lamotrigine for bipolar disorder

PsychEducation.org (home)

lamotrigine (Lamictal)
(revised 5/2008)

(Skip to the 1-line conclusion)

The Good Side

Lamotrigine is another anti-seizure medication we psychiatrists have borrowed from the neurologists. They have been using it now for about 10 years. Surprisingly, several different research studies have shown that in addition to mood stabilizing effects, lamotrigine has clear antidepressant effects as well.

Obviously it's a good thing if your mood problem is mostly depression and you only have a little evidence of "hypomania" as discussed on this website. For people like this, lamotrigine may be the best option among the mood stabilizers. I won't say too much good stuff about lamotrigine here, though tempted, because if I did, you shouldn't trust it: the manufacturer has been one of the most helpful to me, supporting my efforts to teach about bipolar disorder -- with money, in the form of grants and "honoraria" for giving presentations. The way I use their money, and the reasons why I don't think it's overly influenced me, are described in some detail on my Funding page. But I really like this medication for what it has done for many of my patients, and I'd encourage you to look around at other sites and see what people are saying about lamotrigine. If I had only one medication for patients with bipolar II, this would be it for sure.

[Update 2006: a team of experts seems to think likewise, having placed lamotrigine as "Step One" in the treatment of bipolar depression , in the most recent revision of their practice guidelines. This is the step-by-step guide developed for the entire state of Texas. For more details on these guidelines and the recent change, take this TMAP link.]

However, the antidepressant effect could be a bad thing if it can "destabilize" bipolar disorder like typical antidepressants do. There is little published evidence of this; indeed, in the largest placebo-controlled study so far, no patients had manic symptoms triggered by lamotrigine.^Calabres^e Dr. Calabrese himself speaks very confidently that lamotrigine does not cause manic symptoms. But I am pretty sure I've seen that happen; and there is one case report describing hypomania apparently induced by lamotrigine.^Margolese However, if this does indeed happen, it now appears to be very uncommon, certainly far less than antidepressant-induced hypomania or cycling. [Update 1/2006: Three cases, carefully selected to suggest lamotrigine's potential to bring on manic symptoms, were just published this month.^Raskin The authors comment that a rapid dose increase was used in all three cases and that this might have influenced the apparent association of lamotrigine and the manic symptoms described. If so, we have another reason to go up slowly on the dose. The main reason to do so is described in the next section.]

The Bad Side

The main side effect concern (besides this one, there are amazingly few) for lamotrigine is not really a side effect but an allergy: this medication can cause a serious skin rash.^Calabrese When we first started using it, about 1 person in 10 was getting a rash, which is a high frequency of an allergic reaction to a medication. However, it seems that starting the medication very slowly decreases the likelihood of this rash. I use an extremely slow start , about 1/4 of the originally recommended starting rates. (Several of my colleagues had "evolved" similarly slow rates, we discovered when comparing notes!) Since going this slowly, I've had very few patients develop a rash. See more on "handling the rash", especially if you're a doctor with concerns about using this medication.

However, the rash is nearly the only side effect of concern with this medication. Except for the rash, I've only had to stop the medication in 2 women for ankle swelling. Sometimes it just doesn't work, and sometimes it seems to potentially be making things worse (like an antidepressant might do), but only extremely rarely is a person simply unable to take the medication due to a side effect problem of any kind. That is a remarkable track record compared to many of our other medications (no weight gain problems have been described, or seen by me, for example).

And finally, it definitely works: the antidepressant action seems very beneficial for some patients. Several patients have said "this makes me feel normal" (unfortunately, one of them got the rash shortly thereafter, as this was before we learned to go so slowly. This has led me to go extremely slowly with the dose increases to avoid repeating this experience, as explained in "handling the rash"). Lamotrigine seems to have a different quality as a mood stabilizer than Depakote or Trileptal, which are similar; or even lithium. For more on this medication, see Dr. Ivan’s extensive presentation.^{Goldberg (b)}

Conclusion: lamotrigine seems to be a different kind of mood stabilizer than Depakote or lithium, and has extremely low risk of side effects as long as you don't get the rash -- which is less likely if you go up very slowly on the dose. For a cross check of my information, and a good deal more about the medication, see Dr. Ivan's answers to 24 common questions about lamotrigine.

PS
Skeptics may wish to know that all of the above, except for the warning ("don't trust me here") and the updates, was written before I was recruited by the lamotrigine manufacturer to speak for them; and that their representatives and I had some spirited discussions of whether I would speak according to company guidelines. The end result: I say what I want to say, which usually has more to do with how to diagnose bipolar disorder than what medications to use. [The 2006 update above, on lamotrigine possibly causing manic symptoms, is an example. Now that this medication is going generic (around June 2008) I can really speak out about this medication, because the company is no longer scheduling speaking programs. But I do not feel motivated to go back and change anything I've said previously -- except perhaps to express more enthusiasm for this medication, as reflected in my main Web section on treatment.]

Update 2008: How does this stuff work?
Basically unknown; something about glutamate and/or fast sodium channels seems to be involved. I added this note just so that I could link an interesting article on volunteers who took lamotrigine and experienced a reduction in anxiety while public speaking. The medication decreased the cortisol response to this stress.^Makatsori

A second 2008 article on this subject: might lamotrigine actually do something to Serotonin, perhaps in a fashion similar to typical antidepressants like Paxil/paroxetine? A research paper describing changes in serotonin concentrations similar to those produced by Paxil was just published.^Sagud The authors did a good job tracking other variables that might have influenced their findings. At this stage, their results are just a very preliminary signal that perhaps lamotrigine does indeed do something "serotonergic", possibly similar to what conventional antidepressants do.