Archives of Women's Mental Health

, Volume 10, Issue 2, pp 39–51 | Cite as

SSRIs during breastfeeding: spotlight on milk-to-plasma ratio

  • S. Gentile
  • A. Rossi
  • C. Bellantuono


Objective: To investigate the usefulness of the milk-to-plasma (M/P) ratio for assessing the risks for the breastfed infant associated with the maternal use of SSRIs.

Data sources: Medline, Toxnet, Embase, Current Contents, and PsycInfo indexed articles from 1980 to September 2006.

Study selection and data extraction: All studies reporting the M/P ratio in mothers taking SSRIs while breastfeeding or studies which such an information could be calculated from data reported in the article.

Data synthesis: Higher M/P ratios were rarely associated with a clinically significant impact on the babies during the early phases of breastfeeding.

Conclusions: So far no evidence-based information seems to support the hypothesis that SSRIs characterized by a M/P ratio <1.0 should be preferred. Hence, physicians should consider different parameters when attempting to choose the safest SSRI for the breastfeeding woman. These parameters might be represented by the number of well-documented published adverse event reports and the tendency of each SSRI of inducing in the infants serum concentrations that are elevated above 10% of average maternal serum levels. In any case, if the mother wishes to breastfeed her infant while taking a SSRI, the baby should be closely monitored in order to promptly detect any iatrogenic event.

Keywords: Breastfeeding; lactation; milk/plasma ratio; safety; SSRIs. 


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  1. Allen, J, Hector, D 2005Benefits of breastfeedingNew South Wales Public Health Bull1646Google Scholar
  2. Altshuler, LL, Burt, VK, McMullen, M, Hendrick, V 1995Breastfeeding and sertraline: a 24-hour analysisJ Clin Psychiatry56243245PubMedGoogle Scholar
  3. American Academy of Pediatrics1997Work Group on Breastfeeding: Breastfeeding and the use of human milkPediatrics10010351039CrossRefGoogle Scholar
  4. Atkinson, HC, Begg, EJ, Darlow, BA 1998Drugs in human milk: clinical pharmacokinetic considerationClin Pharmacokinet23139147Google Scholar
  5. Beck, CT 2006Postpartum depression: it isn’t just the bluesAm J Nurs1064050Google Scholar
  6. Begg, EJ, Atkinson, HC, Duffull, SB 1992Prospective evaluation of a model for the prediction of milk: plasma drug concentrations from physicochemical characteristicsJ Clin Pharmacol33501505Google Scholar
  7. Begg, EJ, Duffull, SB, Saunders, DA, Buttimore, RC, Ilett, KF, Hackett, LP, Yapp, P, Wilson, DA 1999Paroxetine in human milkBr J Clin Pharmacol48142147PubMedCrossRefGoogle Scholar
  8. Berle, JØ, Steen, VM, Aamo, TO, Breilid, H, Zahlsen, K, Spigset, O 2004Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypesJ Clin Psychiatry6512281234PubMedCrossRefGoogle Scholar
  9. Briggs, GG, Freeman, RK, Yaffe, SJ 1994Drugs in pregnancy and lactation4William and WilkinsBaltimoreGoogle Scholar
  10. Boerner, RJ, Möller, HJ 1999The importance of new antidepressants in the treatment of anxiety/depressive disordersPharmacopsychiatry32119126PubMedGoogle Scholar
  11. Burch, KJ, Wells, BG 1992Fluoxetine/norfluoxetine concentrations in human milkPediatrics88676677Google Scholar
  12. Burt, VK, Suri, R, Altshuler, L, Stowe, ZN, Hendrick, VC, Muntean, E 2001The use of psychotropic medications during breastfeedingAm J Psychiatry15810011009PubMedCrossRefGoogle Scholar
  13. Citalopram. Drug Monograph. Available on: Accessed July 2, 2006.
  14. Crisholm, CA, Kuller, JA 1997A guide to the safety of CNS-active agents during breastfeedingDrug Saf17127142Google Scholar
  15. Dodd, S, Stocki, A, Buist, A, Burrows, GD, Maguire, K, Norman, TR 2000Sertraline in paired blood plasma and breast-milk samples for nursing mothersHum Psychopharmacol Clin Exper15261264Google Scholar
  16. Eberhard-Gran, M, Eskild, A, Opjordsmoen, A 2006Use of psychotropic medications in treating mood disorders during lactation: practical recommendationsCNS Drugs20187198PubMedCrossRefGoogle Scholar
  17. Fluoxetine Drug Monograph. Available on: Accessed: July 2, 2006.
  18. Fluvoxamine Drug Monograph. Available on: Accessed: July 2, 2006.
  19. Franssen, EJF, Meijs, V, Ettaher, F, Valerio, PG, Keesen, M, Lameijer, W 2006Citalopram serum and milk levels in mother and infant during lactationTher Drug Monitor2824CrossRefGoogle Scholar
  20. Freeman, MP, Anthony, M 2004Focus on women’s mental health [Editorial]J Clin Psychiatry6511641165PubMedGoogle Scholar
  21. Gale, S, Harlow, BL 2003Postpartum mood disorder: a review of clinical and epidemiological factorsJ Psychosom Obstet Gynaecol24257266PubMedCrossRefGoogle Scholar
  22. Gentile, S 2005aSSRIs in pregnancy and lactation. Emphasis on neurodevelopmental outcomeCNS Drugs19623633CrossRefGoogle Scholar
  23. Gentile, S 2005bThe safety of newer antidepressants in pregnancy and breastfeedingDrug Safety28135152CrossRefGoogle Scholar
  24. Gentile, S 2007Use of contemporary antidepressants during breastfeeding. A proposal for a specific safety indexDrug Saf30107121PubMedCrossRefGoogle Scholar
  25. GlaxoSmithKline. Paroxetine US Prescribing Information. Available on: Accessed September 22, 2006.
  26. Hägg, S, Granberg, K, Carleborg, L 2000Excretion of fluvoxamine into breast milk [Letter]Br J Clin Pharmacol49286287PubMedCrossRefGoogle Scholar
  27. Hale, TW 2002Medications and mother’s milk10Pharmasoft Medical, AmarilloTexasGoogle Scholar
  28. Hale, TW, Shum, S, Grossberg, M 2001Fluoxetine toxicity in a breastfed infantClin Pediatrics40681684Google Scholar
  29. Heikkinen, T, Ekblad, U, Kero, P, Ekblad, S, Laine, K 2002Citalopram in pregnancy and lactationClin Pharmacol Ther72184191PubMedCrossRefGoogle Scholar
  30. Heikkinen, T, Ekblad, U, Palo, P, Laine, K 2003Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactationClin Pharmacol Ther73330337PubMedCrossRefGoogle Scholar
  31. Hendrick, V, Stowe, ZN, Altshuler, LL, Lori, L, Hostetter, A, Fukuchi, A 2000Paroxetine use during breastfeeding [Letter]J Clin Psychopharmacol20587589PubMedCrossRefGoogle Scholar
  32. Hendrick, V, Stowe, ZN, Altshuler, LL, Mintz, J, Hwang, S, Hostetter, A,  et al. 2001Fluoxetine and norfluoxetine concentrations in nursing infants and breast milkBiol Psychiatry50775782PubMedCrossRefGoogle Scholar
  33. Isenberg, KE 1990Excretion of fluoxetine in human breast milk [Letter]J Clin Psychiatry51169PubMedGoogle Scholar
  34. Ito, S 2000Drug therapy for breast-feeding infantsNew Engl J Med343118127PubMedCrossRefGoogle Scholar
  35. Jensen, PN, Olesen, OV, Bertelsen, A, Linnet, K 1997Citalopram and desmethylcitalopram concentrations in breast milk and in serum of mother and infantTher Drug Monitor19236239CrossRefGoogle Scholar
  36. Kim, J, Riggs, KW, Misri, S, Kent, N, Oberlander, TF, Grunau, RE,  et al. 2005Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breastfeedingBr J Clin Pharmacolol61155163CrossRefGoogle Scholar
  37. Kristensen, JH, Ilett, KF, Dusci, LJ, Hackett, LP, Yapp, P, Wojnar-Horton, RE,  et al. 1998Distribution and excretion of sertraline and N-desmethylsertraline in human milkBr J Clin Pharmacol45453457PubMedCrossRefGoogle Scholar
  38. Kristensen, JH, Ilett, KF, Hackett, LP, Yapp, P, Paech, M, Begg, EJ 1999Distribution and excretion of fluoxetine and norfluoxetine in human milkBr J Clin Pharmacol48521527PubMedCrossRefGoogle Scholar
  39. Kristensen, JH, Hackett, PL, Kohan, R, Paech, M, Ilett, KF 2002The amount of fluvoxamine in milk is unlikely to be a cause of adverse effects in breastfed infantsJ Hum Lactat18139143Google Scholar
  40. Larsen, LA, Ito, S, Koren, G 2003Prediction of milk/plasma ratio of drugsAnn Pharmacother3712991306PubMedCrossRefGoogle Scholar
  41. Lexa Lexapro FAQs. Available on: Accessed July 2, 2006.
  42. Malone, K, Papagni, K, Ramini, S, Keltner, NL 2004Antidepressants, antipsychotics, benzodiazepines, and the breastfeeding dyadPerspect Psych Care407385CrossRefGoogle Scholar
  43. Martin, RM, Middleton, N, Gunnell, D, Owen, CG, Smith, GD 2005Breast-feeding and cancer: the Body Orr cohort and a systematic review with meta-analysisJ Natl Cancer Inst9714461457PubMedGoogle Scholar
  44. Misri, S, Kim, J, Riggs, K, Kostaras, X 2000Paroxetine levels in postpartum depressed women, breast milk, and infant serumJ Clin Psychiatry61828832PubMedGoogle Scholar
  45. Öhman, I, Wikner-Norsted, B, Vitols, S 1997Citalopram and metabolite levels in plasma and breast milk in two nursing women [Abstract]Eur J Clin Pharmacol52A179Google Scholar
  46. Öhman, R, Hägg, S, Carleborg, L, Spigset, O 1999Excretion of paroxetine into breast milkJ Clin Psychiatry60519523PubMedGoogle Scholar
  47. Pediatric Pharmacotherapy (1996) Determining the degree of drug transfer. Available on:
  48. Pons, G, Rey, E, Matheson, I 1994Excretion of psychoactive drugs into breast milkClin Pharmacokin27270289Google Scholar
  49. Rampono, J, Kristensen, JH, Hackett, LP, Paech, M, Kohan, R, Ilett, KF 2000Citalopram and demethylcitalopram in human milk; distribution, excretion and effects in breast fed infantsBr J Clin Pharmacol50263268PubMedCrossRefGoogle Scholar
  50. Rampono, J, Hackett, LP, Kristensen, JH, Kohan, R, Page-Sharp, M, Ilett, KF 2006Transfer of escitalopram and its metabolite demethylescitalopram into breast milkBr J Clin Pharmacol62316322PubMedCrossRefGoogle Scholar
  51. Riman, T, Dickman, PW, Nilsson, S, Correia, N, Nordlinder, H, Magnusson, CM,  et al. 2004Risk factors for invasive epithelial ovarian cancer: results from a Swedish case-control studyAm J Epidemiol156763773Google Scholar
  52. Schmidt, K, Olesen, OV, Jensen, PN 2000Citalopram and breast-feeding: serum concentration and side effects in the infantBiol Psychiatry47164165PubMedCrossRefGoogle Scholar
  53. Sertraline. Drug Monograph. Available on: Accessed: July 2, 2006.
  54. Spigset, O, Carleborg, L, Norström, Å, Sandlund, M 1996Paroxetine levels in breast milk [Letter]J Clin Psychiatry5739PubMedGoogle Scholar
  55. Spigset, O, Carleborg, L, Öhman, R, Noström, Å 1997Excretion of citalopram in breast milkBr J Clin Pharmacol44295298PubMedCrossRefGoogle Scholar
  56. Stowe, ZN, Owens, MJ, Landry, JC, Kilts, CD, Ely, T, Llewellyn, A,  et al. 1997Sertraline and desmethylsertraline in human breast milk and nursing infantsAm J Psychiatry15412551260PubMedGoogle Scholar
  57. Stowe, ZN, Cohen, LS, Hostetter, A, Ritchie, JC, Owens, MJ, Nemeroff, CB 2000Paroxetine in human breast milk and nursing infantsAm J Psychiatry157185189PubMedCrossRefGoogle Scholar
  58. Stowe, ZN, Hostetter, AL, Owens, MJ, Ritchie, JC, Stemberg, K, Cohen, LS,  et al. 2003The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrationsJ Clin Psychiatry647380PubMedCrossRefGoogle Scholar
  59. Suri, R, Stowe, ZN, Hendrick, V, Hostetter, A, Widawski, M, Altshuler, LL 2002Estimates of nursing infant daily dose of fluoxetine through breast milkBiol Psychiatry52446451PubMedCrossRefGoogle Scholar
  60. Texas Tech University. Mechanisms of Drug Entry into Human Milk. Available on: Accessed: July 2, 2006.
  61. Wadelius, M, Darj, E, Frenne, G, Rane, A 1997Induction of CYP2D6 in pregnancyClin Pharmacol Ther26400407Google Scholar
  62. Warner, A 1986Drug use in the neonate: interrelationships of pharmacokinetics, toxicity, and biochemical maturityClin Chemistry32721727Google Scholar
  63. Weissman, AM, Levy, BT, Hartz, AJ, Bentler, S, Donohue, M, Ellingrod, VL,  et al. 2004Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infantsAm J Psychiatry16110661078PubMedCrossRefGoogle Scholar
  64. Whitby, DH, Smith, KL 2005The use of tricyclic antidepressants and selective serotonin reuptake inhibitors in women who are breastfeedingPharmacother25411425CrossRefGoogle Scholar
  65. Wisner, KL, Parry, BL, Piontek, CM 2002Postpartum depressionNew Engl J Med347194199PubMedCrossRefGoogle Scholar
  66. Wolf, AW, De Andraca, I, Lozoff, B 2002Maternal depression in three Latin American samplesSoc Psychiatry Psychiatr Epidemiol37169176PubMedCrossRefGoogle Scholar
  67. Wright, S, Dawling, S, Ashford, JJ 1991Excretion of fluvoxamine in breast milk [Letter]Br J Clin Pharmacolol31209Google Scholar
  68. Yoshida, K, Smith, B, Channi Kumar, R 1997Fluvoxamine in breast milk and infant development [Letter]Br J Clin Pharmacolol44210211Google Scholar
  69. Yoshida, K, Smith, B, Craggs, M, Channi Kumar, R 1998Fluoxetine in breast-milk and developmental outcome of breast-fed infantsBr J Psychiatry172175179PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • S. Gentile
    • 1
  • A. Rossi
    • 2
  • C. Bellantuono
    • 3
  1. 1.Department of Mental Health ASL Salerno 1Mental Health Center n.4, Cava de’ Tirreni (Salerno)Italy
  2. 2.Medical Department Eli Lilly ItaliaSesto Fiorentino (FI)Italy
  3. 3.Section of Psychiatry and Clinical Psychology, Department of Medicine and Public HealthUniversity of VeronaVeronaItaly

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