For a lot of ladies with bipolar dysfunction, lamotrigine (Lamictal) is an efficient temper stabilizer. Given its favorable reproductive security profile, lamotrigine (LTG) is an inexpensive choice for girls who require therapy with a temper stabilizer throughout being pregnant.
When advising ladies concerning the usage of medicines throughout being pregnant, we sometimes advocate that ladies stay on the identical dose of remedy that has stored them properly previous to being pregnant. Lowering the dosage of remedy might lead to sub-therapeutic ranges, which can in flip enhance the chance of relapse throughout being pregnant regardless of upkeep of the remedy.
Upkeep of sufficient dosage throughout being pregnant is particularly necessary; there are knowledge to point that ranges of many medicines might lower throughout being pregnant on account of 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 step by step rise over the course of being pregnant, lamotrigine ranges might drop by as a lot as 50%. As there may be substantial variability in lamotrigine clearance between people, some ladies might expertise a big drop in lamotrigine blood ranges throughout being pregnant whereas others might expertise a extra modest decline. Within the setting of falling ranges, some ladies might expertise medical destabilization.
A latest examine signifies that will increase in lamotrigine clearance can start as early as 5 weeks gestational age, typically earlier than ladies are conscious that they’re pregnant, and clearance continues to extend by way of gestational week 32 (Pennell et al, 2004).
Ought to the Dose Be Adjusted Throughout Being pregnant?
Whereas 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 keep up pre-pregnancy blood ranges in sufferers with bipolar dysfunction. For instance, Clark and colleagues use an method modeled after the administration of seizure problems and advocate adjusting lamotrigine dosing throughout being pregnant in line with blood ranges.
In alignment with the suggestions of lamotrigine dosing in ladies with epilepsy, Clark recommends that previous to being pregnant, a reference LTG plasma focus must be obtained. Throughout being pregnant, plasma concentrations of LTG must be measured each 4 weeks, and the dose must be elevated by 20-25% if LTG ranges fall beneath the pre-pregnancy degree. After supply, the plasma focus of LTG must be measured throughout the first or second week, and the dose must be diminished 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 must be monitored for any indicators of toxicity (e.g. nausea, dizziness, imaginative and prescient adjustments, altered psychological standing) throughout the first few weeks after supply, and the dose ought to step by step be decreased to pre-pregnancy ranges.
In a response to this text, Sharma and colleagues questioned this method, as there is no such thing as a proof to point that decrease blood ranges of lamotrigine are related to elevated danger for relapse. Sharma additionally famous that if signs had been to emerge throughout being pregnant, different medicines, such because the atypical antipsychotics, might show to be more practical than lamotrigine for managing sleep disruption, hypomania or mania and can also act extra shortly. Greater lamotrigine doses used throughout being pregnant, particularly if not clinically warranted, can also enhance danger for neonatal toxicity.
Making Selections within the Absence of Clear Tips
In sufferers with seizure problems, blood ranges of lamotrigine in a given particular person are strongly correlated with seizure management. Nevertheless, in sufferers with bipolar dysfunction, there may be extra probably a broader vary of therapeutic blood ranges for lamotrigine. Thus, ladies might be able to tolerate fluctuations in LTG ranges throughout being pregnant with out important danger for relapse. In distinction to temper stabilizers like lithium, the place there’s a outlined therapeutic vary for blood ranges, there is no such thing as a such guideline for dosing lamotrigine.
In sufferers who current previous to being pregnant, it could be useful to measure a baseline serum LTG degree to information dosing selections in a while throughout being pregnant if there may be any change in signs; nevertheless, we don’t have clear proof at this level to point that tight management of lamotrigine ranges throughout being pregnant is required or if this method 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 sufferers with bipolar dysfunction. 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 adjustments in lamotrigine-concentration in ladies with epilepsy throughout being pregnant, lactation and the neonatal interval. 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 will increase 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 dysfunction: efficacy throughout being pregnant. Bipolar Issues 2008;10:432-436.
Pennell PB, Newport DJ, Stowe ZN, Helmers SL, Monbomery JQ and Henry TR. The influence of being pregnant and childbirth on the metabolism of lamotrigine. Neurology 2004;62:292-295.
Sabers A. Algorithm for lamotrigine dose adjustment earlier than, throughout, and after being pregnant. Acta Neurol Scand. 2012 Jul;126(1):e1-4.
Sharma V, Sommerdyk C. Administration points throughout being pregnant in ladies with bipolar dysfunction. Am J Psychiatry. 2014 Mar;171(3):370-1.
