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J Psychiatry Neurosci. 1998 September; 23(4): 223–228.
PMCID: PMC1188938

Valproic acid use in psychiatry: issues in treating women of reproductive age.

Abstract

Valproic acid, a well known anticonvulsant, is being used by psychiatrists increasingly to manage bipolar and other affective disorders. Because of the demographics of the population affected by such psychiatric conditions, more women of childbearing age are likely to be exposed to this teratogenic drug. Neural tube defects (NTD) are the most common of the major anomalies associated with in utero valproic acid exposure, and are estimated to occur in 1% to 2% of exposed fetuses. Other teratogenic effects include facial dysmorphism, congenital cardiac defects, limb reduction defects and other skeletal anomalies. Prenatal diagnosis, in particular maternal serum alpha-fetoprotein screening and targeted ultrasonography, should be offered to all pregnant women exposed to valproic acid and couples need to be aware of the prenatal diagnostic options available to them. Periconceptual prophylaxis with high doses of folic acid is recommended for all women on valproic acid and counselling should also emphasize planning pregnancy to optimize folic acid supplementation. Psychiatrists should be aware of the teratogenic potential of valproic acid and know how to counsel their patients of reproductive age.

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Selected References

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  • Gerner RH, Stanton A. Algorithm for patient management of acute manic states: lithium, valproate, or carbamazepine? J Clin Psychopharmacol. 1992 Feb;12(1 Suppl):57S–63S. [PubMed]
  • Gelenberg AJ, Kane JM, Keller MB, Lavori P, Rosenbaum JF, Cole K, Lavelle J. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med. 1989 Nov 30;321(22):1489–1493. [PubMed]
  • Keller MB, Lavori PW, Kane JM, Gelenberg AJ, Rosenbaum JF, Walzer EA, Baker LA. Subsyndromal symptoms in bipolar disorder. A comparison of standard and low serum levels of lithium. Arch Gen Psychiatry. 1992 May;49(5):371–376. [PubMed]
  • Phillips NI, Fowler LJ. The effects of sodium valproate on gamma-aminobutyrate metabolism and behaviour in naive and ethanolamine-O-sulphate pretreated rats and mice. Biochem Pharmacol. 1982 Jul 1;31(13):2257–2261. [PubMed]
  • Chapman A, Keane PE, Meldrum BS, Simiand J, Vernieres JC. Mechanism of anticonvulsant action of valproate. Prog Neurobiol. 1982;19(4):315–359. [PubMed]
  • Pope HG, Jr, McElroy SL, Keck PE, Jr, Hudson JI. Valproate in the treatment of acute mania. A placebo-controlled study. Arch Gen Psychiatry. 1991 Jan;48(1):62–68. [PubMed]
  • Bowden CL, Brugger AM, Swann AC, Calabrese JR, Janicak PG, Petty F, Dilsaver SC, Davis JM, Rush AJ, Small JG, et al. Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA. 1994 Mar 23;271(12):918–924. [PubMed]
  • Calabrese JR, Delucchi GA. Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. Am J Psychiatry. 1990 Apr;147(4):431–434. [PubMed]
  • Brown NA, Kao J, Fabro S. Teratogenic potential of valproic acid. Lancet. 1980 Mar 22;1(8169):660–661. [PubMed]
  • Dalens B, Raynaud EJ, Gaulme J. Teratogenicity of valproic acid. J Pediatr. 1980 Aug;97(2):332–333. [PubMed]
  • Hiilesmaa VK, Bardy AH, Granström ML, Teramo KA. Valproic acid during pregnancy. Lancet. 1980 Apr 19;1(8173):883–883. [PubMed]
  • Robert E, Guibaud P. Maternal valproic acid and congenital neural tube defects. Lancet. 1982 Oct 23;2(8304):937–937. [PubMed]
  • Lindhout D, Schmidt D. In-utero exposure to valproate and neural tube defects. Lancet. 1986 Jun 14;1(8494):1392–1393. [PubMed]
  • Lindhout D, Omtzigt JG, Cornel MC. Spectrum of neural-tube defects in 34 infants prenatally exposed to antiepileptic drugs. Neurology. 1992 Apr;42(4 Suppl 5):111–118. [PubMed]
  • Van Allen MI, Kalousek DK, Chernoff GF, Juriloff D, Harris M, McGillivray BC, Yong SL, Langlois S, MacLeod PM, Chitayat D, et al. Evidence for multi-site closure of the neural tube in humans. Am J Med Genet. 1993 Oct 1;47(5):723–743. [PubMed]
  • Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med. 1991 Mar 7;324(10):674–677. [PubMed]
  • Ardinger HH, Atkin JF, Blackston RD, Elsas LJ, Clarren SK, Livingstone S, Flannery DB, Pellock JM, Harrod MJ, Lammer EJ, et al. Verification of the fetal valproate syndrome phenotype. Am J Med Genet. 1988 Jan;29(1):171–185. [PubMed]
  • Jäger-Roman E, Deichl A, Jakob S, Hartmann AM, Koch S, Rating D, Steldinger R, Nau H, Helge H. Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid. J Pediatr. 1986 Jun;108(6):997–1004. [PubMed]
  • Huot C, Gauthier M, Lebel M, Larbrisseau A. Congenital malformations associated with maternal use of valproic acid. Can J Neurol Sci. 1987 Aug;14(3):290–293. [PubMed]
  • Verloes A, Frikiche A, Gremillet C, Paquay T, Decortis T, Rigo J, Senterre J. Proximal phocomelia and radial ray aplasia in fetal valproic syndrome. Eur J Pediatr. 1990 Jan;149(4):266–267. [PubMed]
  • Okada T, Tomoda T, Hisakawa H, Kurashige T. Fetal valproate syndrome with reduction deformity of limb. Acta Paediatr Jpn. 1995 Feb;37(1):58–60. [PubMed]
  • Paulson RB, Sucheston ME, Hayes TG, Paulson GW. Teratogenic effects of valproate in the CD-1 mouse fetus. Arch Neurol. 1985 Oct;42(10):980–983. [PubMed]
  • Petrere JA, Anderson JA, Sakowski R, Fitzgerald JE, de la Iglesia FA. Teratogenesis of calcium valproate in rabbits. Teratology. 1986 Dec;34(3):263–269. [PubMed]
  • Sharony R, Garber A, Viskochil D, Schreck R, Platt LD, Ward R, Buehler BA, Graham JM., Jr Preaxial ray reduction defects as part of valproic acid embryofetopathy. Prenat Diagn. 1993 Oct;13(10):909–918. [PubMed]
  • Buntinx IM. Preaxial polydactyly in the fetal valproate syndrome. Eur J Pediatr. 1992 Dec;151(12):919–920. [PubMed]
  • Clayton-Smith J, Donnai D. Fetal valproate syndrome. J Med Genet. 1995 Sep;32(9):724–727. [PMC free article] [PubMed]
  • Chitayat D, Farrell K, Anderson L, Hall JG. Congenital abnormalities in two sibs exposed to valproic acid in utero. Am J Med Genet. 1988 Oct;31(2):369–373. [PubMed]
  • Christianson AL, Chesler N, Kromberg JG. Fetal valproate syndrome: clinical and neuro-developmental features in two sibling pairs. Dev Med Child Neurol. 1994 Apr;36(4):361–369. [PubMed]
  • DiLiberti JH, Farndon PA, Dennis NR, Curry CJ. The fetal valproate syndrome. Am J Med Genet. 1984 Nov;19(3):473–481. [PubMed]
  • Clay SA, McVie R, Chen H. Possible teratogenic effect of valproic acid. J Pediatr. 1981 Nov;99(5):828–828. [PubMed]
  • Thomas D, Buchanan N. Teratogenic effects of anticonvulsants. J Pediatr. 1981 Jul;99(1):163–163. [PubMed]
  • Jones KL, Lacro RV, Johnson KA, Adams J. Pattern of malformations in the children of women treated with carbamazepine during pregnancy. N Engl J Med. 1989 Jun 22;320(25):1661–1666. [PubMed]
  • Martínez-Frías ML. Clinical manifestation of prenatal exposure to valproic acid using case reports and epidemiologic information. Am J Med Genet. 1990 Oct;37(2):277–282. [PubMed]
  • Boussemart T, Bonneau D, Levard G, Berthier M, Oriot D. Omphalocele in a newborn baby exposed to sodium valproate in utero. Eur J Pediatr. 1995 Mar;154(3):220–221. [PubMed]
  • Thisted E, Ebbesen F. Malformations, withdrawal manifestations, and hypoglycaemia after exposure to valproate in utero. Arch Dis Child. 1993 Sep;69(3 Spec No):288–291. [PMC free article] [PubMed]
  • Brock DJ, Sutcliffe RG. Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet. 1972 Jul 29;2(7770):197–199. [PubMed]
  • Wladimiroff JW, Stewart PA, Reuss A, van Swaay E, Lindhout D, Sachs ES. The role of ultrasound in the early diagnosis of fetal structural defects following maternal anticonvulsant therapy. Ultrasound Med Biol. 1988;14(8):657–660. [PubMed]
  • Weinbaum PJ, Cassidy SB, Vintzileos AM, Campbell WA, Ciarleglio L, Nochimson DJ. Prenatal detection of a neural tube defect after fetal exposure to valproic acid. Obstet Gynecol. 1986 Mar;67(3 Suppl):31S–33S. [PubMed]
  • Guibaud S, Simplot A, Boisson C, Pison H. Dépistage prénatal de 4 cas de spina bifida chez de mères traitées par le valproate. J Genet Hum. 1987 Aug;35(4):231–235. [PubMed]
  • Brock DJ, Barron L, van Heyningen V. Prenatal diagnosis of neural-tube defects with a monoclonal antibody specific for acetylcholinesterase. Lancet. 1985 Jan 5;1(8419):5–8. [PubMed]
  • Hansen DK, Grafton TF, Dial SL, Gehring TA, Siitonen PH. Effect of supplemental folic acid on valproic acid-induced embryotoxicity and tissue zinc levels in vivo. Teratology. 1995 Nov;52(5):277–285. [PubMed]
  • Rice J, Reich T, Andreasen NC, Endicott J, Van Eerdewegh M, Fishman R, Hirschfeld RM, Klerman GL. The familial transmission of bipolar illness. Arch Gen Psychiatry. 1987 May;44(5):441–447. [PubMed]
  • Packer S. Family planning for women with bipolar disorder. Hosp Community Psychiatry. 1992 May;43(5):479–482. [PubMed]
  • Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med. 1991 Mar 7;324(10):674–677. [PubMed]
  • Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, Donnenfeld AE, Rieder M, Santelli R, Smythe J, et al. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet. 1992 Feb 29;339(8792):530–533. [PubMed]

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