Lithium dosing strategies during pregnancy and the postpartum period

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See editorial, pp. 3–4, this issue.

Declaration of interest

None.

Richard Wesseloo, MD, Department of Psychiatry, Erasmus Medical Centre, 's Gravendijkwal 230, 3000 CA, Rotterdam, The Netherlands. Email: [email protected]

Lithium is currently the most effective mood stabiliser and widely used as a first-line treatment in bipolar spectrum disorder. It has beneficial treatment effects during manic episodes, is associated with a reduction in suicide risk and is highly effective for relapse prevention. ¹ However, lithium needs to be dosed very carefully because of its narrow therapeutic window. In clinical practice, serum measurements provide crucial guidance to avoid both subtherapeutic (<0.5 mmol/L) or toxic (>1.2 mmol/L) blood levels. ^2–5 In addition, it is important to check for renal dysfunction, natrium depletion, dehydration and drug interactions, which can all cause lithium blood level changes. ^5,6 Dosing of lithium is particularly challenging during pregnancy as a result of the normal physiological adaptations of renal function. During pregnancy, increased glomerular filtration rate (GFR) leads to substantial reductions in lithium blood levels and an increased risk of relapse. ⁷ Therefore, clinicians are often inclined to increase patients' lithium dose during pregnancy in an effort to maintain adequate prophylactic blood levels. However, later in pregnancy and during the early postpartum period when GFR returns to preconceptional levels, the increased lithium dose can result in toxic lithium blood levels. ^7,8 Toxic lithium levels are concerning not only for the mother, but particularly for the infant in whom the adverse neonatal effects of lithium, such as hypoglycaemia, cardiac arrhythmia, thyroid dysfunction and neonatal lithium toxicity are dose related. ^9,10 Moreover, during the early postpartum period, lithium dosing is challenging because of the very high risk for postpartum relapse (37%, 95% CI 29–45) in women with bipolar disorder. ¹¹ Therefore, increased therapeutic lithium blood levels are warranted during this high-risk period. Current clinical guidelines provide limited details regarding the optimal approach for monitoring lithium blood levels during pregnancy and the postpartum period. Therefore, in an effort to define an evidence-based strategy for dosing lithium during pregnancy, we investigated a cohort of women (n = 85 representing n = 113 pregnancies) for whom lithium blood levels were measured (n = 1101) longitudinally during pregnancy and the postpartum period.

Method

Participants

All women referred...