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Effects of Antidepressants During Pregnancy and Lactation

  • Published:
Annals of Clinical Psychiatry

Abstract

Depression is one of the most common psychiatric disorders. A variety of different chemical structures have been found to have antidepressant activity. The number is constantly growing; however, as yet, no one group has been found to have a clear therapeutic advantage over the others. The major indication for antidepressant drugs is depression, but a number of side effects have been established by clinical experience and controlled trials. It is clear that, to some extent, any drug or chemical substance administered to the mother is able to cross the placenta unless it is destroyed or altered during metabolism. Placental transport of maternal substrates to the fetus and of substances from the fetus to the mother is established at about the fifth week of fetal life. Traditionally, teratogenic effects of antidepressants or other drugs have been noted as anatomic malformation. It is clear that these are dose- and time-related and that the fetus is at great risk during the first 3 months of gestation. However, it is possible for antidepressants to exert their effects on the fetus at other times during pregnancy as well as to infants during lactation. Administration of antidepressants to pregnant women presents a unique problem for the physician. Not only must maternal pharmacologic mechanisms be taken into consideration when prescribing an antidepressant drug, but the fetus must also be regarded as a potential recipient of the drug. Certain results are evident with regard to drugs administered during lactation. It is essential that physicians need to be aware of the results of animal studies in this area and of the potential risk of maternal drug ingestion to the suckling infant.

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REFERENCES

  1. Cohen LS, Heller VL, Rosenbaum JF: Treatment guidelines for psychotropic drug use in pregnancy. Psychosomatics 1989; 30:25–33

    Google Scholar 

  2. Miller LJ: Psychiatric medication during pregnancy: Understanding and minimizing the risks. Psychiatr Annals 1994; 24:69–75

    Google Scholar 

  3. Robinson HE, Stewart DE, Flak E: The rational use of psychotropic drugs in pregnancy and postpartum. Can J Psychiatry 1986; 31:183–190

    Google Scholar 

  4. Stowe ZN, Nemeroff CB: Psychopharmacology during pregnancy and lactation. In: Schatzberg AF, Nemeroff CB. Textbook of Psychopharmacology. Washington DC: American Psychiatric Press; 1995: 823–837

    Google Scholar 

  5. Wisner KL, Perel JM: Psychopharmacologic agents and electroconvulsive consultation in childbirth settings. In: Cohen RL. Parent-and Child-Oriented Approaches. New York: Plenum Medical; 1988

    Google Scholar 

  6. Wilson JT, Brown RD, Hinson JL, Daily JW: Pharmacokinetic pitfalls in the estimation of the breast milk plasma ration for drugs. Ann Rev Pharmacol Toxicol 1985; 25:667–689

    Google Scholar 

  7. Kacew S: Adverse effects of drugs and chemicals in breast milk on the nursing infant. J Clin Pharmacol 1993; 33:213–221.

    Google Scholar 

  8. Warner A: Drug use in the neonate: Inter-relationships of pharmacokinetics, toxicity and biochemical maturity. Clin Chem 1986; 32:721–722

    Google Scholar 

  9. Atkinson HC, Begg EJ, Darlow BA: Drugs in human milk: Clinical pharmacokinetic considerations. Clin Pharmacokinetic 1988; 14:217–240

    Google Scholar 

  10. Welch R, Findlay J: Excretion of drugs in human breast milk. Drug Metab Rev 1981; 12:261–277

    Google Scholar 

  11. Shepard TH: Catalog of Teratogenic Agents, 6th Ed. Baltimore: Johns Hopkins University Press; 1989: 345–346

    Google Scholar 

  12. McBride WG: Limb deformities associated with iminodibenzyl hydrochloride. Med J Aust 1972; 1:492

    Google Scholar 

  13. Heeinonen OP, Slone D, Shapiro S: Birth Defects and Drugs in Pregnancy. Massachusetts: Publishing Sciences Group; 1977: 336–337

    Google Scholar 

  14. Kuenssberg EV, Knox JDE: Imipramine in pregnancy. Br Med J 1972; 2:29

    Google Scholar 

  15. Barson AJ: Malformed infant. Br Med J 1972; 2:45

    Google Scholar 

  16. Idanpaan-Heikkila J, Saxen L: Possible teratogenicity of imipramine/chloropyramine. Lancet 1973; 2:282–283

    Google Scholar 

  17. Crombie DL, Pinsent R, Fleming D: Imipramine in pregnancy. Br Med J 1972; 1:745

    Google Scholar 

  18. Sim M: Imipramine and pregancy. Br Med J 1972; 2:45

    Google Scholar 

  19. Scanlon FJ: Use of antidepressant drugs during the first trimester. Med J Aust 1989; 2:1077

    Google Scholar 

  20. Rachelefsky GS, Flynt JW, Eggin AJ, Wilson MG: Possible teratogenicity of tricyclic antidepressants. Lancet 1972; 1:838

    Google Scholar 

  21. Banister P, Dafoe C, Smith ESO, Miller J: Possible teratogenicity of tricyclic antidepressants. Lancet 1972; 1:838–839

    Google Scholar 

  22. Jacobs D: Imipramine (Tofranil). South Afr Med J 1972; 46:1023

    Google Scholar 

  23. Australian Drug Evaluation Committee. Tricyclic antidepressant and limb reduction deformities. Med J Aust 1973; 1:766–769

    Google Scholar 

  24. Morrow AW: Imipramine and congenital abnormalities. N Z Med J 1972; 75:228–229

    Google Scholar 

  25. Wilson JG: Present status of drugs as teratogens in man. Teratology 1973; 7:3–15

    Google Scholar 

  26. Rosa F: Medicaid antidepressants pregnancy exposure outcomes. Reprod Toxicol 1994; 8:444–445

    Google Scholar 

  27. Hill RM: Will this drug harm the unborn infant? South Med J 1977; 67:1476–1480

    Google Scholar 

  28. Eggermont E: Withdrawal symptoms in neonate associated with maternal imipramine therapy. Lancet 1973; 2:680

    Google Scholar 

  29. Shrand H: Agoraphobia and imipramine withdrawal? Pediatrics 1982; 70:825

    Google Scholar 

  30. American Academy of Pediatrics Committee on Drugs: The transfer of drugs and other chemicals into human milk. Pediatrics 1994; 93:137–150

    Google Scholar 

  31. Sovner R, Orsulak PJ: Excretion of imipramine and desipramine in human breast milk. Am J Psychiatry 1979; 136:451–452

    Google Scholar 

  32. Erickson SH, Smith GH, Heidrich F: Tricyclics and breast feeding. Am J Psychiatry 1979; 136:1483

    Google Scholar 

  33. Physicians' Desk Reference, 52nd Ed. New Jersey: Medical Economics Company Inc.; 1998

  34. Webster PA: Withdrawal symptoms in neonates associated with maternal antidepressant therapy. Lancet 1973; 2:318–319

    Google Scholar 

  35. Stancer HC, Reed KL: Desipramine and 2-hydroxydesipramine in human breast milk and the nursing infant's serum. Am J Psychiatry 1986; 143:1597–1600

    Google Scholar 

  36. Elia J, Katz IR, Simpson GM: Teratogenicity of psychotherapeutic medication. Psychopharmacol Bull 1987; 23:531–586

    Google Scholar 

  37. Freeman R. Limb deformities: Possible association with drugs. Med J Aust 1972; 1:606

    Google Scholar 

  38. Golden SM, Perman KI: Bilateral clinical anopthalmia: Drugs as potential factors. South Med J 1980; 73:1404–1407

    Google Scholar 

  39. Wertelecki W, Purvis Smith SG, Blackburn WR: Amitriptyline/perphenazine maternal overdose and birth defects (Abstract). Teratology 1980; 21:74A

    Google Scholar 

  40. Rafla NM, Meehan FP: Thanatophoric dwarfism—-drugs and antenatal diagnosis: A case report. Eur J Obstet Gynecol Reprod Biol 1990: 38:161–165

    Google Scholar 

  41. Bader TF, Newman K: Amitriptyline in human breast milk and the nursing infant's serum. Am J Psychiatry 1980; 137:855–856

    Google Scholar 

  42. Wilson JT, Brown D, Cherek DR, Dailey JW, Hilman B, Jobe PC, Manno BR, Manno JE, Redetzki HM, Strewart JJ: Drug excretion in human breast milk. Principles, pharmacokinetics and projected consequences. Clin Pharmacokinet 1980; 5:1–66

    Google Scholar 

  43. Brixen-Rasmussen L, Halgrener J, Jorgensen A: Amitriptyline and nortriptyline excretion in human breast milk. Psychopharmacology (Berlin) 1982; 76:94–95

    Google Scholar 

  44. Bourke GM: Antidepressant teratogenicity. Lancet 1974; 1:98

    Google Scholar 

  45. Shearer WT, Schreiner RL, Marshall RE: Urinary retention in a neonate secondary to maternal ingestion of nortriptyline. J Pediatr 1972; 81:570–572

    Google Scholar 

  46. Matheson I, Skjaeraasen J: Milk concentrations of flupenthixol, nortriptyline and zuclopenthixol and between-breast differences in two patients. Eur J Clin Pharmacol 1988; 35;217–220

    Google Scholar 

  47. Wisner KL, Perel JM: Serum nortriptyline levels in nursing mothers and their infants. Am J Psychiatry 1991; 148:1234–1236

    Google Scholar 

  48. Owaki Y, Momiyama H, Onodera N: Effects of doxepin hydrochloride administered to pregnant rats upon the fetuses and their postnatal development. Oyo Yakuri 1971; 5:913–924. As cited in: Shepard TH. Catalog of Teratogenic Agents, 6th Ed. Baltimore: Johns Hopkins University Press; 1989:243

    Google Scholar 

  49. Owaki Y, Momiyama H, Onodera N: Effects of doxepin hydrochloride administered to pregnant rabbits upon the fetuses. Oyo Yakuri 1971; 5:905–912. As cited in: Shepard TH. Catalog of Teratogenic Agents, 6th Ed. Baltimore: Johns Hopkins University Press; 1989: 243

    Google Scholar 

  50. Falterman CG, Richardson CJ: Small left colon syndrome associated with maternal ingestion of psychotropic drugs. J Pediatr 1980; 97:308–310

    Google Scholar 

  51. Matheson I, Pande H, Alertsen AR: Respiratory depression caused by N-desmethyldoxepin in human milk. Lancet 1985; 2:1124

    Google Scholar 

  52. Kemp J, Ilett KF, Booth J, Hackett LP: Excretion of doxepin and N-desmethyldoxepin in human milk. Br J Clin Pharmacol 1985; 20:497–499

    Google Scholar 

  53. Watenabe N, Nakai T, Iwanami K, Fujii T: Toxicological studies of clomipramine hydrochloride. Kiso to Rinsho 1970; 4:2105–2124. As cited in: Shepard TH. Catalog of Teratogenic Agents, 6th Ed. Baltimore: Johns Hopkins University Press, 1989: 159–160

    Google Scholar 

  54. Ben Muza A, Smith CS: Neonatal effects of maternal clomipramine treatment. Arch Dis Child 1979; 54:405

    Google Scholar 

  55. Schimmell MS, Katz EZ, Shaag Y, Pastuszak A, Koren G: Toxic neonatal effects following maternal clomipramine therapy. J Toxicol Clin Toxicol 1991; 29:479–484

    Google Scholar 

  56. Ostergaard GZ, Pedersen SE: Neonatal effects of maternal clomipramine treatment. Pediatrics 1982; 69:233–234

    Google Scholar 

  57. Cowe L, Lloyd DJ, Dawling S: Neonatal convulsions caused by withdrawal from maternal clomipramine. Br Med J 1982; 284:1837–1838

    Google Scholar 

  58. USP DI® Drug Information for the Health Care Professional. Vol. 1, 18th Ed. Maryland: The United States Pharmacopeial Convention, Inc.; 1998

  59. Donald FK, Lewis PR: Current Psychotherapic Drugs. New York: Brunner/Mazel Publishers; 1996

    Google Scholar 

  60. Sir CD: Therapeutic Drugs, Vol. 1. New York: Churchill Livingstone Inc.; 1991

    Google Scholar 

  61. Cooper GL: The safety of fluoxetine—-an update. Br J Psychiatry 1988;153(suppl 3):77–86

    Google Scholar 

  62. Pohland RC, Bryd TK, Hamilton M, Koons JR: Placental transfer and fetal distribution of fluoxetine in the rat. Toxicol Appl Pharmacol 1989; 98:198–205

    Google Scholar 

  63. Christina DC, Kathleen AJ, Lyn MD, Robert JF, Kenneth LJ: Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996; 335:1010–1015

    Google Scholar 

  64. Spencer DJ: Fluoxetine hydrochloride (Prozac) toxicity in a neonate. Pediatrics 1993; 92:721–722

    Google Scholar 

  65. Fuller RW, Snoddy HD, Perry KW, Bymaster FP, Wong DT: Importance of duration of drug action in the antagonism of p-choroamphetamine depletion of brain serotonin—-comparison of fluoxetine and chlorimipramine. Biochem Pharmacol 1978; 27:193–198

    Google Scholar 

  66. David JG: Effects of third trimester fluoxetine exposure on the newborn. J Clin Psychopharmacol 1995; 15:417–420

    Google Scholar 

  67. Pastuszak A, Schick-Boschetto B, Zuber C, Feldkamp M, Pinelli M, Sihn S, Donnenfeld A, McCormack M, Leen-Mitchell M, Woodland C, Gardner A, Hom M, Koren G: Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac). JAMA 1993; 269:2246–2248

    Google Scholar 

  68. AHFS Drug Information. Maryland: Society of Health System Pharmacists, Inc.; 1999

  69. Isenberg KE: Excretion of fluoxetine in human breast milk. J Clin Psychiatry 1990; 51:169

    Google Scholar 

  70. Katherine LW, James MP, Robert LF: Antidepressant treatment during breast-feeding. Am J Psychiatry 1996; 9:1132–1136

    Google Scholar 

  71. USP DI® Advice for the Patient. Drug Information in Lay Language, Vol. II, 18th Ed. Maryland: The United States Pharmocopeial Convention, Inc.; 1998

  72. Stowe ZN, Owens MJ, Landry JC, Kilts CD, Ely T, Llewellyn A, Nemeroff CB: Sertraline and desmethylsertraline in human breast milk and nursing infants. Am J Psychiatry 1997; 154:1255–1260

    Google Scholar 

  73. AHFS Drug Information. Maryland: Society of Health System Pharmacists, Inc.; 1998

  74. Mosby's GenRx—-The Complete Reference for Generic and Brand Drugs, 9th Ed. Missouri: Mosby Year Book Inc.; 1999

  75. Medical Sciences Bulletin. Celexa for the treatment of depression. The Internet-Enhanced Journal of Pharmacology and Therapeutic 1998(August); 251

  76. Mosby's GenRx—-The Complete Reference for Generic and Brand Drugs, 8th Ed. Missouri: Mosby Year Book Inc.; 1998

  77. Esaki K, Tanioka Y, Tsukada M, Izumiyama K: Teratogenicity of maprotiline tested by oral administration to mice and rats (Japanese). CIEA Preclinical Report 1976:2:69–77. As cited in: Shepard TH: Catalog of Teratogenic Agents, 6th Ed. Baltimore: Johns Hopkins University Press, 1989: 384

    Google Scholar 

  78. PDR Generics, 4th Ed. New Jersey: Mediacal Economics Company, Inc.; 1998

  79. Verbeeck RK, Ross SG, McKenna EA: Excretion of trazodone in breast milk. Br J Clin Pharmacol 1986; 22:367–370

    Google Scholar 

  80. Weintraub M, Evan P: Buproprion: A chemically and pharmacologically unique antidepressant. Hosp Form 1989; 24:254–259

    Google Scholar 

  81. Physician's Desk Reference, 53rd Ed. New Jersey: Medical Economics Company; 1999

  82. Briggs GG, Samson JH, Ambrose PJ, Schroeder DH: Excretion of buproprion in breast milk. Ann Pharmacother 1993; 27:431–433

    Google Scholar 

  83. Gelenberg AJ: Amoxapine, a new antidepressant, appears in human milk. J Nerv Ment Dis 1979; 167:635–636

    Google Scholar 

  84. Da-Silva VA, Moraes-Santos AR, Carvalho MS, Teixeira NA: Prenatal and postnatal depression among low income Brazilian women. Braz J Med Biol Res 1998; 31(6):799–804

    Google Scholar 

  85. Murata A, Nadaoka T, Morioka Y, Oiji A, Saito H: Prevalence and background factors of maternity blues. Gynecol Obstet Invest 1998; 46(2):99–104

    Google Scholar 

  86. Nonacs R, Cohen LS: Postpartum mood disorders: Diagnosis and treatment guidelines. J Clin Psychiatry 1998; 59(Suppl 2):34–40

    Google Scholar 

  87. Pariser SF, Nasrallah HA, Gardner DK: Postpartum mood disorders: Clinical perspectives. J Wom Health 1997; 6(4): 421–434

    Google Scholar 

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  1. Department of Epidemiology and International Health, School of Public Health, The University of Alabama at Birmingham, Birmingham, Alabama, 35205

    Mohammad Masud Iqbal

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Iqbal, M.M. Effects of Antidepressants During Pregnancy and Lactation. Ann Clin Psychiatry 11, 237–256 (1999). https://doi.org/10.1023/A:1022317630703

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