Lamotrigine (Lamictal) Dosing During Pregnancy

Lamotrigine (Lamictal) Dosing During Pregnancy

For many women with bipolar dysfunction, lamotrigine (Lamictal) is an efficient temper stabilizer.  Given its favorable reproductive security profile, lamotrigine (LTG) is an affordable choice for women who require remedy with a temper stabilizer throughout being pregnant.  

When advising women concerning using medicines throughout being pregnant, we sometimes suggest that women stay on the identical dose of remedy that has stored them nicely previous to being pregnant.  Reducing the dosage of remedy could lead to sub-therapeutic ranges, which can in flip enhance the chance of relapse throughout being pregnant regardless of upkeep of the remedy.  

Maintenance of ample dosage throughout being pregnant is particularly vital; there are knowledge to point that ranges of many medicines could lower throughout being pregnant attributable to adjustments in fluid quantity and will increase in hepatic metabolism.  Lamotrigine ranges can decline considerably throughout being pregnant.  Estrogen will increase the clearance of lamotrigine by inducing the liver enzymes concerned in its metabolism. Thus, extra speedy metabolism can lead to decrease, and probably sub-therapeutic, ranges of lamotrigine throughout being pregnant.

As estrogen ranges steadily rise over the course of being pregnant, lamotrigine ranges could drop by as a lot as 50%.  As there’s substantial variability in lamotrigine clearance between people, some women could expertise a big drop in lamotrigine blood ranges throughout being pregnant whereas others could expertise a extra modest decline.  In the setting of falling ranges, some women could expertise medical destabilization. 

A current research signifies that will increase in lamotrigine clearance can start as early as 5 weeks gestational age, usually earlier than women are conscious that they’re pregnant, and clearance continues to extend by way of gestational week 32 (Pennell et al, 2004).

Should the Lamictal Dose Be Adjusted During Pregnancy?

While our group doesn’t sometimes enhance the dose of lamotrigine throughout being pregnant within the absence of medical adjustments.  Some clinicians enhance the dosage of lamotrigine throughout being pregnant to take care of pre-pregnancy blood ranges in sufferers with bipolar dysfunction.  For instance, Clark and colleagues use an strategy modeled after the administration of seizure problems and suggest adjusting lamotrigine dosing throughout being pregnant in line with blood ranges.  

In alignment with the suggestions of lamotrigine dosing in women with epilepsy, Clark recommends that previous to being pregnant, a reference LTG plasma focus needs to be obtained.  During being pregnant, plasma concentrations of LTG needs to be measured each 4 weeks, and the dose needs to be elevated by 20-25% if LTG ranges fall beneath the pre-pregnancy degree.  After supply, the plasma focus of LTG needs to be measured throughout the first or second week, and the dose needs to be decreased by 20-25% and the process repeated till pre-pregnancy ranges are  re-established.

Lamotrigine serum ranges return to pre-pregnancy values inside 3 to 4 weeks after supply. If the dose of lamotrigine was elevated considerably throughout being pregnant, the affected person needs to be monitored for any indicators of toxicity (e.g. nausea, dizziness, imaginative and prescient adjustments, altered psychological standing) through the first few weeks after supply, and the dose ought to steadily be decreased to pre-pregnancy ranges.  

In a response to this text, Sharma and colleagues questioned this strategy, as there isn’t any proof to point that decrease blood ranges of lamotrigine are related to elevated danger for relapse.  Sharma additionally famous that if signs have been to emerge throughout being pregnant, different medicines, such because the atypical antipsychotics, could show to be more practical than lamotrigine for managing sleep disruption, hypomania or mania and may additionally act extra shortly. Higher lamotrigine doses used throughout being pregnant, particularly if not clinically warranted, may additionally enhance danger for neonatal toxicity.  

Making Decisions within the Absence of Clear Guidelines

In sufferers with seizure problems, blood ranges of lamotrigine in a given particular person are strongly correlated with seizure management.  However, in sufferers with bipolar dysfunction, there’s extra seemingly a broader vary of therapeutic blood ranges for lamotrigine. Thus, women could possibly tolerate fluctuations in LTG ranges throughout being pregnant with out vital danger for relapse.  In distinction to temper stabilizers like lithium, the place there’s a outlined therapeutic vary for blood ranges, there isn’t any such guideline for dosing lamotrigine.  

In sufferers who current previous to being pregnant, it might be useful to measure a baseline serum LTG degree to information dosing choices in a while throughout being pregnant if there’s any change in signs; nevertheless, we wouldn’t have clear proof at this level to point that tight management of lamotrigine ranges throughout being pregnant is required or if this strategy decreases the chance of relapse.  Following the affected person’s signs carefully and making remedy changes as wanted permits us to make use of decrease doses of remedy; nevertheless, in sufferers who’re very delicate to adjustments in LTG dosage, nearer monitoring of LTG blood ranges could also be preferable.   

Ruta Nonacs, MD PhD

References:

Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL.  Lamotrigine dosing for pregnant patients with bipolar disorder.  Am J Psychiatry. 2013 Nov 1;170(11):1240-7.

Fotopoulou C, Kretz R, Bauer S, Schefold JC, Schmitz B, Dudenhausen JW, Henrich W.  Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period.  Epilepsy Res. 2009 Jul;85(1):60-4. 

Karanam A, Pennell PB, French JA, Harden CL, Allien S, Lau C, Barnard S, Callisto SP, Birnbaum AK.    Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age.  Ann Neurol. 2018 Oct;84(4):556-563. 

Newport DJ, Stowe ZN, Viguera AC, Calamaras MR, Juric S, Knight B, Pennell PB, Baldessarini RJ.  Lamotrigine in bipolar disorder: efficacy during pregnancy.  Bipolar Disorders 2008;10:432-436.

Pennell PB, Newport DJ, Stowe ZN, Helmers SL, Monbomery JQ and Henry TR.  The impact of pregnancy and childbirth on the metabolism of lamotrigine.  Neurology 2004;62:292-295.

Sabers A.  Algorithm for lamotrigine dose adjustment before, during, and after pregnancy.  Acta Neurol Scand. 2012 Jul;126(1):e1-4. 

Sharma V, Sommerdyk C.  Management points throughout being pregnant in women with bipolar dysfunction.  Am J Psychiatry. 2014 Mar;171(3):370-1.

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