Q:  Any Link Between Lamotrigine & Cleft Lip or Palate?

Dr. Phelps,
I have read on your site here that there has been no significant conclusion as to whether or not the medication lamictal causes serious deformities or retardation in the fetus when one is pregnant. However, it is mentioned (not sure if on your site, I've read so many) that there is a strong possibility of cleft lip or cleft palate with regard to this medication.

Also, just curious when I come off of the lamictal (if my doc agrees to it) before or during pregnancy how long does it stay in your system (a concern of potential harm to fetus) so how long should I be off of it before I do get pregnant?

I thank you for your advice in advance.

Best,
Gina   


Dear Gina --

You are right. There is still no significant conclusion whether lamotrigine (Lamictal) causes any birth defects at all. And you are right, there has been concern raised that there could be a link with causing cleft lip or cleft palate. However, you should downgrade that link to "under consideration", not "strong possibility" for now. We just need more women in the pregnancy registry the manufacturer is maintaining, and that will happen, with time.

If you and your doctor decide to taper off Lamictal before you get pregnant, how long do you need to be off of it in order to remove any potential effects on the fetus? The simple answer is "be off the lamotrigine for seven days before you conceive". But if you are a curious person, as might be the case given that you're asking this question here, you might want to know where that number comes from. And you might want to know how much confidence we should have and that number. So here goes. Brace yourself. Don't forget the simple answer.

Unfortunately, because we really don't know how Lamictal might cause cleft palate, for example, -- if it does -- we don't know whether this is a function of actually having the medication in your bloodstream at the time, or if there might be some lingering effect remaining in mother's body that could somehow be transmitted to the developing fetus later. I should emphasize that this latter possibility, the lingering effect, is merely a theoretical possibility. I've never seen any evidence that this could be so, i.e. some sort of lingering molecule that would be in a position to be transmitted to the fetus. We just have to think through every possibility to properly answer your question.

By far the most likely timing you would need to consider is simply how long does it take for the medication to be removed from your bloodstream. At least that much we know. Or at least we know quite a bit: I just went to look up the "half-life" of lamotrigine. This is the amount of time it takes for the amount in your bloodstream to go down by half. One website says 24-34 hours, which is a pretty broad range. Another website says that the half-life is highly variable, although 24-34 hours is pretty variable, maybe that is what they mean. In any case, it doesn't make too much difference: because medications are removed more quickly when their concentration is high, and more slowly one that is low, the removal rate decreases as the amount and your bloodstream decreases. In other words, we see "exponential decay": fast at the beginning for a steep slope downward initially, then slow at the end with a long flat tail. 

We use a simple rule of thumb to estimate when that tail is getting very close to zero: five half-lives. So for lamotrigine, five x 34 hours would give you an estimate at the longer end. That's 170 hours, about seven days.

Therefore if you presume that there is risk to a developing fetus; and that the risk is associated with having a medication in your bloodstream; then on the basis of those presumptions you would want to taper off lamotrigine and be completely off for at least seven days before conception. I suppose we could wonder about some effect on your egg, prior to conception, but then of course we have to wonder how long before ovulation the egg could be influenced by lamotrigine. Those eggs are sitting there for a long time. So the influence, were we to consider this possibility, could last a long while. Again, may I emphasize that this is just a theoretical consideration. Again, I have seen no evidence that would suggest we need to think like this, except on the basis of general principles.

Indeed, probably the most important thing to remember in this entire consideration is that the rate of birth defects such as cleft lip or palate is so low that we are only just now beginning to be able to detect it, if it is real.

I hope that all this detail is what you are looking for. It's the kind of information I would want if I was looking at the question you raise here. If I have made things too complicated, I apologize.   Good luck with your decision making and your pregnancy --

Dr. Phelps