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
After reading the above, being that Lamictal can decrease progesterone by 20%, what about a woman on depo-provera who wants to use Lamictal? Can the depo injection being given more often mitigate the effects?
Thanks.
Very helpful information, clear and consise, addressing a common problem when treating female patients with Lamictal. Thanks!
Hi – I am wondering if there are any more recent studies looking at the interaction between lamotrigine and estrogen-containing birth control pills (looks like the references are from 2003-2007)? Also, is there an interaction between lamotrigine and endogenous estrogens during the normal monthly cycle of a woman? This is something that I have seen mixed information within the literature and wondered if you knew of any good articles that speak to this.
Great questions. I did not find any articles more recent than the ones posted.
This article indicates that LTG levels do not fluctuate significantly across the menstrual cycle. Perhaps this is because the hormone levels change more rapidly or are lover than what you would see duirng pregnancy or with use of an oral contraceptive. While this is waht the medical literature reports, if I have a woman on lamotrigine with premenstrual worsening of mood, my first inclination would probably be to increase her lamotrigine level.
What would be the reccomended approach for a client that takes Lamotrigine with an OCP and during the pill free week develops toxicity symptoms? But she wants to continue to remain on an OCP for management of other menstrual cycle related irregularities? Should she lower the dose of Lamotrigine during that pill free week? Switch to another OCP? Switch from lamotrigine to another agent?
Wow. I have never seen anybody with toxicity symptoms but it certainly seems plausible given that levels may rise by as much as 50%. So I can’t say that these recommendations are based on my personal experience, but I have some ideas:
1. If she has been doing well on Lamictal, I probably would not change it. Other mood stabilizers have more side effects. (I was assuming that she has bipolar disorder vs. epilepsy.)
2. You could use OCPs continuously and thus expose her to the placebo week much less often.
3. You could try lowering the dose whenever she is during her placebo week. I would not feel so comfortable doing this if this takes place every month; if you undershoot, it may make her more vulnerable to relapse. You could measure Lamictal levels toward the end of the placebo week and immediately before the placebo week to get a sense of how much levels vary. Estrogen decreases levels up to 50%, but I am not sure how long it takes the liver enzymes to up and down regulate, so decreasing the dose by 50% might be too aggressive.
4. With regard to switching contraceptives, you will run into this problems with all forms of OCP. You could consider transdermal – less impact on liver metabolism. Would not recommend progestin only preparation because they sometimes have a negative impact on mood. Mirena IUD? Some people experience mood symptoms with Mirena, but probably less of a risk.
Keep us posted on what works.