Clinical Lactation Studies of Lithium: A Systematic Review

Abstract

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 breast milk concentration was 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). 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.

Bipolar disorder: Treatment strategies for women of childbearing age

“…35 Lithium is excreted through breast milk, and it may be safer for postpartum women to feed via bottle rather than breastfeed. 36…”

“…Should the risks of lithium discontinuation outweigh the benefit in women pregnant or trying to become pregnant, careful monitoring of lithium serum levels should ensue, due to the potential risk of dehydration during pregnancy and subsequent lithium toxicity 35 . Lithium is excreted through breast milk, and it may be safer for postpartum women to feed via bottle rather than breastfeed 36 …”

Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series

“…The American Academy of Pediatrics (AAP), 2012 recommend exclusive breastfeeding for the first 6 months of life whenever possible, before combining it with complementary foods until the infant is 1–2 years old. Two recent systematic reviews of clinical studies into lithium use during breastfeeding found limited evidence about whether one should initiate, maintain, or discontinue lithium during breastfeeding ( Imaz et al, 2019 ; Newmark et al, 2019 ).…”

Neonatal Feeding Trajectories in Mothers With Bipolar Disorder Taking Lithium: Pharmacokinetic Data

“…Due to the very low molecular weight and lack of protein binding, lithium is readily transferred to breastmilk ( Hale and Rowe, 2017 ). Lithium excreted in human breast milk is highly variable, being approximately 50% (range 0.17–1.07%) of the mother serum concentration ( Imaz et al, 2019 ; Newmark et al, 2019 ). The amount of lithium that receives the infant depends on several factors, such as the volume of milk transfer to the infant, the concentration of the lithium in the milk, and the infant’s ability to absorb ( Lawrence, 1994 ).…”

“…Lithium use while breastfeeding is a controversial topic, due to the potential risk to the neonate of lithium accumulation and secondary toxicity, especially among those who are preterm and sick ( Malhi et al, 2017 ; Galbally et al, 2018 ). Two systematic reviews of clinical studies into lithium use during breastfeeding found limited evidence about whether one should initiate, maintain, or discontinue lithium during breastfeeding ( Imaz et al, 2019 ; Newmark et al, 2019 ).…”