Does lamotrigine decrease the effectiveness of oral contraceptives?

Question from a Member:

I have many patients who refuse to take lamotrigine after their pharmacist (or the Internet) tells them that it will reduce the effectiveness of hormonal contraceptives. Do you know of any research on the rate of birth control failure for women taking lamotrigine?

On another page on this website, we have discussed the effects of oral contraceptives on lamotrigine levels and recommended action items in this regard. But, we continue to repeatedly get the question that our Member asks above. That is, what about the opposite—does lamotrigine affect the effectiveness of oral contraceptives? From emails I get from our Members, it seems that this is widely believed to be the case. The supposition that lamotrigine may reduce the effectiveness of oral contraceptives seems to come from pharmacists and from some websites (example). So, let us look closely at what is known about this.

Findings of a key study

The most commonly used oral contraceptives contain a combination of an estrogen and a progestin. A key study regarding the effects of lamotrigine on combination oral contraceptives that is frequently quoted was a systematic study of a small number of healthy women on combination oral contraceptives who were then given lamotrigine (Sidhu et al., 2006). Here’s a summary of the main findings of this study:

1. Lamotrigine did not affect the serum levels of estrogen

2. But, lamotrigine did reduce the exposure to the progestin (levonorgestrel) by about 20%.

3. Also, lamotrigine was associated with large increases in serum FSH and LH levels, which may indicate loss of the suppression of the hypothalamic-pituitary-ovarian axis.

4. But, importantly, none of the women had an increase in serum progesterone to a level that would indicate ovulation.

5. About a third of these women reported vaginal bleeding between the menstrual periods

The Prescribing Information for lamotrigine summarizes the findings discussed above (Sidhu et al., 2006) and concludes:

“The clinical significance of the observed hormonal changes on ovulatory activity is unknown. However, the possibility of decreased contraceptive efficacy in some patients cannot be excluded. Therefore, patients should be instructed to promptly report changes in their menstrual pattern (e.g., break-through bleeding).”

Any reports of contraceptive failure?

It is reassuring that though lamotrigine has been around for many years, in a PubMed search on July 16, 2020, I could not find a single published case of contraceptive failure related to lamotrigine use.

Drug interaction websites

Epocrates online also does NOT say that lamotrigine may decrease the effectiveness of oral contraceptives.

A second opinion

The authoritative website of the MGH Center for Women’s Mental Health states: “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”. This is restated on the same website on another webpage as well.

Optional to read: In contrast to the above, a small controlled study did not find lamotrigine to have any effect on progestins in women taking combination oral contraceptives (Rauchenzauner et al., 2020).

Clinical Recommendations

As of July 2020, it is not recommended that lamotrigine be avoided or stopped in a woman for whom it is otherwise indicated just because she is on a combination oral contraceptive.

We can tell patients that:

1. Lamotrigine has not been shown to affect the efficacy of oral contraceptives.

2. No cases of lamotrigine-induced contraceptive failure have been published.

3. But, the patient should monitor herself for any changes in their menstrual cycles, such as breakthrough bleeding, and let us and her gynecologist know right away if any such changes occur.

Simple and Practical Medical Education thanks Vivien K. Burt, MD, PhD (bio) for kindly reviewing and approving this article (in July 2020).

Dr. Burt is Professor Emeritus of Psychiatry at the Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, and the Founder and Co-Director, The Women’s Life Center Resnick UCLA Neuropsychiatric Hospital, Los Angeles, California, USA.

Oral contraceptives and lamotrigine

Psychotropic drugs that can lead to unwanted pregnancy!

Top 5 prescribed oral contraceptives (External link)

List of brand names of oral contraceptives (External link)

References

Rauchenzauner M, Deichmann S, Pittschieler S, Bergmann M, Prieschl M, Unterberger I, Rösing B, Seger C, Moser C, Wildt L, Luef G. Bidirectional interaction between oral contraception and lamotrigine in women with epilepsy – Role of progestins. Seizure. 2020 Jan;74:89-92. doi: 10.1016/j.seizure.2019.11.011. Epub 2019 Nov 25. PMID: 31869755.

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. doi: 10.1111/j.1365-2125.2005.02539.x. PMID: 16433873;
PMCID: PMC1885007.

References not used on this page

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Burakgazi E, Harden C, Kelly JJ. Contraception for women with epilepsy. Rev Neurol Dis. 2009 Spring;6(2):E62-7. PMID: 19587632.

Herzog AG, Blum AS, Farina EL, Maestri XE, Newman J, Garcia E, Krishnamurthy KB, Hoch DB, Replansky S, Fowler KM, Smithson SD, Dworetzky BA, Bromfield EB. Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use. Neurology. 2009 Mar 10;72(10):911-4. doi: 10.1212/01.wnl.0000344167.78102.f0. PMID: 19273825.

Sabers A. Pharmacokinetic interactions between contraceptives and antiepileptic drugs. Seizure. 2008 Mar;17(2):141-4. doi: 10.1016/j.seizure.2007.11.012. PMID: 18206393.

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Contin M, Albani F, Ambrosetto G, Avoni P, Bisulli F, Riva R, Tinuper P, Baruzzi A. Variation in lamotrigine plasma concentrations with hormonal contraceptive monthly cycles in patients with epilepsy. Epilepsia. 2006
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Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia. 2005 Sep;46(9):1414-7. doi: 10.1111/j.1528-1167.2005.10105.x. PMID: 16146436.

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