We get many questions about the interaction between lamotrigine (Lamictal) and oral contraceptives (OCs). While many readers raise concerns that lamotrigine may decrease the effectiveness of oral contraceptives, the primary interaction is actually in the other direction. In other words, oral contraceptives may decrease the effectiveness of lamotrigine.
Studies have shown that estrogens, which are contained in most oral contraceptives, increase 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. In both healthy volunteers and patients with epilepsy, studies have demonstrated 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.
Other studies have suggested that lamotrigine may causes a small reduction (20%) in the blood concentration of progestin (levonorgestrel) contained in OCS. While other anticonvulsants may decrease the effectiveness 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, which may indicate that the levels of hormones have changed.
Based on these findings, we can offer the following guidelines:
If a woman is taking lamotrigine and initiates treatment with an oral contraceptive:
Because estrogen induces the metabolism of lamotrigine, levels of lamotrigine may fall and become subtherapeutic. Thus, many women who initiate treatment with an OC may have to increase their dose of lamotrigine. 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, some may find it 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.
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.
If a woman is 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 in women on OCs than in women who are not taking oral contraceptives.
If a woman is taking an OC and lamotrigine and discontinues the oral contraceptive:
Without the higher estrogen levels from the oral contraceptive, the levels of lamotrigine may increase. The woman may therefore need to lower her dose of lamotrigine. It may be helpful to obtain a lamotrigine level prior to discontinuing the oral contraceptive in order to more precisely adjust the dosage of lamotrigine.
Other Options
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.
Ruta Nonacs, MD PhD
Christensen J, Petrenaite V, Atterman J et al: Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia Mar 1, 2007; 48(3):484-489.
Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia. 2005;46:1414-1417.
Sabers A, Buchholt J, Uldall P et al: Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 2001; 47:151-154.
Sabers A, Ohman I, Christensen J et al: Oral contraceptives reduce lamotrigine plasma levels. Neurology 2003; 61(4):1-4.
Thank you for another clinically relevant and timely article. I would be interested in more detail about the interactions specifically with progesterone-only contraceptive options such as Nexplanon or Mirena (alluded to at the end, but without much specific detail), as well as the Long-Acting Contraceptives in general which are generally more preferred based on greater efficacy.
This is an excellent question. When I wrote this post, I looked for more specific data on the interaction but did not find any useful information. Reassuringly I did not find any reports of contraceptive failure in women taking lamotrigine.