Lamotrigine (Lamictal) has been effectively used for the maintenance treatment of bipolar disorder. Many women suffering from bipolar disorder are of childbearing age; therefore an adequate contraception is a major concern that needs to be addressed in this population.
Special consideration should be taken when patients taking lamotrigine plan to use oral contraceptives (OCs). Studies carried out in both healthy volunteers and patients with epilepsy indicate that OCs may alter the blood levels and efficacy of lamotrigine, decreasing its concentration by about 50 % (range 41%-64%) after just one week of co-administration. In addition, during the week of the inactive hormone preparation (“pill-free” week) of oral contraceptive therapy, blood lamotrigine levels rise and can double by the end of that week.
These studies showed that estrogen increases the clearance of lamotrigine by inducing the liver enzymes involved in its metabolism. More rapid metabolism results in lower, and possibly sub-therapeutic, levels of lamotrigine. Therefore, clinicians should consider increasing the dose of lamotrigine to compensate for the marked reduction in lamotrigine when a woman initiates treatment with an oral contraceptive.
In addition, there is a bidirectional interaction between OCs and lamotrigine, in which lamotrigine causes a small reduction (20%) in the blood concentration of progestin (levonorgestrel). While other anticonvulsants may decrease the efficacy of oral contraceptives, lamotrigine has not been shown to affect the efficacy of oral contraceptives. Nonetheless, women are advised to monitor for any changes in their menstrual cycles, such as breakthrough bleeding.
Women taking lamotrigine are advised to review the different options for contraception with their doctor. For a woman taking a stable dose of lamotrigine who wishes to initiate treatment with an oral contraceptive, the maintenance dose may need to be increased in order to maintain a constant blood level. The manufacturer recommends that the dose of lamotrigine should be increased at the same time the OCs are introduced and the dose escalated as needed based on clinical response. Also, it may also be helpful to measure a lamotrigine blood level prior to initiating treatment with OCs which can serve as a target level as the dose is adjusted. Dose increases of lamotrigine should occur according to the schedule recommended by the manufacturer.
If a woman is already taking an oral contraceptive and initiates treatment with lamotrigine, the dose of lamotrigine should be increased gradually according to the recommended schedule. However, the clinician should be aware that the dose of lamotrigine required for clinical response may be higher than in women who are not taking oral contraceptives. If the woman discontinues treatment with the OC, she may need to lower her dose of lamotrigine, as it will increase once the OC is stopped.
As there is a gradual and transient increase in levels during the pill-free week, patients should contact their doctor if they develop any of the following symptoms suggestive of lamotrigine toxicity: dizziness, lack of coordination and/or blurred or double vision. Although Stevens-Johnsons syndrome has been associated with rapid increases in lamotrigine blood levels, no cases have been reported in women taking oral contraceptives.
Given the complexities of these interactions between lamotrigine and oral contraceptives, some women may elect to avoid OCs altogether. Other hormone-containing contraceptives such as the Ortho-Evra patch, the NuvaRing and Mirena IUD may also affect lamotrigine levels. Thus, barrier methods and non-hormonal IUDs may be more attractive options for women taking lamotrigine.
M. Pia Rogines Velo Sardi, MD, PhD
Ruta Nonacs, MD, PhD
Hadine Joffe, MD, MSc
Christensen J, Petrenaite V, Atterman J, Sidenius P, Ohman I, Tomson T, Sabers A. Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia. 2007 Mar;48(3):484-9.
Sidhu J, Job S, Singh S, Philipson R. The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Br J Clin Pharmacol. 2006 Feb;61(2):191-9..