Skip to main content
SpringerLink
Log in

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

  • Review
  • Published:
Archives of Women's Mental Health Aims and scope Submit manuscript

Summary

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.

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.

Similar content being viewed by others

References

  • J Allen D Hector (2005) ArticleTitleBenefits of breastfeeding New South Wales Public Health Bull 16 IssueID3–4 46

    Google Scholar 

  • LL Altshuler VK Burt M McMullen V Hendrick (1995) ArticleTitleBreastfeeding and sertraline: a 24-hour analysis J Clin Psychiatry 56 243–245 Occurrence Handle7775366 Occurrence Handle1:STN:280:DyaK2M3ptlyquw%3D%3D

    PubMed  CAS  Google Scholar 

  • InstitutionalAuthorNameAmerican Academy of Pediatrics (1997) ArticleTitleWork Group on Breastfeeding: Breastfeeding and the use of human milk Pediatrics 100 1035–1039 Occurrence Handle10.1542/peds.100.6.1035

    Article  Google Scholar 

  • HC Atkinson EJ Begg BA Darlow (1998) ArticleTitleDrugs in human milk: clinical pharmacokinetic consideration Clin Pharmacokinet 23 139–147

    Google Scholar 

  • CT Beck (2006) ArticleTitlePostpartum depression: it isn’t just the blues Am J Nurs 106 IssueID5 40–50

    Google Scholar 

  • EJ Begg HC Atkinson SB Duffull (1992) ArticleTitleProspective evaluation of a model for the prediction of milk: plasma drug concentrations from physicochemical characteristics J Clin Pharmacol 33 501–505 Occurrence Handle1:CAS:528:DyaK38XktF2rt7o%3D

    CAS  Google Scholar 

  • EJ Begg SB Duffull DA Saunders RC Buttimore KF Ilett LP Hackett P Yapp DA Wilson (1999) ArticleTitleParoxetine in human milk Br J Clin Pharmacol 48 142–147 Occurrence Handle10417489 Occurrence Handle10.1046/j.1365-2125.1999.00992.x Occurrence Handle1:CAS:528:DyaK1MXlslyjtbs%3D

    Article  PubMed  CAS  Google Scholar 

  • JØ Berle VM Steen TO Aamo H Breilid K Zahlsen O Spigset (2004) ArticleTitleBreastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypes J Clin Psychiatry 65 1228–1234 Occurrence Handle15367050 Occurrence Handle1:CAS:528:DC%2BD2cXptVegsLo%3D Occurrence Handle10.4088/JCP.v65n0911

    Article  PubMed  CAS  Google Scholar 

  • GG Briggs RK Freeman SJ Yaffe (1994) Drugs in pregnancy and lactation EditionNumber4 William and Wilkins Baltimore

    Google Scholar 

  • RJ Boerner HJ Möller (1999) ArticleTitleThe importance of new antidepressants in the treatment of anxiety/depressive disorders Pharmacopsychiatry 32 119–126 Occurrence Handle10505481 Occurrence Handle1:CAS:528:DyaK1MXmsFeju7o%3D

    PubMed  CAS  Google Scholar 

  • KJ Burch BG Wells (1992) ArticleTitleFluoxetine/norfluoxetine concentrations in human milk Pediatrics 88 676–677

    Google Scholar 

  • VK Burt R Suri L Altshuler ZN Stowe VC Hendrick E Muntean (2001) ArticleTitleThe use of psychotropic medications during breastfeeding Am J Psychiatry 158 1001–1009 Occurrence Handle11431219 Occurrence Handle10.1176/appi.ajp.158.7.1001 Occurrence Handle1:STN:280:DC%2BD3MznsVehug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • Citalopram. Drug Monograph. Available on: http://www.mentalhealth.com/drug/p30-c04.html. Accessed July 2, 2006.

  • CA Crisholm JA Kuller (1997) ArticleTitleA guide to the safety of CNS-active agents during breastfeeding Drug Saf 17 IssueID2 127–142

    Google Scholar 

  • S Dodd A Stocki A Buist GD Burrows K Maguire TR Norman (2000) ArticleTitleSertraline in paired blood plasma and breast-milk samples for nursing mothers Hum Psychopharmacol Clin Exper 15 261–264 Occurrence Handle1:CAS:528:DC%2BD3cXltFOmu7s%3D

    CAS  Google Scholar 

  • M Eberhard-Gran A Eskild A Opjordsmoen (2006) ArticleTitleUse of psychotropic medications in treating mood disorders during lactation: practical recommendations CNS Drugs 20 IssueID3 187–198 Occurrence Handle16529525 Occurrence Handle10.2165/00023210-200620030-00002 Occurrence Handle1:CAS:528:DC%2BD28XkvF2mtbw%3D

    Article  PubMed  CAS  Google Scholar 

  • Fluoxetine Drug Monograph. Available on: http://www_mentalhealth.com/drug/p30-p05.hclm. Accessed: July 2, 2006.

  • Fluvoxamine Drug Monograph. Available on: http://www.mentalhealth.com/drug/p30-l05.html. Accessed: July 2, 2006.

  • EJF Franssen V Meijs F Ettaher PG Valerio M Keesen W Lameijer (2006) ArticleTitleCitalopram serum and milk levels in mother and infant during lactation Ther Drug Monitor 28 2–4 Occurrence Handle10.1097/01.ftd.0000187972.02624.2e Occurrence Handle1:CAS:528:DC%2BD28XkvFKitQ%3D%3D

    Article  CAS  Google Scholar 

  • MP Freeman M Anthony (2004) ArticleTitleFocus on women’s mental health [Editorial] J Clin Psychiatry 65 1164–1165 Occurrence Handle15367041

    PubMed  Google Scholar 

  • S Gale BL Harlow (2003) ArticleTitlePostpartum mood disorder: a review of clinical and epidemiological factors J Psychosom Obstet Gynaecol 24 IssueID4 257–266 Occurrence Handle14702886 Occurrence Handle1:STN:280:DC%2BD2c%2FgsFygtQ%3D%3D Occurrence Handle10.3109/01674820309074690

    Article  PubMed  CAS  Google Scholar 

  • S Gentile (2005a) ArticleTitleSSRIs in pregnancy and lactation. Emphasis on neurodevelopmental outcome CNS Drugs 19 623–633 Occurrence Handle10.2165/00023210-200519070-00004 Occurrence Handle1:CAS:528:DC%2BD2MXpsFWkt7k%3D

    Article  CAS  Google Scholar 

  • S Gentile (2005b) ArticleTitleThe safety of newer antidepressants in pregnancy and breastfeeding Drug Safety 28 135–152 Occurrence Handle10.2165/00002018-200528020-00005

    Article  Google Scholar 

  • S Gentile (2007) ArticleTitleUse of contemporary antidepressants during breastfeeding. A proposal for a specific safety index Drug Saf 30 IssueID20 107–121 Occurrence Handle17253877 Occurrence Handle10.2165/00002018-200730020-00002 Occurrence Handle1:CAS:528:DC%2BD2sXivF2ks7o%3D

    Article  PubMed  CAS  Google Scholar 

  • GlaxoSmithKline. Paroxetine US Prescribing Information. Available on: http://GSK.com/products/assets/us_paxil.pdf. Accessed September 22, 2006.

  • S Hägg K Granberg L Carleborg (2000) ArticleTitleExcretion of fluvoxamine into breast milk [Letter] Br J Clin Pharmacol 49 286–287 Occurrence Handle10718788 Occurrence Handle10.1046/j.1365-2125.2000.00142-3.x

    Article  PubMed  Google Scholar 

  • TW Hale (2002) Medications and mother’s milk EditionNumber10 Pharmasoft Medical, Amarillo Texas

    Google Scholar 

  • TW Hale S Shum M Grossberg (2001) ArticleTitleFluoxetine toxicity in a breastfed infant Clin Pediatrics 40 681–684 Occurrence Handle1:STN:280:DC%2BD38%2FksVGjtQ%3D%3D

    CAS  Google Scholar 

  • T Heikkinen U Ekblad P Kero S Ekblad K Laine (2002) ArticleTitleCitalopram in pregnancy and lactation Clin Pharmacol Ther 72 184–191 Occurrence Handle12189365 Occurrence Handle10.1067/mcp.2002.126181 Occurrence Handle1:CAS:528:DC%2BD38Xnt1aqtLw%3D

    Article  PubMed  CAS  Google Scholar 

  • T Heikkinen U Ekblad P Palo K Laine (2003) ArticleTitlePharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation Clin Pharmacol Ther 73 330–337 Occurrence Handle12709723 Occurrence Handle10.1016/S0009-9236(02)17634-X Occurrence Handle1:CAS:528:DC%2BD3sXjtFWntb8%3D

    Article  PubMed  CAS  Google Scholar 

  • V Hendrick ZN Stowe LL Altshuler L Lori A Hostetter A Fukuchi (2000) ArticleTitleParoxetine use during breastfeeding [Letter] J Clin Psychopharmacol 20 587–589 Occurrence Handle11001251 Occurrence Handle10.1097/00004714-200010000-00022 Occurrence Handle1:STN:280:DC%2BD3cvkvVagtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • V Hendrick ZN Stowe LL Altshuler J Mintz S Hwang A Hostetter et al. (2001) ArticleTitleFluoxetine and norfluoxetine concentrations in nursing infants and breast milk Biol Psychiatry 50 775–782 Occurrence Handle11720696 Occurrence Handle10.1016/S0006-3223(01)01197-0 Occurrence Handle1:CAS:528:DC%2BD3MXosFKksr0%3D

    Article  PubMed  CAS  Google Scholar 

  • KE Isenberg (1990) ArticleTitleExcretion of fluoxetine in human breast milk [Letter] J Clin Psychiatry 51 169 Occurrence Handle2324084 Occurrence Handle1:STN:280:DyaK3c3hs1Kmsg%3D%3D

    PubMed  CAS  Google Scholar 

  • S Ito (2000) ArticleTitleDrug therapy for breast-feeding infants New Engl J Med 343 118–127 Occurrence Handle10891521 Occurrence Handle10.1056/NEJM200007133430208 Occurrence Handle1:CAS:528:DC%2BD3cXltlKqs7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • PN Jensen OV Olesen A Bertelsen K Linnet (1997) ArticleTitleCitalopram and desmethylcitalopram concentrations in breast milk and in serum of mother and infant Ther Drug Monitor 19 236–239 Occurrence Handle10.1097/00007691-199704000-00021 Occurrence Handle1:STN:280:DyaK2s3mt1aktg%3D%3D

    Article  CAS  Google Scholar 

  • J Kim KW Riggs S Misri N Kent TF Oberlander RE Grunau et al. (2005) ArticleTitleStereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breastfeeding Br J Clin Pharmacolol 61 155–163 Occurrence Handle10.1111/j.1365-2125.2005.02538.x Occurrence Handle1:CAS:528:DC%2BD28XitFOqu70%3D

    Article  CAS  Google Scholar 

  • JH Kristensen KF Ilett LJ Dusci LP Hackett P Yapp RE Wojnar-Horton et al. (1998) ArticleTitleDistribution and excretion of sertraline and N-desmethylsertraline in human milk Br J Clin Pharmacol 45 453–457 Occurrence Handle9643617 Occurrence Handle10.1046/j.1365-2125.1998.00705.x Occurrence Handle1:CAS:528:DyaK1cXjslGgtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • JH Kristensen KF Ilett LP Hackett P Yapp M Paech EJ Begg (1999) ArticleTitleDistribution and excretion of fluoxetine and norfluoxetine in human milk Br J Clin Pharmacol 48 521–527 Occurrence Handle10583022 Occurrence Handle10.1046/j.1365-2125.1999.00040.x Occurrence Handle1:CAS:528:DyaK1MXmvFalu7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • JH Kristensen PL Hackett R Kohan M Paech KF Ilett (2002) ArticleTitleThe amount of fluvoxamine in milk is unlikely to be a cause of adverse effects in breastfed infants J Hum Lactat 18 139–143

    Google Scholar 

  • LA Larsen S Ito G Koren (2003) ArticleTitlePrediction of milk/plasma ratio of drugs Ann Pharmacother 37 IssueID9 1299–1306 Occurrence Handle12921514 Occurrence Handle10.1345/aph.1C379 Occurrence Handle1:CAS:528:DC%2BD3sXnsFCms7s%3D

    Article  PubMed  CAS  Google Scholar 

  • Lexa Lexapro FAQs. Available on: http://www.lexapro.com/english/faq/currently_taking.aspx#qo12. Accessed July 2, 2006.

  • K Malone K Papagni S Ramini NL Keltner (2004) ArticleTitleAntidepressants, antipsychotics, benzodiazepines, and the breastfeeding dyad Perspect Psych Care 40 73–85 Occurrence Handle10.1111/j.1744-6163.2004.00073.x

    Article  Google Scholar 

  • RM Martin N Middleton D Gunnell CG Owen GD Smith (2005) ArticleTitleBreast-feeding and cancer: the Body Orr cohort and a systematic review with meta-analysis J Natl Cancer Inst 97 1446–1457 Occurrence Handle16204694

    PubMed  Google Scholar 

  • S Misri J Kim K Riggs X Kostaras (2000) ArticleTitleParoxetine levels in postpartum depressed women, breast milk, and infant serum J Clin Psychiatry 61 828–832 Occurrence Handle11105735 Occurrence Handle1:CAS:528:DC%2BD3cXovVGgtbo%3D

    PubMed  CAS  Google Scholar 

  • I Öhman B Wikner-Norsted S Vitols (1997) ArticleTitleCitalopram and metabolite levels in plasma and breast milk in two nursing women [Abstract] Eur J Clin Pharmacol 52 IssueIDSuppl A179

    Google Scholar 

  • R Öhman S Hägg L Carleborg O Spigset (1999) ArticleTitleExcretion of paroxetine into breast milk J Clin Psychiatry 60 519–523 Occurrence Handle10485633

    PubMed  Google Scholar 

  • Pediatric Pharmacotherapy (1996) Determining the degree of drug transfer. Available on: www.healthsystem.virginia.edu/internet/pediatrics/pharma-news/April96.PDF.

  • G Pons E Rey I Matheson (1994) ArticleTitleExcretion of psychoactive drugs into breast milk Clin Pharmacokin 27 270–289 Occurrence Handle1:CAS:528:DyaK2MXitFSru7c%3D

    CAS  Google Scholar 

  • J Rampono JH Kristensen LP Hackett M Paech R Kohan KF Ilett (2000) ArticleTitleCitalopram and demethylcitalopram in human milk; distribution, excretion and effects in breast fed infants Br J Clin Pharmacol 50 263–268 Occurrence Handle10971311 Occurrence Handle10.1046/j.1365-2125.2000.00253.x Occurrence Handle1:CAS:528:DC%2BD3cXnt1Kgur8%3D

    Article  PubMed  CAS  Google Scholar 

  • J Rampono LP Hackett JH Kristensen R Kohan M Page-Sharp KF Ilett (2006) ArticleTitleTransfer of escitalopram and its metabolite demethylescitalopram into breast milk Br J Clin Pharmacol 62 IssueID3 316–322 Occurrence Handle16934048 Occurrence Handle10.1111/j.1365-2125.2006.02659.x Occurrence Handle1:CAS:528:DC%2BD28XhtVGms7vL

    Article  PubMed  CAS  Google Scholar 

  • T Riman PW Dickman S Nilsson N Correia H Nordlinder CM Magnusson et al. (2004) ArticleTitleRisk factors for invasive epithelial ovarian cancer: results from a Swedish case-control study Am J Epidemiol 156 763–773

    Google Scholar 

  • K Schmidt OV Olesen PN Jensen (2000) ArticleTitleCitalopram and breast-feeding: serum concentration and side effects in the infant Biol Psychiatry 47 164–165 Occurrence Handle10664835 Occurrence Handle10.1016/S0006-3223(99)00155-9 Occurrence Handle1:CAS:528:DC%2BD3cXosVansg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • Sertraline. Drug Monograph. Available on: http://www.mentalhealth.com/drug/p30-z02.html. Accessed: July 2, 2006.

  • O Spigset L Carleborg Å Norström M Sandlund (1996) ArticleTitleParoxetine levels in breast milk [Letter] J Clin Psychiatry 57 39 Occurrence Handle8543546 Occurrence Handle1:STN:280:DyaK287kt1ahug%3D%3D

    PubMed  CAS  Google Scholar 

  • O Spigset L Carleborg R Öhman Å Noström (1997) ArticleTitleExcretion of citalopram in breast milk Br J Clin Pharmacol 44 295–298 Occurrence Handle9296327 Occurrence Handle10.1046/j.1365-2125.1997.t01-1-00576.x Occurrence Handle1:CAS:528:DyaK2sXmtVChu7s%3D

    Article  PubMed  CAS  Google Scholar 

  • ZN Stowe MJ Owens JC Landry CD Kilts T Ely A Llewellyn et al. (1997) ArticleTitleSertraline and desmethylsertraline in human breast milk and nursing infants Am J Psychiatry 154 1255–1260 Occurrence Handle9286185 Occurrence Handle1:STN:280:DyaK2svjt1artA%3D%3D

    PubMed  CAS  Google Scholar 

  • ZN Stowe LS Cohen A Hostetter JC Ritchie MJ Owens CB Nemeroff (2000) ArticleTitleParoxetine in human breast milk and nursing infants Am J Psychiatry 157 185–189 Occurrence Handle10671385 Occurrence Handle10.1176/appi.ajp.157.2.185 Occurrence Handle1:STN:280:DC%2BD3c7jslKrug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • ZN Stowe AL Hostetter MJ Owens JC Ritchie K Stemberg LS Cohen et al. (2003) ArticleTitleThe pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations J Clin Psychiatry 64 73–80 Occurrence Handle12590627 Occurrence Handle1:CAS:528:DC%2BD3sXhs1Wmurk%3D Occurrence Handle10.4088/JCP.v64n0114

    Article  PubMed  CAS  Google Scholar 

  • R Suri ZN Stowe V Hendrick A Hostetter M Widawski LL Altshuler (2002) ArticleTitleEstimates of nursing infant daily dose of fluoxetine through breast milk Biol Psychiatry 52 446–451 Occurrence Handle12242061 Occurrence Handle10.1016/S0006-3223(02)01368-9 Occurrence Handle1:CAS:528:DC%2BD38XntVWrs70%3D

    Article  PubMed  CAS  Google Scholar 

  • Texas Tech University. Mechanisms of Drug Entry into Human Milk. Available on: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9233209&dopt=Abstract. Accessed: July 2, 2006.

  • M Wadelius E Darj G Frenne A Rane (1997) ArticleTitleInduction of CYP2D6 in pregnancy Clin Pharmacol Ther 26 400–407

    Google Scholar 

  • A Warner (1986) ArticleTitleDrug use in the neonate: interrelationships of pharmacokinetics, toxicity, and biochemical maturity Clin Chemistry 32 721–727 Occurrence Handle1:CAS:528:DyaL28XitFynu7g%3D

    CAS  Google Scholar 

  • AM Weissman BT Levy AJ Hartz S Bentler M Donohue VL Ellingrod et al. (2004) ArticleTitlePooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants Am J Psychiatry 161 1066–1078 Occurrence Handle15169695 Occurrence Handle10.1176/appi.ajp.161.6.1066

    Article  PubMed  Google Scholar 

  • DH Whitby KL Smith (2005) ArticleTitleThe use of tricyclic antidepressants and selective serotonin reuptake inhibitors in women who are breastfeeding Pharmacother 25 411–425 Occurrence Handle10.1592/phco.25.3.411.61597 Occurrence Handle1:CAS:528:DC%2BD2MXisFSjtbc%3D

    Article  CAS  Google Scholar 

  • KL Wisner BL Parry CM Piontek (2002) ArticleTitlePostpartum depression New Engl J Med 347 194–199 Occurrence Handle12124409 Occurrence Handle10.1056/NEJMcp011542

    Article  PubMed  Google Scholar 

  • AW Wolf I De Andraca B Lozoff (2002) ArticleTitleMaternal depression in three Latin American samples Soc Psychiatry Psychiatr Epidemiol 37 169–176 Occurrence Handle12027243 Occurrence Handle10.1007/s001270200011

    Article  PubMed  Google Scholar 

  • S Wright S Dawling JJ Ashford (1991) ArticleTitleExcretion of fluvoxamine in breast milk [Letter] Br J Clin Pharmacolol 31 209 Occurrence Handle1:STN:280:DyaK3M3msFahtA%3D%3D

    CAS  Google Scholar 

  • K Yoshida B Smith R Channi Kumar (1997) ArticleTitleFluvoxamine in breast milk and infant development [Letter] Br J Clin Pharmacolol 44 210–211 Occurrence Handle1:CAS:528:DyaK2sXls1WrsLw%3D

    CAS  Google Scholar 

  • K Yoshida B Smith M Craggs R Channi Kumar (1998) ArticleTitleFluoxetine in breast-milk and developmental outcome of breast-fed infants Br J Psychiatry 172 175–179 Occurrence Handle9519072 Occurrence Handle1:STN:280:DyaK1c7nvFGqtA%3D%3D Occurrence Handle10.1192/bjp.172.2.175

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Mental Health ASL Salerno 1, Mental Health Center n.4, Cava de’ Tirreni (Salerno), Italy

    S. Gentile

  2. Medical Department Eli Lilly Italia, Sesto Fiorentino (FI), Italy

    A. Rossi

  3. Section of Psychiatry and Clinical Psychology, Department of Medicine and Public Health, University of Verona, Verona, Italy

    C. Bellantuono

Authors
  1. S. Gentile
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Bellantuono
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gentile, S., Rossi, A. & Bellantuono, C. SSRIs during breastfeeding: spotlight on milk-to-plasma ratio. Arch Womens Ment Health 10, 39–51 (2007). https://doi.org/10.1007/s00737-007-0173-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00737-007-0173-0

Search

Navigation