Psychiatric Disorders During Pregnancy

By Stephanie Zisook, M.D., and Vivien K. Burt, M.D., Ph.D.
| January 1, 2003

Dr. Zisook is a fellow in women's health at the Neuropsychiatric Institute and Hospital at the University of California, Los Angeles. Dr. Burt is professor of clinical psychiatry and director of the Women's Life Center at UCLA's Neuropsychiatric Institute and Hospital.

In addition to spina bifida and facial abnormalities, valproic acid and carbamazepine(Drug information on carbamazepine) are associated with vitamin K-dependent clotting factor deficiency, possibly increasing the risk of bleeding in the fetus and neonate. It is not known whether folate supplementation beyond routine prenatal supplementation decreases these risks. Carbamazepine appears to increase the risk of cardiac malformations, oral clefts and urinary tract defects. Valproic acid may cause developmental delay. Because the newer anti-epileptic drugs lamotrigine(Drug information on lamotrigine) (Lamictal), gabapentin(Drug information on gabapentin) (Neurontin) and topiramate(Drug information on topiramate) (Topamax) are second-line agents for the treatment of BD and because there are very limited data for in utero exposure to these agents, these medications cannot be recommended for use in pregnancy (Morrell, 1996).

In a small (n=37) naturalistic report by Wisner et al. (2002), verapamil(Drug information on verapamil) (Calan, Isoptin) effectively treated acute manic episodes and maintained mood stability in pregnant and nonpregnant women with BD. The authors noted that verapamil does not appear to be teratogenic but that further study is needed.

Until recently, high-potency neuroleptics were considered the safest antipsychotic medications in pregnancy (Altshuler et al., 1996). However, a study by Goldstein et al. (2000) found no evidence of increased risk in 23 cases of olanzapine(Drug information on olanzapine) (Zyprexa) exposure. This raises the question of whether olanzapine should be included as a possible treatment for pregnant women requiring an antipsychotic and/or a mood stabilizer. More data are needed.

The data on benzodiazepine use in pregnancy are mixed. Overall, the data suggest a very small (12 in 10,000) but increased risk of oral clefts associated with first trimester use (Altshuler et al., 1996; Dolovich et al., 1998). Late third-trimester use of benzodiazepines can be associated with perinatal syndromes such as hypotonia, withdrawal, poor feeding, apnea and low Apgar scores (Altshuler et al., 1996; McElhatton, 1994). Infrequent use, however, doesnot appear problematic.

When carried out with a multidisciplinary treatment team comprising a psychiatrist, anesthesiologist and obstetrician, ECT is safe in pregnancy and can rapidly treat severe psychiatric illness, including psychotic depression and uncontrollable mania (Miller, 1994). Special precautions must be taken during the procedure.

Conclusion

When treating women during pregnancy, a careful review of the most recent research is essential. A number of pharmaceutical manufacturers maintain registries of pregnancy outcomes in women using psychotropic medications. Referring to the Expert Consensus Guideline Series: Treatment of Depression in Women (Altshuler et al., 2001) and obtaining a consultation from a perinatal psychiatrist who specializes in treating women of childbearing age can be extremely helpful.

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References
1. Altshuler LL, Cohen LS, Moline ML et al. (2001), The Expert Consensus Guideline Series. Treatment of depression in women. Postgrad Med (Spec No):1-107.
2. Altshuler LL, Cohen L, Szuba MP et al. (1996), Pharmacological management of psychiatric illness during preganancy: dilemmas and guidelines. Am J Psychiatry 153(5):592-606 [see comment].
3. Briggs GG, Freeman RK, Yaffe SJ (1997), Drugs in Pregnancy and Lactation, 5th ed. Baltimore: Williams & Wilkins, pp620-625.
4. Buttolph ML, Holland AD (1990), Obsessive-compulsive disorder in pregnancy and childbirth. In: Obsessive-Compulsive Disorders: Theory and Management, Jenike MA, Baer L, Minichiello WE, eds. Chicago: Year Book Medical Publishers, pp89-95.
5. Burt VK, Hendrick VC (2001), Concise Guide to Women's Mental Heath. Washington, D.C.: American Psychiatric Publishing Inc.
6. Cohen LS, Friedman JM, Jefferson JW et al. (1994), A reevaluation of risk of in utero exposure to lithium. [Published erratum JAMA 271(19):1485.] JAMA 271(2):146-150 [see comment].
7. Dolovich LR, Addis A, Vaillancourt JM et al. (1998), Benzodiazepine use in pregnancy and major malformations or oral cleft: meta-analysis of cohort and case-control studies. BMJ 317(7162):839-843 [see comments].
8. Einarson A, Fatoye B, Sarkar M et al. (2001), Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry 158(10):1728-1730.
9. Franko DL, Blais MA, Becker AE et al. (2001), Pregnancy complications and neonatal outcomes in women with eating disorders. Am J Psychiatry 158(9):1461-1466.
10. Goldstein DJ, Corbin LA, Fung MC (2000), Olanzapine-exposed pregnancies and lactation: early experience. J Clin Psychopharmacol 20(4):399-403.
11. Gotlib IH, Whiffen VE, Mount JH et al. (1989), Prevalence rates and demographic characteristics associated with depression in pregnancy and the postpartum. J Consult Clin Psychol 57(2):269-274.
12. McElhatton PR (1994), The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol 8(6):461-475.
13. McNeil TF, Kaij L, Malmquist-Larsson A (1984), Women and nonorganic psychosis: factors associated with pregnancy's effect on mental health. Acta Psychiatr Scand 70(3):209-219.
14. Miller LJ (1994), Use of electroconvulsive therapy during pregnancy. Hosp Community Psychiatry 45(5):444-450.
15. Morell MJ (1996), The new antilepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia 37(suppl 6):S34-S44.
16. Nonacs R, Cohen LS (2002), Depression during pregnancy: diagnosis and treatment options. J Clin Psychiatry 63(suppl 7):24-30.
17. Nulman I, Rovet J, Stewart DE et al. (1997), Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 336(4):258-262.
18. O'Hara MW (1986), Social support, life events, and depression during pregnancy and the puerperium. Arch Gen Psychiatry 43(6):569-573.
19. Viguera AC, Nonacs R, Cohen LS et al. (2000), Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am J Psychiatry 157(2):179-184 [see comment].
20. Wisner KL, Peindl KS, Hanusa BH (1996), Effects of childbearing on the natural history of panic disorder with comorbid mood disorder. J Affect Disord 41(3):173-180.
21. Wisner KL, Peindl KS, Perel JM et al. (2002), Verapamil treatment for women with bipolar disorder. Biol Psychiatry 51(9):745-752.
22. Woody JN, London WL, Wilbanks GD Jr (1971), Lithium toxicity in a newborn. Pediatrics 47(1):94-96.

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Psychiatric Disorders During Pregnancy

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