Discussion
The literature is clear that women with schizophrenia are at higher risk for the obstetrical complications of preterm delivery, infants with low birth weight, and babies that are small for their gestational age. We do not currently understand what may be most important in contributing to, or predicting, a poor obstetrical outcome for these women. We suggest that treating physicians take a harm-reduction approach during pregnancy and lactation and actively encourage their patients to decrease or stop cigarette smoking, alcohol use, and drug use. We recommend assessing the stability and availability of secondary caregivers for mother and infant. Community resources that will enhance the mother’s psychiatric stability, functioning in the community, and ability to parent should be identified and put in place to ensure optimal prenatal and perinatal care.
Current information about the impact of pregnancy on the course of schizophrenia is limited and difficult to interpret; thus, treatment guidelines during this time in a woman’s life are undefined. Until more research is done, it is important that treatment recommendations reflect our current understanding of the illness course in the population with schizophrenia. Reviews by Gilbert (35) and Baldessarini (36) report that patients with schizophrenia are at greatest risk of relapse within the first 3 months after antipsychotic withdrawal and reach maximal risk within 12 months. The rate of antipsychotic withdrawal is also important: tapering medication over fewer than 2 weeks results in relapse rates that are 5 to 6 times higher than those encountered when medications are tapered over 2 months or more. These data suggest that stopping medications, especially abruptly, during pregnancy or postpartum potentially places the mother at high risk for relapse. The potential consequences of a psychotic relapse may be severe and include maternal suicide and infanticide.
These potentially serious ramifications of discontinuing medication, as well as the known potential risk of medication exposure during infant development, need to be discussed carefully with the mother. Treatment with medications should be limited to situations in which the potential risk of exposing the developing infant to medications is outweighed by the risk posed by untreated maternal illness. Thus, decisions regarding medication recommendations during pregnancy and lactation should include an evaluation of a woman’s specific symptoms, illness course, and illness severity. Physicians should clearly communicate recommendations for psychiatric management to other professionals involved in their patients’ medical care and should attempt to engage and educate members of each patient’s support system, where possible.
If possible, phenothiazines should be avoided during the first trimester, because they are associated with a statistically significant increase in congenital anomalies.
Atypical antipsychotic medications may pose unique risks to women during their reproductive years. While women taking typical antipsychotics have shown suppressed fertility rates, it appears that, when taking atypical antipsychotics, their fertility rates may approach those of the general population (37). It is therefore important that patients have access to counselling about available methods of birth control. Recent studies have found that patients treated with clozapine and olanzapine have an increased risk for significant weight gain and for developing Type 2 diabetes mellitus (38–40). Both of these medical complications carry increased risk of poor obstetrical outcomes for both mother and infant (41). Maternal diabetes during pregnancy places the developing infant at greater risk for perinatal mortality, prematurity, congenital abnormalities (neural tube defects), macrosomia (which can lead to shoulder dystocia and Caesarean section), and developing diabetes in the future.
Otherwise, because no group of medications has been identified as clearly presenting a decreased risk to developing infants, we suggest a harm-reduction approach that is best achieved by maintaining the mother on the lowest dosage possible of the medication that has proved best able to manage her psychiatric symptoms.
Owing to scant data in the literature, we are unable to recommend breast-feeding while taking any antipsychotic medication. Where mothers insist on breast-feeding, it would appear especially prudent to avoid clozapine or combinations of typical antipsychotics with dosages in the upper end of their recommended ranges, if at all possible.
It is clear that we urgently need more research in this very complex area if we are to provide more detailed information to women with schizophrenia who are pregnant or who are trying to conceive. Research using standardized diagnostic and assessment scales that attempt to track the course of schizophrenia during pregnancy and postpartum may help clarify recommendations regarding medications during this period. We also need more specific information about the safety of individual medications during pregnancy and lactation. This will require prospective studies that measure levels of medication in the mother’s plasma and breast milk and in the infant’s serum and urine. Neonatal assessment of infants exposed to medications during pregnancy and lactation will be important, as will following these children over the long term. We need to determine whether developmental difficulties can be found consistently in the group of children exposed to medication during their development but not in children with similar environmental and genetic risks who were not exposed to medications. Finally, the increased risk of diabetes and obesity that appears to accompany the use of atypical antipsychotic medication may require new guidelines for screening and treating these physical complications in pregnant women taking these medications.
References
1. Miller LJ. Sexuality, reproduction, and family planning in women with schizophrenia. Schizophr Bull 1997;23:623–35.
2. Sobel DE. Infant mortality and malformations in children of schizophrenic women. Psychiatric Quarterly 1961;35:60–4
3. Rieder RO, Rosenthal D, Wender P, Blumenthal H. The offspring of schizophrenics: fetal and neonatal death. Arch Gen Psychiatry 1975;32:200–11.
4. Walker E, Emory E. Infants at risk for psychopathology: offspring of schizophrenic patients. Child Dev 1983;54:1269–85.
5. McNeil TF. Obstetric complications in schizophrenic parents. Schizophr Res 1991;5:89–101.
6. Sacker A, Done DJ, Crow TJ. Obstetric complications in children born to parents with schizophrenia: a meta-analysis of case-control studies. Psychol Med 1996;26:279–87.
7. Bennedsen BE, Mortensen PB, Olesen AV, Henriksen, TB. Preterm birth and intra-uterine growth retardation among children of women with schizophrenia. Br J Psychiatry 1999;175:239–45.
8. McCormick MC. The contribution of low birth weight to infant morbidity and childhood mortality. N Engl J Med 1985;312:82–90.
9.Bennedsen BE. Adverse pregnancy outcome in schizophrenic women: occurrence and risk factors. Schizophr Res 1998;33:1–26.
10. Kris EB. Children of mothers maintained on pharmacotherapy during pregnancy and postpartum. Current Therapeutic Research 1965;7:785–9.
11. Stika L, Elisova K, Honzakova L, Hrochova H, Plechatova H, Strnadova J, and others. Effects of drug administration in pregnancy on children’s school behaviour. Pharm Weekbl (Sci) 1990;12:252–5.
12. Platt JE ,Friedhoff AJ, Broman SH, Bond RN, Laska E, Lin SP. Effects of prenatal exposure to neuroleptic drugs on children’s growth. Neuropsychopharmacology 1988;1:205–12.
13. Matheson I, Skjaeraasen J. Milk concentrations of flupenthixol, nortriptyline and zuclopenthixol and between-breast differences in 2 patients. Eur J Clin Pharmacol 1988;35:217–20.
14. Olesen OV, Bartels V, Poulsen JH. Perphenazine in breast milk and serum. Am J Psychiatry 1990;147:1378–79.
15. Whalley LJ, Blain PG, Prime JK. Haloperidol secreted in breast milk. BMJ 1981;282:1746–7.
16. Stewart RB, Karas B, Springer PK. Haloperidol excretion in human milk. Am J Psychiatry 1980;137:849–50.
17. Blacker KH, Weinstein BJ, Ellman GL. Mother’s milk and chlorpromazine. Am J Psychiatry 1962;119:178–9.
18. Wiles DH, Orr MW, Kolakowska T. Chlorpromazine levels in plasma and milk of nursing mothers. Br J Clin Pharmacol 1978;5:272–3.
19. Yoshida K, Smith B, Craggs M, Kumar R. Neuroleptic drugs in breast-milk: a study of pharmacokinetics and of possible adverse effects in breast-fed infants. Psychol Med 1998;28:81–91.
20. Bayley N, editor. Manual for the Bayley Scale of Infant Development. New York: Psychological Corporation; 1969.
21. Crowe TK, Deitz JC, Bennett FC. The relationship between the Bayley Scales of Infant Development and preschool gross motor and cognitive performance. Am J Occ Th 1987;41:374–8.
22. Goldstein DJ, Corbin LA, Fung MC. Olanzapine-exposed pregnancies and lactation: early experience. J Clin Psychopharmacol 2000;20:399–403.
23. McDonald AD. Maternal health and congenital defect: a prospective investigation. N Engl J Med 1958;258:767–73.
24. Kerly M. Reproductive and perinatal epidemiology. Boca Raton:CRC Press, 1999: 69.
25. Kircherner J, Berghofer A, Bolk-Werschedel D. Healthy outcome under olanzapine treatment in a pregnant woman. Pharmacopsychiatry 2000; 33:78–80.
26. Baker RW, Chengappa KN. Gastroesophageal reflux as a possible result of clozapine treatment. J Clin Psychiatry 1998;59:257.
27. Keily M. Reproductive and perinatal epidemiology. Boca Raton (FL): CRC Press; 1991. p 69.
28. Barnas C, Bergant A, Hummer M, Saria A, Fleischhacker WW. Clozapine concentrations in maternal and fetal plasma, amniotic fluid, and breast milk. Am J Psychiatry 1994;151:945.
29. HiIl RC, McIvor RJ, Wojnar-Horton RE, Hackett LP, Ilett KF. Risperidone distribution and excretion into human milk: case report and estimated infant exposure during breast-feeding. J Clin Psychopharmacol 2000;20:285–6.
30. McNeil TF, Kaij L, Malmquist-Larsson A. Women with nonorganic psychosis: pregnancy’s effect on mental health during pregnancy. Acta Psychiatr Scand 1984;70:140–8.
31. Krener P, Simmons MK, Hansen RL, Treat JN. Effect of pregnancy on psychosis: life circumstances and psychiatric symptoms. Int J Psychiatry Med 1989;19(1):65–84.
32. McNeil TF. A prospective study of postpartum psychosis in a high risk group. 2: relationships to demographic and psychiatric history characteristics. Acta Psychiatr Scand 1987;75:35–43.
33. Terp IM, Mortensen PB. Postpartum psychoses: clinical diagnoses and relative risk of admission. Br J Psychiatry 1998;172:521–6.
34. Haverkamp F, Propping P, Hilgeer T. Is there an increase of reproductive rates in schizophrenia? Arch Psychiatr Nevenkr 1982;232:439–50.
35. Gilbert PL, Harris MJ, McAdams LA, Jeste DV. Neuroleptic withdrawal in schizophrenic patients: a review of the literature. Arch Gen Psychiatry 1995;52:173–88.
36. Baldessarini RJ, Viguera AC. Neuroleptic withdrawal in schizophrenic patients. Arch Gen Psychiatry 1995;52:189–92.
37. Dickson RA, Edwards A. Clozapine and fertility. Am J Psychiatry 1997;154:582–3.
38. Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, and others. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a 5-year naturalistic study. Am J Psychiatry 2000;157:975–81.
39. Mir S, Taylor D. Atypical antipsychotics and hyperglycemia. Int J Clin Psychopharm 2001;16(2):63–73.
40. Osser DN, Najarian DM, Dufresne RL. Olanzapine increases weight and serum triglyeride levels. J Clin Psychiatry 1999;60:767–70.
41. Beck WW Jr, Roberts NS. Medical complications of pregnancy and identification of the high-risk patient. In: Beck WW Jr, editor. The national medical series for independent study. 3rd ed. Baltimore (MD): Harwal; 1993. p 56,83,88.
42. Altshuler L, Cohen L, Szuba M, Burt V, Gitlin M, Mintz J. Pharmacologic managment of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry 1996;153:592–606.
43. Cohen L, Rosenbaum JF. Psychotropic drug use during pregnancy: weighing the risks. J Clin Psychiatry 1998;59 (Suppl 2):18–28.
44. Walker A, Rosenberg M, Balaban-Gil K. Neurodevelopmental and neurobehavioral sequelae of selected substances of abuse and psychiatric medications in utero. Child Adoles Psychiatr Clin North Am 1999;8:845–67.
45. Hanson JW, Oakley GP Jr. Haloperidol and limb deformity [letter]. JAMA 1975:231(1):26.
46. Van Waes A, Van de Velde E. Safety evaluation of haloperidol in the treatment of hyperemesis gravidum. J Clin Pharmacol 1969;9:224–37.
47. Hill RM, Desmond MM, Kay JL. Extrapyramidal dysfunction in an infant of a schizophrenic mother. J Pediatr 1966;69:589–95.
48. Tamer A, McKey R, Arias D, Worley L, Fogel BJ. Phenothiazine-induced extrapyramidal dysfunction in the neonate. J Pediatr 1969;75:479–80.
49. Auerbach JG, Hans SL, Marcus J, Maeir S. Maternal psychotropic medication and neonatal behaviour. Neurotoxicol Teratol 1992;14:399–406.
50. Ben-Amitai D, Merlob P. Neonatal fever and cyanotic spells from maternal chlorpromazine. DICP, Ann Pharmacother 1991;25:1009–10.
51.Okuno S, Hamada H, Fujiki Y, Yasulka M, Watanabe H, Yamada N, and others. Transplacental exposure to antipsychotic drugs during pregnancy and megacystis in the fetus. Prenat Diagn 1999;19:980–2.
52. Ergenekon E, Atalay Y, Tunaoglu, Koc E. Transient heart block in a newborn due to maternal antipsychotic treatment during pregnancy. Eur J Paediatrics 2000;159:137–8.
53. Scokel PW, Jones WN. Infant jaundice after phenothiazine drugs for labour: an enigma. Obstet Gynecol 1962;20:124–7.
54. Falterman CG, Richardson CJ. Small left colon syndrome associated with maternal ingestion psychotropic drugs. J Pediatr 1980;97:308–10.
55. Meut C, Bavoux F, Cynober E, Lebrun F. Necrotizing enterocolitis in a newborn: maternal psychotropic drugs suspected. Can J Psychiatry 1994;39:127.
56. Robertson RT, Majka JA, Peter CP, Bokelman DL. Effects of prenatal exposure to chlorpromazine on postnatal development and behaviour of rats. Toxicol Appl Pharmacol 1980;53:541–9.
57. Clarke C, Gorman D, Vernadakes A. Effects of prenatal administration of psychotropic drugs on behavior of developing rats. Dev Psychol 1970;3:225–35.
58. Cagiano R, Barfield RJ, White NR. Subtle behavioral changes produced in rat pups by in utero exposure to haloperidol. Eur J Pharmacol 1988;157:45–50.
59. Golub M, Kornetsky C. Modification of the behavioral response to drugs in rats exposed prenatally to chlorpromazine. Psychopharmacologia 1975;43:289.
60. Tonge SR. Permanent changes in brain monoamine metabolism induced by the administration of psychotropic drugs during the pre and neonatal periods in rats. J Pharm Pharmacol 1972;24 (Suppl):149.
61. Rosengarten H, Friedhoff AJ. Enduring changes in dopamine receptor cells of pups frome drug administration to pregnant and nursing rats. Science 1979;203:1133–5.
62. Stoner SC, Sommi RW, Marken PA, Anya I, Vaughn J. Clozapine use in two full-term pregnancies. J Clin Psychiatry 1997;58:364–5.
63. Waldman MD, Safferman AZ. Pregnancy and clozapine. Am J Psychiatry 1993;150:168–9.
64. Dickson RA, Hogg L. Pregnancy of a patient treated with clozapine. Psychiatr Serv 1998;49:1081–3.
Author(s)
Manuscript received October 2001 and accepted September 2002.
Part of the information in this paper was previously presented at Grand Rounds, St Paul’s Hospital, December 8, 2000, and at the 1st World Congress in Women’s Mental Health; March 27–31, 2001; Berlin, Germany. The paper was previously presented at the 51st Annual Meeting of the Canadian Psychiatric Association; November 15–19, 2001; Montreal, Quebec.
1. Consultant Psychiatrist, Reproductive Mental Health and Community Mental Health, University of British Columbia, Vancouver, British Columbia.
2. Consultant Psychiatrist and Director, Reproductive Mental Health, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia.
3. Consultant Psychiatrist, Reproductive Mental Health, St Paul’s Hospital, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia.
4. Consultant Psychiatrist, Community Mental Health, North East Mental Health Team, University of British Columbia, Vancouver, British Columbia.
5. Research Assistant, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
Address for correspondence: Dr S Patton, British Columbia Women’s Hospital, H214 Reproductive Mental Health Program, 4500 Oak Street, Vancouver, BC V6H 3N1
e-mail: spatton@cw.bc.ca
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