Lithium use while Breastfeeding

Drugs containing Lithium: Lithium Carbonate ER, Lithobid, Eskalith, Lithonate, Eskalith-CR, Lithotabs

Lithium Levels and Effects while Breastfeeding

Summary of Use during Lactation

Although lithium appears on many lists of drugs contraindicated during breastfeeding, other sources do not consider it a contraindication, especially in infants over 2 months of age and during lithium monotherapy. Numerous reports exist of infants who were breastfed during maternal lithium therapy without any signs of toxicity or developmental problems. Most were breastfed from birth and some continued to nurse for up to 1 year of maternal lithium therapy. Limited data suggest that lithium in milk can adversely affect the infant when its elimination is impaired, as in dehydration or in newborn or premature infants. Neonates may also have transplacentally acquired serum lithium levels. The long-term effects of lithium on infants are not known, but limited data indicate no obvious problems in growth and development.[1]

Lithium may be used in mothers of fullterm infants who are willing and able to monitor their infants. Discontinuing lithium 24 to 48 hours before Cesarean section delivery or at the onset of spontaneous labor and resuming the prepregnancy lithium dose immediately after delivery should minimize the infant's serum lithium concentration at birth.[2] Some investigators recommend monitoring infant serum lithium, serum creatinine, BUN, and TSH every 4 to 12 weeks during breastfeeding and maternal lithium therapy.[3][4] However, others recommend close pediatric follow-up of the infant and only selective laboratory monitoring as clinically indicated.[2] Breastfeeding should be discontinued immediately and the infant evaluated if the infant appears restless or lethargic or has feeding problems.[2]

Drug Levels

Maternal Levels. Most older reports of lithium levels in breastmilk did not characterized breastmilk lithium excretion in a rigorous manner. Random milk levels have been reported to range from 0.12 to 0.7 mEq/L and appear to be rather consistent at about 40 to 45% of the simultaneous maternal serum level.[5][6][7][8] The milk concentration of lithium in one woman was found to be inversely proportional to milk volume. The milk to plasma ratio was found to be directly proportional to serum lithium; the ratio was about 1 with low serum lithium and 1.5 with higher serum lithium levels, indicating disproportionately higher lithium excretion into milk with higher serum levels.[9]

From data in papers published up to 1990 concerning 6 infants, it is estimated that a fully breastfed infant would receive about 26% (range 11 to 42%) of the maternal weight-adjusted dosage of lithium.[6][7][8][9][10][11]

A more recent case series of 11 mothers found the average infant dosage to be 12.2% (range 0 to 30%) of the maternal weight-adjusted dosage.[12] The reason for the difference between the older and more recent data is not apparent.

A case series reported 10 mothers taking lithium carbonate in an average daily dosage of 850 mg (range 600 to 1200 mg daily) for bipolar disorder. Lithium milk levels in 26 milk samples taken between 8.1 and 27.5 weeks postpartum averaged 0.35 mEq/L (range 0.19 to 0.48 mEq/L). No difference was found between concentrations in fore- and hindmilk samples.[4]

One woman who was taking 1200 mg of lithium carbonate daily (dosage schedule and product not reported) had a milk lithium concentration of 0.41 mmol/L at 20 hours after her previous dose. This was about the same as her simultaneous blood concentration.[13]

Infant Levels. The serum lithium levels in the breastfed infants of mothers taking lithium have ranged from 10 to 50% of simultaneous maternal serum lithium levels.[6][10][12][14] One infant, who previously had a serum level about 50% of the mother's, became dehydrated and developed a serum level that was double that of the mother's.[14]

Ten exclusively breastfed infants whose mothers were taking an average of 850 mg daily of lithium carbonate had serum levels of 0.16 mEq/L or 24% (range 11 to 56%) of maternal serum levels.[4]

Two breastfed infants (extent not stated) were reported whose mothers were taking lithium carbonate during pregnancy and postpartum. The first mother was taking 1200 mg daily and the infant's serum concentrations were 0.11 mmol/L on day on day 4 and undetectable (<0.1 mmol/L) on days 6 and 10 postpartum. The second mother was taking 900 mg daily and her breastfed infants's serum lithium concentration was undetectable (<0.3 mmol/L) on day 3 of life. Both infants had other serum concentration measurements that were in the therapeutic or toxic ranges, but displayed no symptoms. These samples apparently had been collected in tubes containing lithium heparin.[13]

A woman took lithium carbonate orally 800 mg daily during pregnancy and postpartum while exclusively breastfeeding her infant. The mother had a serum lithium concentration of 0.74 mmol/L at 15 days postpartum. The infant's serum lithium concentration was 0.26 mmol/L at this time. Further serum lithium concentrations in the infant were 0.23 mmol/L at 1 and 2 months of age and 0.17 mmol/L at 6 months of age.[15]

Three mothers took lithium carbonate during pregnancy and breastfeeding. One mother took a dosage of 900 mg daily during 2 pregnancies. Her infants' serum lithium concentrations were 0.08 mEq/L at 31 days and 183 days postpartum in the first pregnancy and 0.11 mEq/L at 43 days of age in the second pregnancy. These values were 11%, 17% and 15% of the mother's simultaneous serum lithium concentrations, respectively. The second mother also took a dosage of 900 mg daily. Her infant's serum lithium concentration was 0.08 mEq/L at 39 days postpartum, or 10% of the mother's simultaneous serum lithium concentration. The third mother took a dosage of 1350 mg daily. Her infant's serum lithium concentration was 0.11 mEq/L at 31 days postpartum, or 11% of the mother's simultaneous serum lithium concentration.[2]

Effects in Breastfed Infants

In older reports, at least 24 infants have been reported to have been breastfed during maternal lithium therapy without any signs of toxicity or developmental problems. All were breastfed from birth and some continued to nurse for up to 6 months of maternal lithium therapy.[4][6][7][8][12][13][15]

A 5-day-old infant developed cyanosis, lethargy, ECG T-wave inversion probably caused by lithium in breastmilk.[10] The mother had been receiving the long-acting diuretic chlorthalidone prior to delivery which probably decreased the infant's lithium elimination and increased the neonate's lithium serum levels. Another case of probable infant lithium intoxication appeared only after the infant had a cold which may have led to dehydration and decreased lithium excretion.[14][16] Two other infants had slight increases in thyrotropin (TSH) levels at 8 and 4 weeks of age, respectively, after lithium exposure that began during pregnancy. Elevated TSH continued until maternal lithium was stopped in one,[4] and normalized by 2 months postpartum in the other, despite continued exclusive breastfeeding.[15]

Three mothers took lithium carbonate during pregnancy and breastfeeding. The first infant was born to a mother who also took bupropion 300 mg and levothyroxine 50 to 75 mcg daily. She breastfed beyond 1 year of age. Her infant did not regain birth weight by 15 days of age, was somewhat hypotonic at 2 months of age, and was treated for gross and fine motor delay for the first year of life. The mother had a second infant on the same drug regimen. She exclusively breastfed her infant who developed normally without hypotonia. A second mother was taking a lithium dosage of 900 mg daily. Her infant gained weight slowly, but weight gain increased with breastfeeding support and she exclusively breastfed her infant for 4 months. A third mother was taking 1350 mg of lithium daily as well as escitalopram 10 mg, levothyroxine 25 mcg and heparin (dosage not stated) daily during pregnancy and breastfeeding. Her infant was normal and was exclusively breastfed until 8 weeks of age when the maternal serum lithium concentration was excessive at 2.0 mEq/L. Breastfeeding was withheld for 2 days and the dosage lowered to 600 mg daily. She then breastfed successfully until 7 months of age.[2]

Effects on Lactation and Breastmilk

Lithium increases serum prolactin.[17][18][19] Galactorrhea was reported in a women taking lithium carbonate for 50 days. Lactation ceased with lithium discontinuation.[19] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

References

1. Grandjean EM, Aubry JM. Lithium: updated human knowledge using an evidence-based approach: part III: clinical safety. CNS Drugs. 2009;23:397-418. PMID: 19453201

2. Bogen DL, Sit D, Genovese A, Wisner KL. Three cases of lithium exposure and exclusive breastfeeding. Arch Womens Ment Health. 2012;15:69-72. PMID: 22277970

3. Ketter TA, Suppes T, Morrell MJ et al. Reproductive health and bipolar disorder. CNS Spectr. 2006;11 (5 Suppl 5):1-16. PMID: 16641845

4. Viguera AC, Newport DJ, Ritchie J et al. Lithium in breast milk and nursing infants: clinical implications. Am J Psychiatry. 2007;164:342-5. PMID: 17267800

5. Schou M, Amdisen A. Lithium and pregnancy--III, lithium ingestion by children breast-fed by women on lithium treatment. Br Med J. 1973;2:138. PMID: 4699592

6. Sykes PA, Quarrie J, Alexander FW. Lithium carbonate and breast-feeding. Br Med J. 1976;2:237. PMID: 1000200

7. Weinstein MR, Goldfield M. Lithium carbonate treatment during pregnancy. Dis Nerv Syst. 1969;30:828-32. PMID: 5369134

8. Wise MG, Javors MA, Funderburg LG et al. Lithium levels in bodily fluids of a nursing mother and infant. Lithium. 1990;1:189-91.

9. Shimizu M, Matsuda H, Sakaue N et al. [A few findings on lithium levels in mother milk -- from one case which fell into a manic state after childbirth]. Seishin Shinkeigaku Zasshi. 1981;83:399-405. PMID: 7330110

10. Tunnessen WW Jr, Hertz CG. Toxic effects of lithium in newborn infants: a commentary. J Pediatr. 1972;81:804-7. PMID: 5074360

11. Fries H. Lithium in pregnancy. Lancet. 1970;295:1233. Letter. PMID: 4192416

12. Moretti ME, Koren G, Verjee Z et al. Monitoring lithium in breast milk: an individualized approach for breast-feeding mothers. Ther Drug Monit. 2003;25:364-6. PMID: 12766565

13. Tanaka T, Moretti ME, Verjee ZH et al. A pitfall of measuring lithium levels in neonates. Ther Drug Monit. 2008;30:752-4. PMID: 19057375

14. Skausig OB , Schou M. [Breast feeding during lithium therapy]. Ugeskr Laeger. 1977;139:400-1. PMID: 841726

15. Marin Gabriel MA, Olza Fernandez I, Donoso E, Gutierrez Cruz N. [Lithium and artificial breastmilk; or is maternal breastfeeding better?]. An Pediatr (Barc). 2011;75:67-8. PMID: 21420368

16. Schou M. Lithium treatment during pregnancy, delivery, and lactation: an update. J Clin Psychiatry. 1990;51:410-3. PMID: 2211538

17. Basturk M, Karaaslan F, Esel E et al. Effects of short and long-term lithium treatment on serum prolactin levels in patients with bipolar affective disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:315-22. PMID: 11294478

18. Cowen PJ, Cohen PR, McCance SL et al. 5-HT neuroendocrine responses during psychotropic drug treatment: an investigation of the effects of lithium. J Neurosci Methods. 1990;34:201-5. PMID: 2259242

19. Ohishi K, Higashimura T. A case of manic state in which lactation occurred after Li2CO3 administration. Folia Psychiatr Neurol Jpn. 1983;37:33-6. PMID: 6411540

Lithium Identification

Substance Name

Lithium

CAS Registry Number

554-13-2

Drug Class

Lithium

Administrative Information

LactMed Record Number

293

Last Revision Date

20140708

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