Lithium during pregnancy

In considering whether to maintain patients on lithium during pregnancy, the clinician must take into account the risks of an exacerbation of bipolar disorder to both mother and fetus. Although it would be ideal to avoid lithium therapy, at least during the first trimester, when critical organogenesis is occurring, this may not be possible. 

There is no evidence that children exposed to lithium during pregnancy who are born without malformations develop other than normally. 

Yonkers KA, Little BB, March D. Lithium during pregnancy. Drug effects and their therapeutic implications. CNS Drugs 1998 9 261-9. 

Evidence of increase in cardiac anomalies (especially Ebstein s anomaly) in infants whose mothers took lithium during pregnancy... 

Electroconvulsive therapy (ECT) is used for severe mania or depression during pregnancy and for mixed episodes prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. 

When lithium is to be used during pregnancy, it should be used at the lowest effective dose in order to avoid floppy infant syndrome, hypothyroidism, and nontoxic goiter in the infant. 

Lithium clearance increases by 50% to 100% during pregnancy. Serum levels should be monitored monthly during pregnancy and weekly the week before delivery. At delivery, a dose reduction to prepregnancy doses and adequate hydration are recommended. 

Dunner DL, Eieve RR Clinical factors in lithium carbonate prophylaxis failure. Arch Gen Psychiatry 30 229-233, 1974 Edmonds LD, Oakley GP Ebstein s anomaly and maternal lithium exposure during pregnancy. Teratology 41 551-552, 1990 Emrich HM Studies with oxcarbazepine (Trileptal) in acute mania. Int Clin Psychopharmacol 5 83-88, 1990... 

The possibility of lithium exerting other effects" during pregnancy... 

During pregnancy, serum lithium levels need to be carefully monitored. The 50% to 100% increase in glomerular filtration rate (GFR) that normally occurs in the third trimester will proportionally lower lithium levels due to its increased clearance. Thus, dosage may need to be increased to maintain a therapeutic range ( 341). Because the GFR and lithium clearance quickly return to normal after delivery, it may be wise to stop the drug shortly before delivery and restart a few days after delivery at a lower dose. In summary ... 

The changing physiology during pregnancy can alter lithium levels. 

Schou M. Lithium treatment during pregnancy, delivery, and lactation an update. J Clin Psychiatry 1990 51 410-412. 

There is no final consensus on whether normal use of lithium, without any episode of toxicity (the vast majority of patients), may result in permanent renal impairment. Polyuria occurs in 20-40% and is due to inhibition of antidiuretic hormone (ADH) by lithium. It usually resolves on cessation of lithium as do any effects on glomerular function. Interference with thyroid function is due to inhibition of the action of thyroid stimulating hormone (TSH) and is easily managed by administration of thyroxine. Lithium is contraindicated during pregnancy (major vessel anomalies in fetus) and breastfeeding. 

Iqbal MM, Sohhan T, Mahmud SZ The effects of lithium, valproic acid, and carbamazepine during pregnancy and lactation. J Toxicol Clin Toxicol 2001 39 381. [PMID 11527233]... 

The cardiovascular teratogenicity of lithium has been summarized in a review of managing bipolar disorder during pregnancy and postpartum (473). While the risk of Ebstein s anomaly is increased, likely 10-20 times more than in the general population, the absolute risk (0.05-0.10%) is small. Fetal ultrasonography was advised at 18-20 weeks of gestation in cases of first trimester lithium exposure (488). 

A 36-year-old woman with bipolar disorder who had taken lithium for 17 years continued to take it and other medications during pregnancy (493). At 35 weeks she developed signs of lithium toxicity, with nausea, diarrhea, and a concentration of 1.25 mmol/1. She delivered a lethargic infant with poor muscle tone, who showed signs of respiratory distress and hypopnea. 

In 20 infants exposed to lithium during labor and delivery, there were higher rates of perinatal complications (65%) and special care nursery admissions (45%) than in nonexposed infants, although most complications were transient (494). An infant who died shortly after birth had oromandibular-limb hypogenesis spectrum which was speculatively attributed to lithium that the mother had taken during most of her pregnancy (495). 

Atypical antipsychotics may be preferable to lithium or anticonvulsants such as carbamazepine if treatment of bipolar disorder is required during pregnancy... 

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