal exposure to diazepam on cerebral glucose utilization, learning, memory and anxiety. Brain Res. 1997, 766, 142–152. [Google Scholar] [CrossRef]
- Nicosia, A.; Giardina, L.; Di Leo, F.; Medico, M.; Mazzola, C.; Genazzani, A.A.; Drago, F. Long-lasting behavioral changes induced by pre- or neonatal exposure to diazepam in rats. Eur. J. Pharmacol. 2003, 469, 103–109. [Google Scholar] [CrossRef]
- El Marroun, H.; White, T.; Verhulst, F.C.; Tiemeier, H. Maternal use of antidepressant or anxiolytic medication during pregnancy and childhood neurodevelopmental outcomes: A systematic review. Eur. Child. Adolesc. Psychiatry 2014, 23, 973–992. [Google Scholar] [CrossRef]
- Juric, S.; Newport, D.J.; Ritchie, J.C.; Galanti, M.; Stowe, Z.N. Zolpidem (Ambien) in pregnancy: Placental passage and outcome. Arch. Womens Ment. Health 2009, 12, 441–446. [Google Scholar]
- Askew, J.P. Zolpidem. Addiction in a pregnant woman with a history of second-trimester bleeding. Pharmacother 2007, 27, 306–308. [Google Scholar] [CrossRef]
- Wang, L.H.; Lin, H.C.; Lin, C.C.; Chen, Y.H.; Lin, H.C. Increased risk of adverse pregnancy outcomes in women receiving zolpidem during pregnancy. Clin. Pharm. 2010, 88, 369–374. [Google Scholar] [CrossRef]
- Sharma, A.; Sayeed, N.; Khees, C.R.; Akhtar, S. High dose zolpidem induced fetal neural tube defects. Curr. Drug Saf. 2011, 6, 128–129. [Google Scholar]
- Odsbu, I.; Skurtveit, S.; Selmer, R.; Roth, C.; Hernandez-diaz, S.; Handal, M. Prenatal exposure to anxiolytics and hypnotics and language competence at 3 years of age. Eur. J. Clin. Pharm. 2015, 71, 283–291. [Google Scholar] [CrossRef]
- Kieviet, N.; Dolman, K.M.; Honig, A. The use of psychotropic medication during pregnancy: How about the newborn? Neuropsychiatr. Dis. Treat. 2013, 9, 1257–1266. [Google Scholar] [CrossRef]
- Tomfohr-Madsen, L.M.; Clayborne, Z.M.; Rouleau, C.R.; Campbell, T.S. Sleeping for Two: An open-pilot study of cognitive behavioral therapy for insomnia in pregnancy. Behav. Sleep Med. 2016, 28, 1–17. [Google Scholar]
- Xie, R.; Guo, Y.; Krewski, D.; Mattison, D.; Walker, M.C.; Nerenberg, K.; Wen, S.W. Beta blockers increase the risk of being born small for gestational age or of being institutionalized during infancy. BJOG 2014, 121, 1090–1096. [Google Scholar] [CrossRef]
- Tabacova, S.; Kimmel, C.A.; Wall, K.; Hansen, D. Atenolol developmental toxicity: Animal-to-human comparisons. Birth Defects 2003, 67, 181–192. [Google Scholar] [CrossRef]
- Podymow, T.; August, P. Update on the use of antihypertensive drugs in pregnancy. Hypertens 2008, 51, 960–969. [Google Scholar] [CrossRef]
- Ersbøll, A.S.; Hedegaard, M.; Søndergaard, B.; Ersbøll, M.; Johansen, M. Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction. BJOG 2014, 121, 618–626. [Google Scholar] [CrossRef] [Green Version]
- Butters, L.; Kennedy, S.; Rubin, P.C. Atenolol in essential hypertension during pregnancy. BMJ 1990, 301, 587–589. [Google Scholar] [CrossRef]
- Lip, G.Y.H.; Beevers, M.; Churchill, D.; Shaffer, L.M.; Beevers, D.G. Effect of atenolol on birth weight. Am. J. Cardiol. 1997, 79, 1436–1438. [Google Scholar] [CrossRef]
- Magee, L.A. Drugs in pregnancy: Antihypertensives. Best. Pr. Res. Clin. Obs. Gynaecol. 2001, 15, 827–845. [Google Scholar] [CrossRef]
- Tanaka, K.; Tanaka, H.; Kamiya, C.; Katsuragi, S.; Sawada, M.; Tsuritani, M.; Yoshida, M.; Iwanaga, N.; Yoshimatsu, J.; Ikeda, T. Beta-blockers and fetal growth restriction in pregnant women with cardiovascular disease. Circ. J. 2016, 80, 2221–2226. [Google Scholar] [CrossRef]
- Bayliss, H.; Churchill, D.; Beevers, M.; Beevers, D.G. Antihypertensive drugs in pregnancy and fetal growth: Evidence for “pharmacological programming” in the first trimester? Hypertens. Pregnancy 2002, 21, 161–174. [Google Scholar] [CrossRef]
- Montan, S.; Ingemarsson, I.; Marsál, K.; Sjöberg, N.O. Randomised controlled trial of atenolol and pindolol in human pregnancy: Effects on fetal haemodynamics. BMJ 1992, 304, 946–949. [Google Scholar] [CrossRef]
- Lydakis, C.; Lip, G.Y.H.; Beevers, M.; Beevers, D.G. Atenolol and fetal growth in pregnancies complicated by hypertension. Am. J. Hypertens. 1999, 12, 541–547. [Google Scholar] [CrossRef]
- Lennestål, R.; Olausson, P.O.; Källén, B. Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants. Eur. J. Clin. Pharm. 2009, 65, 615–625. [Google Scholar] [CrossRef] [Green Version]
- Cooper, W.O.; Hernandez-Diaz, S.; Arbogast, P.G.; Dudley, J.A.; Dyer, S.; Gideon, P.S.; Hall, K.; Ray, W.A. Major congenital formations after first-trimester exposure to ACE inhibitors. N. Engl. J. Med. 2006, 354, 2443–2451. [Google Scholar] [CrossRef]
- Waterman, E.J.; Magee, L.A.; Lim, K.I.; Skoll, A.; Rurak, D.; von Dadelszen, P. Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review. Hypertens. Pregnancy 2004, 23, 155–169. [Google Scholar] [CrossRef]
- Davis, R.L.; Eastman, D.; McPhillips, H.; Raebel, M.A.; Andrade, S.E.; Smith, D.; Yood, M.U.; Dublin, S.; Platt, R. Risks of congential malformations and perinatal events among infants exposed to calcium channel and beta-blockers during pregnancy. Pharm. Drug Saf. 2011, 20, 138–145. [Google Scholar]
- Ryan, C.L.; Pappas, B.A. Prenatal exposure to antiadrenergic antihypertensive drugs: Effects on neurobehavioral development and the behavioral consequences of enriched rearing. Neurotoxicol. Teratol. 1990, 12, 359–366. [Google Scholar] [CrossRef]
- Reynolds, B.; Butters, L.; Evans, J.; Adams, T.; Rubin, P.C. First year of life after the use of atenolol in pregnancy. Arch. Dis. Child. 1984, 59, 1061–1063. [Google Scholar] [CrossRef]
- Sharma, A.; Rawat, A.K. Teratogenic effects of lithium and ethanol in the developing fetus. Alcohol 1986, 3, 101–106. [Google Scholar] [CrossRef]
- Marathe, M.R.; Thomas, G.P. Embryotoxicity and teratogenicity of lithium carbonate in Wistar rat. Toxicol. Lett. 1986, 34, 115–120. [Google Scholar] [CrossRef]
- Giles, J.J.; Bannigan, J.G. Teratogenic and developmental effects of lithium. Curr. Pharm. Des. 2006, 12, 1531–1541. [Google Scholar] [CrossRef]
- Edmonds, L.D.; Oakley, G.P. Ebstein’s anomaly and maternal lithium exposure during pregnancy. Teratology 1990, 41, 551–552. [Google Scholar]
- Jacobson, S.J.; Jones, K.; Johnson, K.; Ceolin, L.; Kaur, P.; Sahn, D.; Donnenfeld, A.E.; Rieder, M.; Santelli, R.; Smythe, J.; et al. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet 1992, 339, 530–533. [Google Scholar] [CrossRef]
- Cohen, L.S.; Friedman, J.M.; Jefferson, J.W.; Johnson, E.M.; Weiner, M.L. A reevaluation of risk of in utero exposure to lithium. JAMA 1994, 271, 146–150. [Google Scholar] [CrossRef] [PubMed]
- Yacobi, S.; Ornoy, A. Is lithium a real teratogen? What can we conclude from the prospective versus retrospective studies? A review. Isr. J. Psychiatry Relat. Sci. 2008, 45, 95–106. [Google Scholar] [PubMed]
- Schou, M.; Goldfield, M.D.; Weinstein, M.R.; Villeneuve, A. Lithium and pregnancy. I. Report from the Register of Lithium Babies. Br. Med. J. 1973, 2, 135–136. [Google Scholar] [CrossRef] [PubMed]
- Kozma, C. Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature. Am. J. Med. Genet. Part. A 2005, 132, 441–444. [Google Scholar] [CrossRef]
- Llewellyn, A.; Stowe, Z.N.; Strader, J.R., Jr. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. J. Clin. Psychiatry 1998, 59 (Suppl. 6), 57–64. [Google Scholar]
- Simard, M.; Gumbiner, B.; Lee, A.; Lewis, H.; Norman, D. Lithium carbonate intoxication. A case report and review of the literature. Arch. Intern. Med. 1989, 149, 36–46. [Google Scholar] [CrossRef] [PubMed]
- Messiha, F.S. Lithium and the neonate: Developmental and metabolic aspects. Alcohol 1986, 3, 107–112. [Google Scholar] [CrossRef]
- Luo, J. Lithium-mediated protection against ethanol neurotoxicity. Front. Neurosci. 2010, 4, 41. [Google Scholar] [CrossRef]
- De Ferrari, G.V.; Chacón, M.A.; Barría, M.I.; Garrido, J.L.; Godoy, J.A.; Olivares, G.; Reyes, A.E.; Alvarez, A.; Bronfman, M.; Inestrosa, N.C. Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by beta-amyloid fibrils. Mol. Psychiatry 2003, 8, 195–208. [Google Scholar] [CrossRef]
- Senatorov, V.V.; Ren, M.; Kanai, H.; Wei, H.; Chuang, D.M. Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington’s disease. Mol. Psychiatry 2004, 9, 371–385. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Li, Q.; Du, X.; Sun, Y.; Wang, X.; Kroemer, G.; Blomgren, K.; Zhu, C. Lithium-mediated long-term neuroprotection in neonatal rat hypoxia-ischemia is associated with antiinflammatory effects and enhanced proliferation and survival of neural stem/progenitor cells. J. Cereb. Blood Flow Metab. 2011, 31, 2106–2115. [Google Scholar] [CrossRef] [PubMed]
- Shin, W.J.; Gwak, M.; Baek, C.H.; Kim, K.S.; Park, P.H. Neuroprotective effects of lithium treatment following hypoxic-ischemic brain injury in neonatal rats. Childs Nerv. Syst. 2012, 28, 191–198. [Google Scholar] [CrossRef] [PubMed]
- Guo, W.; Allan, A.M.; Zong, R.; Zhang, L.; Johnson, E.B.; Schaller, E.G.; Murthy, A.C.; Goggin, S.L.; Eisch, A.J.; Oostra, B.A.; et al. Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nat. Med. 2011, 17, 559–565. [Google Scholar] [CrossRef] [PubMed]
- Bianchi, P.; Ciani, E.; Contestabile, A.; Guidi, S.; Bartesaghi, R. Lithium restores neurogenesis in the subventricular zone of the Ts65Dn mouse, a model for Down syndrome. Brain Pathol. 2010, 20, 106–118. [Google Scholar] [CrossRef] [PubMed]
- Contestabile, A.; Greco, B.; Ghezzi, D.; Tucci, V.; Benfenati, F.; Gasparini, L. Lithium rescues synaptic plasticity and memory in Down syndrome mice. J. Clin. Investig. 2013, 123, 348–361. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.; Bai, Y.; Tan, T.; Li, H.; Xia, S.; Chang, X.; Zhou, Z.; Zhou, W.; Li, T.; Wang, Y.T.; et al. Lithium ameliorates autistic-like behaviors induced by neonatal isolation in rats. Front. Behav. Neurosci. 2014, 8, 234. [Google Scholar] [CrossRef] [PubMed]
- Wlodarczyk, B.J.; Ogle, K.; Lin, L.Y.; Bialer, M.; Finnell, R.H. Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine in mice. Bipolar Disord. 2015, 17, 615–625. [Google Scholar] [CrossRef]
- Singh, K.P.; Tripathi, N. Prenatal exposure of a novel antipsychotic aripiprazole: Impact on maternal, fetal and postnatal body weight modulation in rats. Curr. Drug Saf. 2014, 9, 43–48. [Google Scholar] [CrossRef]
- Singh, K.P.; Tripathi, N. Prenatal exposure to a novel antipsychotic quetiapine: Impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats. Int. J. Dev. Neurosci. 2015, 42, 59–67. [Google Scholar] [CrossRef]
- Lin, H.C.; Chen, I.J.; Chen, Y.H.; Lee, H.C.; Wu, F.J. Maternal schizophrenia and pregnancy outcome: Does the use of antipsychotics make a difference? Schizophr. Res. 2010, 116, 55–60. [Google Scholar] [CrossRef] [PubMed]
- Newham, J.J.; Thomas, S.H.; MacRitchie, K.; McElhatton, P.R.; McAllister-Williams, R.H. Birth weight of infants after maternal exposure to typical and atypical antipsychotics: Prospective comparison study. Br. J. Psychiatry 2008, 192, 333–337. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Newport, D.J.; Calamaras, M.R.; DeVane, C.L.; Donovan, J.; Beach, A.J.; Winn, S.; Knight, B.T.; Gibson, B.B.; Viguera, A.C.; Owens, M.J.; et al. Atypical antipsychotic administration during late pregnancy: Placental passage and obstetrical outcomes. Am. J. Psychiatry 2007, 164, 1214–1220. [Google Scholar] [CrossRef] [PubMed]
- Reis, M.; Källén, B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J. Clin. Psychopharmacol. 2008, 28, 279–288. [Google Scholar] [CrossRef] [PubMed]
- Bodén, R.; Lundgren, M.; Brandt, L.; Reutfors, J.; Kieler, H. Antipsychotics during pregnancy: Relation to fetal and maternal metabolic effects. Arch. Gen. Psychiatry 2012, 69, 715–721. [Google Scholar] [CrossRef] [PubMed]
- Petersen, I.; McCrea, R.L.; Sammon, C.J.; Osborn, D.P.; Evans, S.J.; Cowen, P.J.; Freemantle, N.; Nazareth, I. Risks and benefits of psychotropic medication in pregnancy: Cohort studies based on UK electronic primary care health records. Health Technol. Assess. 2016, 20, 1–176. [Google Scholar] [CrossRef] [PubMed]
- Coughlin, C.G.; Blackwell, K.A.; Bartley, C.; Hay, M.; Yonkers, K.A.; Bloch, M.H. Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy. Obs. Gynecol. 2015, 125, 1224–1235. [Google Scholar] [CrossRef]
- Fisher, J.E.; Vorhees, C.V. Developmental toxicity of antiepileptic drugs: Relationship to postnatal dysfunction. Pharm. Res. 1992, 26, 207–221. [Google Scholar] [CrossRef]
- Meador, K.J.; Baker, G.; Cohen, M.J.; Gaily, E.; Westerveld, M. Cognitive/behavioral teratogenetic effects of antiepileptic drugs. Epilepsy Behav. 2007, 11, 292–302. [Google Scholar] [CrossRef] [Green Version]
- Bittigau, P.; Sifringer, M.; Genz, K.; Reith, E.; Pospischil, D.; Govindarajalu, S.; Dzietko, M.; Pesditschek, S.; Mai, I.; Dirkanian, K.; et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc. Natl. Acad. Sci. USA 2002, 99, 15089–15094. [Google Scholar] [CrossRef] [Green Version]
- Katz, I.; Kim, J.; Gale, K.; Kondratyev, A. Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain. J. Pharm. Exp. 2007, 322, 494–500. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.S.; Kondratyev, A.; Tomita, Y.; Gale, K. Neurodevelopmental impact of antiepileptic drugs and seizures in the immature brain. Epilepsia 2007, 48 (Suppl. 5), 19–26. [Google Scholar] [CrossRef] [PubMed]
- Stefovska, V.G.; Uckermann, O.; Czuczwar, M.; Smitka, M.; Czuczwar, P.; Kis, J.; Kaindl, A.M.; Turski, L.; Turski, W.A.; Ikonomidou, C. edative and anticonvulsant drugs suppress postnatal neurogenesis. Ann. Neurol. 2008, 64, 434–445. [Google Scholar] [CrossRef] [PubMed]
- Ardinger, H.H.; Atkin, J.F.; Blackston, R.D.; Elsas, L.J.; Clarren, S.K.; Livingstone, S.; Flannery, D.B.; Pellock, J.M.; Harrod, M.J.; Lammer, E.J.; et al. Verification of the fetal valproate syndrome phenotype. Am. J. Med. Genet. Part. A 1988, 29, 171–185. [Google Scholar] [CrossRef] [PubMed]
- Jones, K.L.; Lacro, R.V.; Johnson, K.A.; Adams, J. Pattern of malformations in the children of women treated with carbamazepine during pregnancy. N. Engl. J. Med. 1989, 320, 1661–1666. [Google Scholar] [CrossRef] [PubMed]
- Lindhout, D.; Omtzigt, J. Teratogenic effects of antiepileptic drugs: Implications for the management of epilepsy in women of childbearing age. Epilepsia 1994, 35, S19–S28. [Google Scholar] [CrossRef] [PubMed]
- Kacirova, I.; Grundmann, M.; Brozmanova, H. Serum levels of valproic acid during delivery in mothers and in umbilical cord—Correlation with birth length and weight. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech. Repub. 2015, 159, 569–575. [Google Scholar] [CrossRef] [PubMed]
- Jentink, J.; Loane, M.A.; Dolk, H.; Barisic, I.; Garne, E.; Morris, J.K.; de Jong-van den Berg, L.T.; EUROCAT Antiepileptic Study Working Group. Valproic acid monotherapy in pregnancy and major congenital malformations. N. Engl. J. Med. 2010, 362, 2185–2193. [Google Scholar] [CrossRef]
- Tomson, T.; Battino, D.; Bonizzoni, E.; Craig, J.; Lindhout, D.; Sabers, A.; Perucca, E.; Vajda, F.; EURAP study group. Dose-dependent risk of malformations with antiepileptic drugs: An analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011, 10, 609–617. [Google Scholar] [CrossRef]
- Nakane, Y.; Okuma, T.; Takahashi, R. Multi-institutional study on teratogenicity and fetal toxicity of antiepileptic drugs: A report of a collaborative study group in Japan. Epilepsia 1980, 21, 663–680. [Google Scholar] [CrossRef]
- Nguyen, H.T.; Sharma, V.; McIntyre, R.S. Teratogenesis associated with antibipolar agents. Adv. Ther. 2009, 26, 281–294. [Google Scholar] [CrossRef] [PubMed]
- Youngs, R.M.; Chu, M.S.; Meloni, E.G.; Naydenov, A.; Carlezon, W.A.; Konradi, C. Lithium Administration to Preadolescent Rats Causes Long-Lasting Increases in Anxiety-Like Behavior and Has Molecular Consequences. J. Neurosci. 2006, 26, 6031–6039. [Google Scholar] [CrossRef] [PubMed]
- Abu-Taweel, G.M. Effects of perinatal exposure of lithium on neuro-behaviour of developing mice offspring. Indian J. Exp. Biol. 2012, 50, 696–701. [Google Scholar] [PubMed]
- van der Lugt, N.M.; van de Maat, J.S.; van Kamp, I.L.; Knoppert-van der Klein, E.A.; Hovens, J.G.; Walther, F.J. Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies. Early Hum. Dev. 2012, 88, 375–378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Galbally, M.; Roberts, M.; Buist, A. Mood stabilizers in pregnancy: A systematic review. Aust. N. Z. J. Psychiatry 2010, 44, 967–977. [Google Scholar]
- Singh, K.P.; Jaiswal, A.K.; Singh, M.; Bhattacharya, S.K. Behavioural alterations in rats induced by single prenatal exposure of haloperidol. Indian J. Exp. Biol. 1998, 36, 1102–1107. [Google Scholar] [PubMed]
- Singh, K.P.; Singh, M. Effect of prenatal haloperidol exposure on behavioral alterations in rats. Neurotoxicol. Teratol. 2002, 24, 497–502. [Google Scholar] [CrossRef]
- Rosengarten, H.; Quartermain, D. Effect of prenatal administration of haloperidol, risperidone, quetiapine and olanzapine on spatial learning and retention in adult rats. Pharm. Biochem. Behav. 2002, 72, 575–579. [Google Scholar] [CrossRef]
- Zuo, J.; Liu, Z.; Ouyang, X.; Liu, H.; Hao, Y.; Xu, L.; Lu, X.H. Distinct neurobehavioral consequences of prenatal exposure to sulpiride (SUL) and risperidone (RIS) in rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 2008, 32, 387–397. [Google Scholar] [CrossRef]
- Peng, M.; Gao, K.; Ding, Y.; Ou, J.; Calabrese, J.R.; Wu, R.; Zhao, J. Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: A case-controlled, prospective study. Psychopharmacology 2013, 228, 577–584. [Google Scholar] [CrossRef]
- Shao, P.; Ou, J.; Peng, M.; Zhao, J.; Chen, J.; Wu, R. Effects of Clozapine and other Atypical Antipsychotics on Infants Development Who Were Exposed to as Fetus: A Post-Hoc Analysis. PLoS ONE 2015, 10, e0123373. [Google Scholar] [CrossRef] [PubMed]
- Yochum, C.L.; Dowling, P.; Reuhl, K.R.; Wagner, G.C.; Ming, X. VPA-induced apoptosis and behavioral deficits in neonatal mice. Brain Res. 2008, 1203, 126–132. [Google Scholar] [CrossRef] [PubMed]
- Bromley, R.; Weston, J.; Adab, N.; Greenhalgh, J.; Sanniti, A.; McKay, A.J.; Tudur Smith, C.; Marson, A.G. Treatment for epilepsy in pregnancy: Neurodevelopmental outcomes in the child. Cochrane Database Syst. Rev. 2014, 10, CD010236. [Google Scholar] [CrossRef] [PubMed]
- Inoyama, K.; Meador, K.J. Cognitive outcomes of prenatal antiepileptic drug exposure. Epilepsy Res. 2015, 114, 89–97. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deshmukh, U.; Adams, J.; Macklin, E.A.; Dhillon, R.; McCarthy, K.D.; Dworetzky, B.; Klein, A.; Holmes, L.B. Behavioral outcomes in children exposed prenatally to lamotrigine, valproate, or carbamazepine. Neurotoxicol. Teratol. 2016, 54, 5–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meador, K.J.; Baker, G.A.; Browning, N.; Cohen, M.J.; Bromley, R.L.; Clayton-Smith, J.; Kalayjian, L.A.; Kanner, A.; Liporace, J.D.; Pennell, P.B.; et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): A prospective observational study. Lancet Neurol. 2013, 12, 244–252. [Google Scholar] [CrossRef]
- Corrado, A.C.; Walsh, J.P. Mechanisms underlying the benefits of anticonvulsants over lithium in the treatment of bipolar disorder. Neuroreport 2016, 27, 131–135. [Google Scholar] [CrossRef]
- Leo, R.J.; Narendran, R. Anticonvulsant use in the treatment of bipolar disorder: A primer for primary care physicians. Prim. Care Companion J. Clin. Psychiatry 1999, 1, 74–84. [Google Scholar] [CrossRef]
- Samrén, E.B.; Van duijn, C.M.; Christiaens, G.C.; Hofman, A.; Lindhout, D. Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann. Neurol. 1999, 46, 739–746. [Google Scholar] [CrossRef]
- Vajda, F.J.; O’Brien, T.J.; Graham, J.; Lander, C.M.; Eadie, M.J. Is carbamazepine a human teratogen? J. Clin. Neurosci. 2016, 23, 34–37. [Google Scholar] [CrossRef]
- Gentile, S. Lithium in pregnancy: The need to treat, the duty to ensure safety. Expert Opin. Drug Saf. 2012, 11, 425–437. [Google Scholar] [CrossRef] [PubMed]
- Costoloni, G.; Pierantozzi, E.; Goracci, A.; Bolognesi, S.; Fagiolini, A. Mood stabilisers and pregnancy outcomes—A review. Psychiatr. Pol. 2014, 48, 865–887. [Google Scholar] [CrossRef] [PubMed]
- U.S. Food and Drug Administration. Available online: http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm (accessed on 15 July 2019).
- Morgan, M.A.; Cragan, J.D.; Goldenberg, R.L.; Rasmussen, S.A.; Schulkin, J. Obstetrician–gynaecologist knowledge of and access to information about the risks of medication use during pregnancy. J. Matern. Fetal Neonatal Med. 2010, 23, 1143–1150. [Google Scholar] [CrossRef] [PubMed]
- Peters, S.L.; Lind, J.N.; Humphrey, J.R.; Friedman, J.M.; Honein, M.A.; Tassinari, M.S.; Moore, C.A.; Mathis, L.L.; Broussard, C.S. Safe lists for medications in pregnancy: Inadequate evidence base and inconsistent guidance from Web-based information, 2011. Pharm. Drug Saf. 2013, 22, 324–328. [Google Scholar] [CrossRef] [PubMed]
- Denton, L.K.; Creeley, C.E.; Stavola, B.; Hall, K.; Foltz, B.D. An analysis of online pregnancy message boards: Mother-to-mother advice on medication use. Women Birth 2018, 12, 3. [Google Scholar] [CrossRef]
- Mother to Baby: Medications and More During Pregnancy and Breastfeeding. Available online: https://mothertobaby.org/ (accessed on 15 July 2019).
MATERNAL DISORDER | PREGNANCY RISKS AND OUTCOMES |
---|---|
DEPRESSION DISORDERS
| |
BIPOLAR DISORDERS
| |
ANXIETY DISORDERS
| |
OBSESSIVE COMPULSIVE DISORDER |
|
SLEEP DISORDERS
|
|
Maternal Disorder | Prevalence | Age of Onset | Pregnancy Prevalence | Pregnancy Risks and Outcomes |
---|---|---|---|---|
Depression
| ~15 million (6.7% of population) | 32.5 years | 4–25% [66,67,68]
| |
Bipolar Disorders
| 3–7% [7] | 25 years | 25–30% of pregnant women experience episodes [22,42] |
|
Anxiety Disorders
| 2.7% Most prevalent disorders in U.S. [7] |
|
| |
OCD | 2.07% [57] | 19.5 [34] | 1.08% [57] |
|
Sleep Disorders
| 24%–48% [67] | Any age beginning in childhood [73] | 66%–94% [74] |
|
DRUG CLASS and NAME | TRADE NAME | CURRENT DRUG LABEL INFORMATION b |
---|---|---|
ANTIDEPRESSANTS | ||
Tri- and *Tetra-cyclics (TCAs) | ||
Amitriptyline | Elavil | Few teratogenic effects are reported, except at doses of amitriptyline which far exceed the MRHD. Results of animal research on desipramime, nortriptyline, and imipramine are described as “inconclusive.” At doses >MRHD, increased pup mortality and low body weight were reported for amoxapine and doxepin. Trimipramine exposure at 20X MRHD caused an increased risk of major abnormalities. There are no adequate and well-controlled studies in pregnant women. Adverse events in humans (central nervous systemeffects, limb deformities, developmental delays) have been reported for amitriptyline. Neonatal withdrawal and anticholinergic symptoms have been observed. The kinetics of this drug change during pregnancy, serum levels should be monitored and the dose should be adjusted if needed. |
Amoxapine | Asendin | |
Desipramine | Norpramin | |
Doxepin | Silenor | |
Nortriptyline | Aventyl, Pamelor | |
Protriptyline | Vivactil | |
Trimipramine | Surmontil | |
*Mirtazapine | Remeron | |
*Maprotiline | Ludiomil | |
Monoamine Oxidase Inhibitors (MAOIs) | ||
Phenelzine | Nardil | Phenelzine may increase fetal/pup mortality in rats. There is little information on the effects of exposure to tranylcypromine or isocarboxazid in animals. Exposure to selegiline at many times the MRHD increased the risk for major malformations (delayed ossification) and decreased fetal weight. There are no adequate and well controlled studies in pregnant women. |
Tranylcypromine | Parnate | |
Isocarboxazid | Marplan | |
Selegiline | Eldepryl, Zeladar | |
Serotonin Reuptake Inhibitors (SRIs) and *Serotonin-norepinephrine reuptake inhibitors (SNRIs) | ||
General FDA warning: A study of women with history of major depression who were euthymic at the beginning of pregnancy showed women who discontinued AD medication during pregnancy were more likely to experience a relapse than women who continued medication use. Neonates exposed late in the 3rd trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Reported clinical findings include: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo-/hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features may be a direct toxic effect or a withdrawal syndrome. In some cases, the clinical outcome is consistent with serotonin syndrome. | ||
Citalopram | Celexa | Animal studies did not suggest teratogenic effects for sertraline or escitalopram, and only at toxic doses for citalopram. At doses >MRHD, increased risk of skeletal abnormalities and decreased fetal growth/survival. There are no adequate and well-controlled studies in pregnant women. First trimester fluoxetine use is associated with increased risk of cardiovascular malformations; paroxetine is linked to cardiac malformations (ventricular septal and valve defects). Consideration should be given to either discontinuing paroxetine use or switching to another antidepressant. |
Escitalopram | Lexapro | |
Fluoxetine | Prozac, Sarafem | |
Paroxetine | Paxil | |
Sertraline | Zoloft | |
*Venlafaxine | Effexor | |
Atypical Antidepressants | ||
Bupropion | Wellbutrin | Animal studies show no clear evidence of teratogenic effects, but there is evidence of a higher pup mortality rate, and lower birth weights, at >MRHD. There are no adequate and well-controlled studies in pregnant women. |
Mirtazapine | Remeron | |
Nefazodone | Serzone | |
Trazodone | Deseryl, Oleptro | |
Vortioxetine | Trintellix | |
BENZODIAZEPINES | ||
General FDA warning: First trimester exposure linked to an increased risk of congenital malformations has been suggested in several studies. Non-teratogenic risks include reports of neonatal flaccidity, respiratory and feeding difficulties, hypothermia, and neonatal withdrawal symptoms during the postnatal period. Use of these drugs is rarely a matter of urgency, so first trimester exposure should almost always be avoided. | ||
Alprazolam | Xanax | Animal studies suggest risk for teratogenic effects; malformations (cleft palate), have been observed: temazepam has caused exencephaly and fusion or asymmetry of ribs, and is contraindicated in women who are or may become pregnant. Patients should be instructed to discontinue this drug prior to becoming pregnant. |
Clonazepam | Klonopin | |
Diazepam | Valium | |
Lorazepam | Ativan | |
Oxazepam | Serax | |
Temazepam | Restoril | |
BETA-BLOCKERS | ||
Propranolol | Inderal | In animal studies, use of propranolol at dosages at >MRHD caused embryotoxicity and neonatal toxicity. There are no adequate and well-controlled studies in pregnant women. Intrauterine growth retardation, small placentas, and congenital abnormalities have been reported in neonates whose mothers received propranolol during pregnancy. Atenolol use, especially in the 2nd trimester, is associated with infants small for gestational age. Studies with first trimester use are limited. |
Atenolol | Tenormin |
ANTIPSYCHOTICS—Typical* and Atypical/Second Generation | ||
---|---|---|
General FDA warning: Third trimester exposure increases risk for neonatal extrapyramidal and/or withdrawal symptoms (EPS), including reports of agitation, hyper-/hypotonia, tremor, somnolence, respiratory distress and feeding problems. Severity varies from self-limited symptoms to intensive care unit support and prolonged hospitalization. | ||
*Haloperidol | Haldol | No teratogenic effects or fetal toxicity have been observed in animal studies involving exposure to clozapine or lurasidone. At doses >MRHD: ziprasidone caused cardiovascular malformations, quetiapine—lower fetal weights and delays in skeletal ossification; aripripazole–increased fetal/pup death, lower birth weight, and skeletal abnormalities. At >MRHD asenapine—lower pup weights and pup mortality, ziprasidone—developmental delays and neurobehavioral impairment. There are no adequate and well-controlled studies in pregnant women. Olanzapine has been associated with adverse pregnancy outcomes, including neonatal death due to cardiovascular defect, and abortion (3 therapeutic, 1 spontaneous). |
Aripripazole | Abilify | |
Asenapine | Saphris | |
Clozapine | Clozaril | |
Lurasidone | Latuda | |
Olanzapine | Zyprexa | |
Rispiridone | Risperdal | |
Quetiapine | Seroquel | |
Ziprasidone | Geodon | |
MOOD STABILIZERS/ ANTIEPILEPTIC DRUGS | ||
Lithium | Eskalith, Lithobid | There are no adequate and well-controlled studies in pregnant women. Lithium may cause Ebstein’s anomaly. Carbamazepine is associated with risk to the fetus, including congenital malformations (spinal bifida), and developmental delays. Valproate may produce congenital malformations (e.g., neural tube defects) at a rate higher than other antiepileptic drugs; other complications include neonatal hepatic failure and hypoglycemia; long-term effects include low IQ and a greater risk for autism spectrum disorderin children. Valproate should not be used to treat women with epilepsy who are pregnant or who plan to become pregnant. If a woman becomes pregnant while taking trimethadione, termination of the pregnancy should be considered. Trimethadione and phenytoin may be associated with a neonatal coagulation defect that may cause bleeding during the early neonatal period (prophylactic Vitamin K may be indicated). Prenatal exposure to phenytoin is associated with a greater risk of neuroblastoma. Risk of use of this class of medications appears particularly high in the 1st trimester. However, abrupt discontinuation of antiepileptic drugs in mothers who use them to prevent major seizures should be avoided as this also creates risk. |
Phenytoin | Dilantin | |
Phenobarbital | Luminal | |
Valproate | Depakote | |
Trimethadione | Tridione | |
Levitiracetam | Keppra | |
Carbemazepine | Tegretol | |
Lamotrigine | Lamictal | |
SEDATIVES AND HYPNOTICS | ||
Eszopiclone | Lunesta | In animal studies, there is no evidence of teratogenic effects. Offspring of rats exposed to doses higher than the MRHD showed some evidence of delayed ossification, and decreased pup weights/survival. Fewer adverse effects have been found in studies using rabbits. There are no adequate and well-controlled studies in pregnant women. Cases of severe neonatal respiratory depression have been reported when Zolpidem was used at the end of pregnancy, especially when taken with other CNS-depressants |
Zaleplon | Sonata | |
Zolpidem | Ambien |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Creeley, C.E.; Denton, L.K. Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes. Brain Sci. 2019, 9, 235. https://doi.org/10.3390/brainsci9090235
Creeley CE, Denton LK. Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes. Brain Sciences. 2019; 9(9):235. https://doi.org/10.3390/brainsci9090235
Chicago/Turabian StyleCreeley, Catherine E., and Lisa K. Denton. 2019. "Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes" Brain Sciences 9, no. 9: 235. https://doi.org/10.3390/brainsci9090235