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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01005

Clinical lactation studies of lithium: a systematic review

Maria Luisa Imaz1, Merce Torra1, Dolors Soy1, Luisa Garcia-Esteve1 and  Rocio Martin-Santos2*
  • 1Hospital Clínic de Barcelona, Spain
  • 2CIBERSAM, Hospital Clínic de Barcelona, Spain

Background: There is substantial evidence that postpartum prophylaxis with lithium lowers the rate of relapse in bipolar disorder. However, it is contraindicated during breastfeeding due to the high variability of the transfer into breast milk.
Aims: We conducted a systematic review of the current evidence of studies assessing the transfer of lithium to lactating infants and short-term infant outcomes.
Methods: An a priori protocol was designed based on PRISMA guidelines. Searches in Pubmed and LactMed were conducted until September 2018. Studies assessing lithium pharmacokinetic parameters and short-term infant outcomes were included. Quality was assessed using a checklist based on international guidelines (i.e FDA).
Results: From 344 initial studies, 13 case reports/series with 39 mother-child dyads were included. Only 15% of studies complied with ≥50% of the items on the quality assessment checklist. Infants breastfeed a mean (SD) of 58.9 (83.3) days. Mean maternal lithium dose was 904(293) mg/day; corresponding lithium plasma/serum concentration was 0.73(0.26) mEq/L and breastmilk concentration 0.84(0.14) mEq/L. Mean infant lithium plasma/serum concentration was 0.23(0.26) mEq/L. Twenty-six (80%) infants had concentrations ≤0.30 mEq/l without adverse effects. Eight (20%) showed a transient adverse event (i.e. acute toxicity or thyroid alterations), and two (5%) congenital malformations (cardiovascular and reproductive systems). All of them were also prenatally exposed to lithium monotherapy or polytherapy.
Conclusion: The current evidence comes from studies with a degree of heterogeneity and of low-moderate quality. However, it identifies areas of improvement for future clinical lactation studies of lithium and provides support for some clinical recommendations.

Keywords: Pharmacokinetics -, Systematic review, Nursing infants, neonate, Puerperium, Postpartum, Lactation, breastfeeding, Lithium

Received: 23 Apr 2019; Accepted: 08 Aug 2019.

Edited by:

Brian Godman, Karolinska Institute (KI), Sweden

Reviewed by:

Maria M. Salazar-Bookaman, Central University of Venezuela, Venezuela
Marianne Van-de-l'Isle, NHS Lothian, University of Edinburgh, United Kingdom  

Copyright: © 2019 Imaz, Torra, Soy, Garcia-Esteve and Martin-Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rocio Martin-Santos, Hospital Clínic de Barcelona, CIBERSAM, Barcelona, Spain,