Skip to main content
SpringerLink
Log in

Excretion of Psychotropic Drugs into Breast Milk

Pharmacokinetic Overview and Therapeutic Implications

  • Drug Therapy
  • Published:
CNS Drugs Aims and scope Submit manuscript

Summary

The prescription of psychotropic drugs during lactation is a clinically important but complex issue. Most of the information available on the excretion of these drugs into breast milk and the impact that this has on the breast-fed infant is based on single case reports. For many drugs, data are extremely sparse or even lacking. Although all psychotropic drugs that have been studied are excreted into breast milk, there is limited knowledge on the practical impact of the, often very low, concentrations found. On the other hand, the capacity for drug elimination is often impaired in infants compared with adults, indicating that even exposure to apparently insignificant doses through breast milk may cause adverse effects, particularly in premature neonates or after long term exposure. In addition, large methodological problems exist in the assessment of possible adverse drug reactions in neonates and infants. Nevertheless, based on current knowledge, some recommendations can be suggested.

In mothers receiving tricyclic antidepressants, it seems unwarranted to recommend that breast feeding should be discontinued. The exception to this rule is in mothers receiving doxepin. The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) fluoxetine should probably be avoided during lactation. Treatment with other SSRIs (citalopram, fluvoxamine, paroxetine or sertraline) seems to be compatible with breast feeding, although this view should be considered as preliminary due to the lack of data.

Regarding anxiolytic benzodiazepines, adverse drug reactions in infants have been described during maternal treatment with diazepam. Therefore, oxazepam seems to be preferable to diazepam in lactating women. Nevertheless, during maternal treatment with all anxiolytic benzodiazepines, infants should be observed for signs of sedation and poor suckling, and if high doses have to be used and long term administration is required, breast feeding should probably be discontinued. Hypnosedative benzodiazepines with short elimination half-lives, such as midazolam, are preferable to drugs with long half-lives, such as nitrazepam and quazepam. However, zopiclone and zolpidem are probably more appropriate than the benzodiazepines when a hypnotic drug is required.

Although animal studies have indicated that alterations in central dopaminergic systems may occur after exposure to antipsychotics through breast milk, it is not known whether these results are relevant to the situation in suckling infants. The very limited clinical data available indicate that high potency antipsychotics can be used cautiously during lactation when low doses are given. If treatment with chlorpromazine, clozapine or sulpiride is considered necessary, breast feeding should probably be discontinued.

Breast feeding should be stopped when the mother is receiving lithium. However, maternal treatment with carbamazepine or valproic acid (sodium valproate) appears to be compatible with breast feeding.

In general, if a psychotropic drug is considered necessary in a lactating mother, a drug that is minimally excreted into breast milk or that has been found in negligible amounts in the plasma of a breast-fed infant, and has not been associated with detrimental effects in infants, is preferable. Due to the considerable pharmacokinetic variability of most psychotropic drugs, therapeutic drug monitoring should be used to ensure that the mother is not treated with higher doses than are necessary. The dose received by the infant can be further reduced if breast feeding is avoided at times of peak drug concentration in the milk. As breast milk has considerable nutritional, immunological and other advantages over formula milk, the possible risks to the infant should always be carefully weighed, on an individual basis, against the benefits of continuing breast feeding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hopkins J, Marcus M, Campbell SB. Postpartum depression: acritical review. Psychol Bull 1984; 95: 498–515

    Article  PubMed  CAS  Google Scholar 

  2. Robinson GE, Stewart DE. Postpartum psychiatric disorders.Can Med Ass J 1986; 134: 31–7

    CAS  Google Scholar 

  3. Brockington IF, Cernik KF, Shofield EM, et al. Puerperal psychosis:phenomena and diagnosis. Arch Gen Psychiatry 1981;38: 829–33

    Article  PubMed  CAS  Google Scholar 

  4. Byers T, Graham S, Rzepka T, et al. Lactation and breastcancer: evidence for a negative association in premenopausalwomen. Am J Epidemiol 1985; 121: 664–74

    Article  PubMed  CAS  Google Scholar 

  5. Bertilsson L, Dahl M-L. Polymorphic drug oxidation: relevanceto the treatment of psychiatric disorders. CNS Drugs 1996;5: 200–23

    Article  CAS  Google Scholar 

  6. Tuomisto J, Männistö P. Neurotransmitter regulation of anteriorpituitary hormones. Pharmacological Rev 1985; 37: 249–332

    CAS  Google Scholar 

  7. Rubin RT. Prolactin and schizophrenia. In: Meltzer HY, editor.Psychopharmacology: the third generation of progress. NewYork: Raven Press, 1987: 803–8

    Google Scholar 

  8. Pollati FK. Sulpiride isomers and milk secretion in puerperium.Clin Exp Obstet Gynecol 1982; 9: 144–7

    Google Scholar 

  9. Aano T, Shioji T, Aki T, et al. Augmentation of puerperal lactationby oral administration of sulpiride. J Clin EndocrinolMetab 1979; 48: 478–82

    Article  Google Scholar 

  10. Jeffries J, Bezchlibnyk-Butler K, Remington G. Amennorrheaand galactorrhea associated with fluvoxamine in a loxapine-treatedpatient. J Clin Psychopharmacol 1992; 55: 336–43

    Google Scholar 

  11. Bronzo MR, Stahl SM. Galactorrhea induced by sertraline. AmJ Psychiatry 1993; 150: 1269–70

    CAS  Google Scholar 

  12. Wilson JT. Determinants and consequences of drug excretionin breast milk. Drug Metab Rev 1983: 14: 619–52

    Article  PubMed  CAS  Google Scholar 

  13. Casey C, Hambridge KM. Nutritional aspects of human lactation.In: Neville MC, Neifert MR, editors. Lactation: physiology,nutrition and breast-feeding. New York: Plenum Press,1983: 199–248

    Google Scholar 

  14. Prentice A, Prentice AM, Whitehead RG. Breast-milk fat concentrationsof rural African women: short-term variationswithin individuals. Br J Nutr 1981: 45: 483–94

    Article  PubMed  CAS  Google Scholar 

  15. Matheson I, Skjaeraasen J. Milk concentrations of flupenthixol,nortriptyline and zuclopenthixol and between-breast differencesin two patients. Eur J Clin Pharmacol 1988; 35: 217–20

    Article  PubMed  CAS  Google Scholar 

  16. Kemp J, Ilett KF, Booth J, et al. Excretion of doxepin and N-desmethyldoxepinin human milk. Br J Clin Pharmacol 1985;20: 497–9

    Article  PubMed  CAS  Google Scholar 

  17. Ilett KF, Lebedevs TH, Wojnar-Horton RE, et al. The excretionof dothiepin and its primary metabolites in breast milk. Br JClin Pharmacol 1993; 33: 635–9

    Article  Google Scholar 

  18. Dusci LJ, Good SM, Hall RE, et al. Excretion of diazepam andits metabolites in human milk during withdrawal from combinationhigh dose diazepam and oxazepam. Br J Clin Pharmacol1990; 29: 123–6

    Article  PubMed  CAS  Google Scholar 

  19. Bennett PN and the WHO working group. Drugs and humanlactation. 2nd ed. Amsterdam: Elsevier, 1996

    Google Scholar 

  20. Pecorari D. Translactal passage and pharmacotherapy of lactation.In: Kuemmerle HP, Brendel K, editors. Clinical pharmacologyin pregnancy. Stuttgart: Georg Thieme Verlag, 1984:252–9

    Google Scholar 

  21. Wilson JT, Brown DJ, Hinson JL, et al. Pharmacokinetic pitfallsin the estimation of the breast milk/plasma ratio for drugs.Ann Rev Pharmacol Toxicol 1985: 25: 667–89

    Article  CAS  Google Scholar 

  22. Anderson PO. Drugs and breast feeding. Semin Perinatol 1979;3: 271–8

    PubMed  CAS  Google Scholar 

  23. Gourley GR, Arend RA. β-glucuronidase and hyperbilirubinaemiain breast-fed and formula-fed babies. Lancet 1986; I:644–6

    Article  Google Scholar 

  24. Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokineticsin newborns and infants. Clin Pharmacokinet 1980:5: 485–527

    Article  PubMed  CAS  Google Scholar 

  25. Morselli PL. Clinical pharmacokinetics in neonates. Clin Pharmacokinet1976; 1: 81–9

    Article  PubMed  CAS  Google Scholar 

  26. Mammen GJ, editor. Clinical pharmacokinetics: drug datahandbook. 2nd ed. Auckland: Adis Press Limited, 1990

    Google Scholar 

  27. Tomson G, Lunell G–O, Sundwall A, et al. Placental passage ofoxazepam and its metabolism in mother and newborn. ClinPharmacol Ther 1979: 25: 74–81

    CAS  Google Scholar 

  28. Jacqz-Aigrain E, Daoud P, Burtin P, et al. Pharmacokinetics ofmidazolam during continuous infusion in critically ill neonates.Eur J Clin Pharmacol 1992; 42: 329–32

    Article  PubMed  CAS  Google Scholar 

  29. McDermott CA, Kowalczyk AL, Schnitzler ER, et al. Pharmacokineticsof lorazepam in critically ill neonates with seizures.J Pediatr 1992; 120: 479–83

    Article  PubMed  CAS  Google Scholar 

  30. Sjöqvist F, Bergfors PG, Borgå O, et al. Plasma clearance ofnortriptyline in a newborn infant following placental transferfrom an intoxicated mother: evidence for drug metabolism. JPediatr 1972; 80: 496–500

    Article  Google Scholar 

  31. Schimmell MS, Katz EZ, Shaag Y, et al. Toxic neonatal effectsfollowing maternal clomipramine therapy. Clin Toxicol 1991;29: 479–84

    Article  CAS  Google Scholar 

  32. Leppik IE. Metabolism of antiepileptic medication: newbornto elderly. Epilepsia 1992; 33(4 Suppl.): 32–40

    Article  Google Scholar 

  33. Kanto JH. Use of benzodiazepines during pregnancy, labourand lactation, with particular reference to pharmacokineticconsiderations. Drugs 1982: 23: 354–80

    Article  PubMed  CAS  Google Scholar 

  34. Ratanasavanh D, Beaune P, Morel F, et al. Intralobular distributionand quantitation of cytochrome P-450 enzymes in humanliver as a function of age. Hepatology 1991; 13: 1142–51

    Article  PubMed  CAS  Google Scholar 

  35. Treluyer JM, Jacqz-Aigrain E, Alvarez F, et al. Expression ofCYP2D6 in developing human liver. Eur J Biochem 1991;202: 583–8

    Article  PubMed  CAS  Google Scholar 

  36. Carrier O, Pons G, Rey E, et al. Maturation of caffeine metabolicpathways in infancy. Clin Pharmacol Ther 1988; 44:145–51

    Article  PubMed  CAS  Google Scholar 

  37. Blumer JL, Reed MD. Principles of neonatal pharmacology. In:Yaffe SJ, Aranda JV, editors. Pediatric pharmacology. Philadelphia: W.B. Saunders, 1992: 164–77

    Google Scholar 

  38. Bader TF, Newman K. Amitriptyline in human breast milk andthe nursing infant’s serum. Am J Psychiatry 1980; 137: 855–6

    PubMed  CAS  Google Scholar 

  39. Brixen-Rasmussen L, Halgrener J, Jörgensen A. Amitriptylineand nortriptyline excretion in human breast milk. Psychopharmacology1982; 76: 94–5

    Article  PubMed  CAS  Google Scholar 

  40. Breyer-Pfaff U, Nill K, Entenmann A, et al. Secretion of amitriptylineand metabolites into breast milk. Am J Psychiatry1995; 152: 812–3

    PubMed  CAS  Google Scholar 

  41. Pittard WB, O’Neil Jr W. Amitriptyline excretion in humanmilk. J Clin Psychopharmacol 1986; 6: 383–4

    Article  PubMed  Google Scholar 

  42. Gelenberg AJ. Amoxapine, a new antidepressant, appears inhuman milk. J Nerv Ment Dis 1979; 167: 635–6

    Article  PubMed  CAS  Google Scholar 

  43. Stancer HC, Reed KL. Desipramine and 2-hydroxydesipraminein human breast milk and the nursing infant’s serum. Am JPsychiatry 1986; 143: 1597–600

    CAS  Google Scholar 

  44. Rees JA, Glass RC, Sporne GA. Serum and breast milk concentrationsof dothiepin [letter]. Practioner 1976; 217: 686

    Google Scholar 

  45. Buist A, Norman TR, Dennerstein L. Plasma and breast milk concentrationsof dothiepin and northiaden in lactating women.Hum Psychopharmacol 1993; 8: 29–33

    Article  Google Scholar 

  46. Matheson I, Pande H, Alertsen AR. Respiratory depressioncaused by N-desmethyldoxepin in breast milk [letter]. Lancet1985; 2: 1124

    Article  PubMed  CAS  Google Scholar 

  47. Sovner R, Orsulak PJ. Excretion of imipramine and desipraminein human breast milk. Am J Psychiatry 1979; 136: 451–2

    PubMed  CAS  Google Scholar 

  48. Von Kobyletzki D, Herrmann B. Opipramiol in der Muttermilch.Med Welt 1970; 7: 267–9

    Google Scholar 

  49. Wisner KL, Perel JM, Foglia JR. Serum clomipramine andmetabolite levels in four nursing mother-infant pairs. J ClinPsychiatry 1995; 56: 17–20

    CAS  Google Scholar 

  50. Wisner KL, Perel JM. Serum nortriptyline levels in nursingmothers and their infants. Am J Psychiatry 1991; 148: 1234–6

    PubMed  CAS  Google Scholar 

  51. Wisner KL, Perel JM. Nortriptyline treatment of breast-feedingwomen [letter]. Am J Psychiatry 1996; 153: 295

    PubMed  CAS  Google Scholar 

  52. Balant-Gorgia EA, Balant LP. Therapeutic drug monitoring:relevance during the drug treatment of psychiatric disorders.CNS Drugs 1995; 4: 432–53

    Article  CAS  Google Scholar 

  53. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation:a preliminary report. Int J Psychiatry Med 1991; 21: 157–71

    Article  PubMed  CAS  Google Scholar 

  54. Buist A, Janson H. Effect of exposure to dothiepin and northiadenin breast milk on child development. Br J Psychiatry 1995;167: 370–3

    Article  PubMed  CAS  Google Scholar 

  55. Pons G, Rey E, Matheson I. Excretion of psychoactive drugsinto breast milk. Clin Pharmacokinet 1994; 27: 270–89

    Article  PubMed  CAS  Google Scholar 

  56. Neuropsychotherapeutics and breast-feeding — assess therisk: benefit ratio. Drug Ther Perspect 1995; 6: (2): 10–2

    Article  Google Scholar 

  57. Motorola JF. The use of psychotropic agents in pregnancy andlactation. Psychiatr Clin North Am 1989; 12: 69–87

    Google Scholar 

  58. Nurnberg HG, Prudic J. Guidelines for treatment of psychosisduring pregnancy. Hosp Comm Psychiatry 1984; 35: 67–71

    CAS  Google Scholar 

  59. American Academy of Pediatrics, Committee on Drugs. Thetransfer of drugs and other chemicals into human milk. Pediatrics1994; 93: 137–50

    Google Scholar 

  60. Spigset O, Carleborg L, Öhman R, et al. Excretion of citalopramin breast milk. Br J Clin Pharmacol 1997; 44: 295–8

    Article  PubMed  CAS  Google Scholar 

  61. Öhman I, Wikner BN, Vitols S. Citalopram and metabolite levelsin plasma and breast milk in two nursing women [abstract].Eur J Clin Pharmacol 1997; 52 Suppl.: A179

    Article  Google Scholar 

  62. Jensen PN, Olesen OV, Bertelsen A, et al. Citalopram anddesmethylcitalopram concentrations in breast milk and in serumof mother and infant. Ther Drug Monit 1997; 19: 236–9

    Article  PubMed  CAS  Google Scholar 

  63. Isenberg KE. Excretion of fluoxetine in human breast milk[letter]. J Clin Psychiatry 1990; 51: 169

    PubMed  CAS  Google Scholar 

  64. Burch KJ, Wells BG. Fluoxetine/norfluoxetine concentration inhuman milk. Pediatrics 1992; 89: 676–7

    PubMed  CAS  Google Scholar 

  65. Lester BL, Cucca J, Andreozzi L, et al. Possible association betweenfluoxetine hydrochloride and colic in an infant. J AmAcad Child Adolesc Psychiatry 1993; 32: 1253–5

    Article  CAS  Google Scholar 

  66. Taddio A, Ito S, Koren G. Excretion of fluoxetine and its metabolite,norfluoxetine, in human breast milk. J Clin Pharmacol1996; 36: 42–7

    PubMed  CAS  Google Scholar 

  67. Wright S, Dawling S, Ashford JJ. Excretion of fluvoxamine inbreast milk [letter]. Br J Clin Pharmacol 1991; 31: 209

    Article  PubMed  CAS  Google Scholar 

  68. Yoshida K, Smith B, Kumar RC. Fluvoxamine in breast milkand infant development [letter]. Br J Clin Pharmacol 1997;44: 210–1

    PubMed  CAS  Google Scholar 

  69. Spigset O, Carleborg L, Norström Å, et al. Paroxetine level inbreast milk [letter]. J Clin Psychiatry 1996; 57: 39

    PubMed  CAS  Google Scholar 

  70. Altshuler LL, Burt VK, McMullen M, et al. Breastfeeding andsertraline: a 24-hour analysis. J Clin Psychiatry 1995; 56:243–5

    PubMed  CAS  Google Scholar 

  71. Stowe ZN, Owens MJ, Landry JC, et al. Sertraline and desmethylsertralinein human breast milk and nursing infants.Am J Psychiatry 1997; 154: 1255–60

    PubMed  CAS  Google Scholar 

  72. Briggs GG, Samson JH, Ambrose PJ, et al. Excretion of bupropionin breast milk. Ann Pharmacother 1993; 27: 431–3

    PubMed  CAS  Google Scholar 

  73. Buist A, Norman T, Dennerstein L. Mianserin in breast milk. BrJ Clin Pharmacol 1993; 36: 133–4

    Article  CAS  Google Scholar 

  74. Lloyd AH. Practical consideration in the use of maprotiline(Ludiomil) in general practice. J Int Med Res 1977; 5(4Suppl.): 122–38

    PubMed  CAS  Google Scholar 

  75. Pons G, Schoerlin MP, Tarn YK, et al. Moclobemide excretionin human breast milk. Br J Clin Pharmacol 1990; 29: 27–31

    Article  PubMed  CAS  Google Scholar 

  76. Verbeeck RK, Ross SG, McKenna EA. Excretion of trazodonein breast milk. Br J Clin Pharmacol 1986; 22: 367–70

    Article  PubMed  CAS  Google Scholar 

  77. Winn S, Stowe ZN, Landry JC, et al. The effects of sertralineon nuring infants [abstract]. 1995 Annual meeting syllabusand proceedings summary. Washington, DC: American PsychiatricAssociation, 1995: 73

    Google Scholar 

  78. Oo CY, Kuhn RJ, Desai N, et al. Pharmacokinetics in lactatingwomen: prediction of alprazolam transfer into milk. Br J ClinPharmacol 1995; 40: 231–6

    Article  CAS  Google Scholar 

  79. Rey E, Giraux P, d’Athis P, et al. Pharmacokinetics of the placentaltransfer and distribution of clorazepate and its metabolitenordiazepam in the feto-placental unit and in the neonate.Eur J Clin Pharmacol 1979; 15: 181–5

    Article  PubMed  CAS  Google Scholar 

  80. Erkkola R, Kanto J. Diazepam and breast-feeding. Lancet 1972:I: 1235–6

    Article  Google Scholar 

  81. Wesson DR, Camber S, Harkey M. et al. Diazepam and desmethyldiazepamin breast milk. J Psychoactive Drugs 1985:17: 55–6

    Article  PubMed  CAS  Google Scholar 

  82. Brandt R. Passage of diazepam and desmethyldiazepam intobreast milk. Arzneimittel Forschung 1976: 26: 454–7

    PubMed  CAS  Google Scholar 

  83. Sundsbak HP, Bredesen JE. Diazepam in breast milk [in Norwegian][letter]. Tidsskr Nor Laegeforen 1980: 100: 582

    Google Scholar 

  84. Whitelaw AGL, Cummings AJ, McFadyen IR. Effect of maternallorazepam on the neonate. BMJ 1981; 282: 1106–8

    Article  PubMed  CAS  Google Scholar 

  85. Summerfield RJ, Nilsen MS. Excretion of lorazepam into breastmilk. Br J Anaesthesia 1985; 57: 1042–3

    Article  CAS  Google Scholar 

  86. Schotter A, Müller R, Gunther C, et al. Transfer of metaclazepamand its metabolites into breast milk. ArzneimittelForschung 1989; 39: 1468–70

    PubMed  CAS  Google Scholar 

  87. Wretlind M. Excretion of oxazepam in breast milk. Eur J ClinPharmacol 1987; 33: 209–10

    Article  CAS  Google Scholar 

  88. Rane A, Sundwall A, Tomson G. Oxazepam withdrawal inthe neonatal period [in Swedish]. Läkartidningen 1979; 76;4416–7

    PubMed  CAS  Google Scholar 

  89. Pacifici GM, Placidi GF. Rapid and sensitive electron-capturegas Chromatographic method for the determination ofpinazepam and its metabolites in human plasma, urine andmilk. J Chromatogr 1977; 135: 133–9

    Article  PubMed  CAS  Google Scholar 

  90. Pacifici GM, Cuoci L, Guarneri M, et al. Placental transfer ofpinazepam and its metabolite N-desmethyldiazepam in womenat term. Eur J Clin Pharmacol 1984; 27: 307–10

    Article  PubMed  CAS  Google Scholar 

  91. Brodie RR, Chasseaud LF, Taylor T. Concentrations of N-desmethylclorpropylmethylprazepamin whole blood, plasma,and milk after administration of prazepam to humans. BiopharmDrug Dispos 1981; 2: 59–68

    Article  CAS  Google Scholar 

  92. Cole AP, Hailey DM. Diazepam and active metabolite in breastmilk and their transfer to the neonate. Arch Dis Child 1975:50: 741–2

    Article  PubMed  CAS  Google Scholar 

  93. Patrick MJ, Tilstone WJ, Reavey P. Diazepam and breast-feeding.Lancet 1972; I: 542–3

    Article  Google Scholar 

  94. Jensen OH, Bredesen JE, Lindbaek E. Overgang av flunitrazepamtil morsmelk. Tidsskr Nor Laegeforen 1981; 101: 504–5

    PubMed  CAS  Google Scholar 

  95. Kanto J, Aaltonen L, Kangas L, et al. Placental transfer andbreast milk levels of flunitrazepam. Curr Ther Res 1979; 26:539–46

    CAS  Google Scholar 

  96. Hümpel M, Stoppelli I, Milia S, et al. Pharmacokinetics andbiotransformation of the new benzodiazepine, lormetazepam,in man. III. Repeated administration and transfer to neonatesvia breastmilk. Eur J Clin Pharmacol 1982; 21: 421–5

    Article  PubMed  Google Scholar 

  97. Matheson I, Lunde PKM, Bredesen JE. Midazolam and nitrazepamin the maternity ward: milk concentrations and clinicaleffects. Br J Clin Pharmacol 1990; 30: 787–93

    Article  PubMed  CAS  Google Scholar 

  98. Hubert JM, Gural RP, Symchowicz S, et al. Excretion of quazepaminto human breast milk. J Clin Pharmacol 1984; 24: 457–62

    Google Scholar 

  99. Pons G, Francoual C, Guillet PH, et al. Zolpidem excretion inbreast milk. Eur J Clin Pharmacol 1989; 37: 245–8

    Article  PubMed  CAS  Google Scholar 

  100. Gaillot J, Heusse D, Houghton GW, et al. Pharmacokinetics andmetabolism of zopiclone. Pharmacology 1983; 27(2 Suppl.):76–91

    Article  PubMed  CAS  Google Scholar 

  101. Matheson I, Sande HA, Gaillot J. The excretion of zopicloneinto breast milk. Br J Clin Pharmacol 1990; 30: 267–71

    Article  PubMed  CAS  Google Scholar 

  102. Rieder J, Wendt G. Pharmacokinetics and metabolism of thehypnotic nitrazepam. In: Garattini S, Mussini E, Randall LO,editors. The benzodiazepines. New York: Raven Press, 1973:99–127

    Google Scholar 

  103. Juul S. Barbiturate poisoning via breast milk [in Norwegian]?Tidsskr Nor Laegeforen 1969; 131: 2257–8

    CAS  Google Scholar 

  104. Kirk L, Jörgensen A. Concentrations of Cis (Z)-flupenthixol inmaternal serum, amniotic fluid, umbilical cord serum, andmilk. Psychopharmacology 1980; 72: 107–8

    Article  PubMed  CAS  Google Scholar 

  105. Whalley LJ, Blain PG, Prime JK. Haloperidol secreted in breastmilk. BMJ 1981; 282: 1746–7

    Article  PubMed  CAS  Google Scholar 

  106. Stewart RB, Karas B, Springer PK. Haloperidol excretion inhuman milk. Am J Psychiatry 1980; 137: 849–50

    PubMed  CAS  Google Scholar 

  107. Ohkubo T, Shimoyama R, Sugawara K. Measurement of haloperidolin human breast milk by high-performance liquidchromatography. J Pharm Sci 1992; 81: 947–9

    Article  PubMed  CAS  Google Scholar 

  108. Olesen OV, Bartels U, Hjelm Poulsen J. Perphenazine in breastmilk and serum. Am J Psychiatry 1990; 147: 1378–9

    PubMed  CAS  Google Scholar 

  109. Aaes-Jørgensen T, Bjørndal F, Bartels U. Zuclopenthixol levelsin serum and breast milk. Psychopharmacology 1986; 90:417–8

    Article  PubMed  Google Scholar 

  110. Blacker KH, Weinstein BJ, Ellman GL. Mothers milk and chlorpromazine.Am J Psychiatry 1962; 119: 178–9

    Google Scholar 

  111. Ohkubo T, Shimoyama R, Sugawara K. Determination ofchlorpromazine in human breast milk and serum by highperformanceliquid chromatography. J Chromatogr 1993;614: 328–32

    Article  PubMed  CAS  Google Scholar 

  112. Wiles DH, Orr MW, Kolakowska T. Chlorpromazine levels inplasma and milk of nursing mothers. Br J Clin Pharmacol1978; 5: 272–3

    Article  PubMed  CAS  Google Scholar 

  113. Matheson I, Evang A, Fredricson Overø K, et al. Presence ofchlorprothixene and its metabolites in breast milk. Eur J ClinPharmacol 1984; 27: 611–3

    Article  CAS  Google Scholar 

  114. Ohkubo T, Shimoyama R, Sugawara K. High performance liquidChromatographic determination of levomepromazine inhuman breast milk and serum using solid phase extraction.Biomed Chromatogr 1993; 7: 227–8

    Article  PubMed  CAS  Google Scholar 

  115. Barnas C, Bergant A, Hummer H, et al. Clozapine concentrationsin maternal and fetal plasma, amniotic fluid and breastmilk [letter]. Am J Psychiatry 1994; 151: 945

    PubMed  CAS  Google Scholar 

  116. Lundborg P. Abnormal ontogeny in young rabbits after chronicadministration of haloperidol to the nursing mothers. BrainRes 1972; 44: 684–7

    CAS  Google Scholar 

  117. Kellogg C, Lundborg P, Roos BE. Ontogenic changes in cerebralconcentration of homovanillic acid in response to haloperidoltreatment. Brain Res 1972; 40: 469–75

    Article  PubMed  CAS  Google Scholar 

  118. Nakanishi H, Tönjes R, Dörner G, et al. Effects of neurolepticsadministered to lactating rats on the behavioral developmentof offspring. Exp Clin Endocrinol 1986; 88: 13–24

    Article  PubMed  CAS  Google Scholar 

  119. Dobbing J, Sands J. Comparative aspects of the brain growthspurt. Early Hum Dev 1979; 3: 79–83

    Article  PubMed  CAS  Google Scholar 

  120. Kris EB, Carmichael DM. Chlorpromazine maintenance therapyduring pregnancy and confinement. Psychiatr Q 1967;31: 690–5

    Article  Google Scholar 

  121. Leonard BE. Behavioral teratology and toxicology. In: Grahame-Smith DG, Cowen PJ, editors. Preclinical psychopharmacology.Amsterdam: Excerpta Medica, 1983: 248–78

    Google Scholar 

  122. Shimizu M, Matsuda H, Sakaue N, et al. A few findings onlithium levels in mother milk [in Japanese]. Seishin ShinkeigakuZasshi 1981; 83: 399–405

    CAS  Google Scholar 

  123. Kuhnz W, Jäger-Roman E, Rating D, et al. Carbamazepine andcarbamazepine-10,11-epoxide during pregnancy and postnatalperiod in epileptic mothers and their nursed infants:pharmacokinetics and clinical effects. Pediatr Pharmacol1983; 3: 199–208

    CAS  Google Scholar 

  124. Froecher W, Eichelbaum M, Niesen M, et al. Antiepileptic therapywith carbamazepine and valproic acid during pregnancyand lactation period. In: Dam M, Gram L, Penry JK, editors.Advances in epileptology: XIIth Epilepsy International Symposium;1980 Sep 6–10; Copenhagen. New York: RavenPress, 1981: 581–8

    Google Scholar 

  125. Pynnönen S, Kant M, Sillanpää M, et al. Carbamazepine: placentaltransport, tissue concentrations in foetus and newborn,and level in milk. Acta Pharmacol Toxicol 1977; 41: 244–53

    Article  Google Scholar 

  126. Pynnönen S, Sillanpää M. Carbamazepine and mothers milk[letter]. Lancet 1975; II: 563

    Article  Google Scholar 

  127. Niebyl JR, Blake DA, Freeman JM, et al. Carbamazepine levelsin pregnancy and lactation. Obstet Gynecol 1979; 53: 139–40

    PubMed  CAS  Google Scholar 

  128. Kaneko S, Sato T, Suzuki K. The levels of anticonvulsants inbreast milk. Br J Clin Pharmacol 1979; 7: 624–7

    Article  PubMed  CAS  Google Scholar 

  129. Kaneko S, Suzuki K, Sato T, et al. The problems of antiepilepticmedication in the neonatal period: is breast feeding advisable.In: Janz D, et al, editors. Epilepsy, pregnancy and the child.New York: Raven Press, 1982: 343–8

    Google Scholar 

  130. Kok THHG, Taitz LS, Bennet MJ, et al. Drowsiness due toclemastine transmitted in breast milk. Lancet 1982; I: 914–5

    Article  Google Scholar 

  131. Söderman P, Matheson I. Clonazepam in breast milk. Eur JPediatr 1988; 147: 212–3

    Article  Google Scholar 

  132. Fisher JB, Edgren BE, Mammel MC, et al. Neonatal apneaassociated with maternal clonazepam therapy: a case report.Obstet Gynecol 1985; 66(3 Suppl.): 34S–5S

    PubMed  CAS  Google Scholar 

  133. Schou M, Amdisen A. Lithium and pregnancy. III. Lithiumingestion by children breast-fed by woman on lithium treatment[letter]. BMJ 1973; 2: 138

    Article  PubMed  CAS  Google Scholar 

  134. Tunnesen WW, Hertz CG. Toxic effects of lithium in newborninfants: a commentary. J Pediatr 1972; 81: 804–7

    Article  Google Scholar 

  135. Weinstein M, Goldfield M. Lithium carbonate treatment duringpregnancy. Dis Nerv Syst 1969; 30: 828–32

    PubMed  CAS  Google Scholar 

  136. Sykes PA, Quarrie J, Alexander FW. Lithium carbonate andbreast-feeding [letter]. BMJ 1976; 4: 1299

    Article  Google Scholar 

  137. Von Unruh GE, Froescher W, Hoffman F, et al. Valproic acid inbreast milk: how much is really there? Ther Drug Monit 1984;6: 272–6

    Article  Google Scholar 

  138. Dickinson R, Harland RC, Lynn RK, et al. Transmission ofvalproic acid (Depakene) across the placenta: half-life of thedrag in mother and baby. J Pediatr 1979; 94: 832–5

    Article  PubMed  CAS  Google Scholar 

  139. Alexander FW. Sodium valproate and pregnancy [letter]. ArchDis Child 1979; 54: 240

    Article  CAS  Google Scholar 

  140. Nau H, Rating S, Koch S, et al. Valproic acid and its metabolites:placental transfer, neonatal pharmacokinetics, transfervia mothers milk and clinical status in neonates of epilepticmothers. J Pharmacol Exp Ther 1981; 219: 768–77

    PubMed  CAS  Google Scholar 

  141. Nau H, Helge H, Luck W. Valproic acid in the perinatal period:decreased maternal serum protein binding results in fetal accumulationand neonatal displacement of the drag and somemetabolites. J Pediatr 1984; 104: 627–34

    Article  PubMed  CAS  Google Scholar 

  142. Bardy AH, Granstrm ML, Hiilesmaa VK. Valproic acid andbreastfeeding. In: Janz D, et al, editors. Epilepsy, pregnancyand the child. New York: Raven Press, 1982: 359–60

    Google Scholar 

  143. Philbert A, Pedersen B, Dam M. Concentration of valproateduring pregnancy, in the newborn and in breast milk. ActaNeurol Scand 1985; 72: 460–3

    CAS  Google Scholar 

  144. Tsuru N, Maeda T, Tsuruoka M. Three cases of delivery undersodium valproate: placental transfer, milk transfer and probableteratogenicity of sodium valproate. Jpn J Psychiatry Neurol1988; 42: 89–96

    PubMed  CAS  Google Scholar 

  145. Skausig OB, Schou M. Breastfeeding during lithium treatment[in Danish]. Ugeskr Laeger 1977; 139: 400–1

    PubMed  CAS  Google Scholar 

  146. Amdisen A. Comment on: Evidence of an altered thyroid functionin man during treatment with lithium carbonate. ActaPsychiat Scand 1969; 45: Suppl. 207: 67

    Google Scholar 

  147. Anath J. Side effects in the neonate from psychotropic agentsexcreted through breastfeeding. Am J Psychiatry 1978; 135:801–5

    Google Scholar 

  148. Schou M, Amdisen MR. Problems of lithium maintenance treatmentduring pregnancy delivery and lactation. Agressologie1980; 21: A7–9

    Google Scholar 

  149. Rane A, Bertilsson L, Palmér L. Disposition of placentallytransferred carbamazepine (Tegretol) in the newborn. Eur JClin Pharmacol 1975; 82: 83–4

    Google Scholar 

  150. Frey B, Schubiger G, Musy JP. Transient cholestatic hepatitisin a neonate associated with carbamazepine exposure duringpregnancy and breast-feeding. Eur J Pediatr 1990; 150: 136–8

    Article  PubMed  CAS  Google Scholar 

  151. Goldberg HL. Psychotropic drugs in pregnancy and lactation.Int J Psychiatry Med 1994; 24: 129–47

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology, Norrland University Hospital, Umeå, Sweden

    Olav Spigset & Staffan Hägg

  2. Department of Clinical Pharmacology, Regional and University Hospital, N-7006, Trondheim, Norway

    Olav Spigset

Authors
  1. Olav Spigset
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Staffan Hägg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olav Spigset.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spigset, O., Hägg, S. Excretion of Psychotropic Drugs into Breast Milk. Mol Diag Ther 9, 111–134 (1998). https://doi.org/10.2165/00023210-199809020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199809020-00004

Keywords

Search

Navigation