last updated 3/16/2024
Lamotrigine is another anti-seizure medication psychiatrists have borrowed from the neurologists. We have been using it now for almost 20 years, because several different research studies have shown that in addition to mood stabilizing effects, lamotrigine has clear antidepressant effects as well. It does not have reliable anti-manic effects, so it’s not enough, by itself, for Bipolar I. But for Bipolar II, it can be perfect: 100% symptom control, 0% side effects. (There’s just one big, short-term risk, as you’ll see below: the Rash story)
lamotrigine’s low risks make it a top choice
If I had only one medication for patients with Bipolar II, lamotrigine would be it for sure. Some experts are not so enthusiastic, because research on lamotrigine’s benefits has produced mixed results.
But one thing is clear: lamotrigine has far fewer risks than other medications you might consider instead. True, for the first 6-8 weeks, there’s the risk of a severe allergic reaction; more on that below. But after that, there are no significant risks at routine doses.
So while the evidence for lamotrigine’s benefit is not as good as it is for some other medications you might consider (quetiapine, for example), if it works, it’s a much better longer-term solution than the others.
lamotrigine can make you worse, too (darn)
Lamotrigine’s antidepressant effect could be a bad thing if it can “destabilize” bipolar disorder as typical antidepressants can do. There is little published evidence of such an effect; indeed, in the largest placebo-controlled study so far, no patients had manic symptoms triggered by lamotrigine.Calabrese But I am sure I’ve seen hypomania emerge in people starting lamotrigine.
A colleague who uses it a lot and I were surprised to discover we were both estimating that about 1 person in 20-30 gets worse on lamotrigine, as though they were taking an antidepressant. (There are only a few case reports of this kind of worsening, suggesting our estimate is too high. But those reports tend to be describing mania whereas my colleague and I were counting hypomania and subtle mixed states).
Bottom line: if lamotrigine seems to help at first but then as the dose goes up, you feel over-energized (anxious, agitated), tell your prescriber. They probably don’t know of this effect of lamotrigine but you can discuss a plan for going down a step or two and re-thinking.
The allergic reaction (rash)
The main problem with lamotrigine is not really a side effect but an allergy: lamotrigine can cause a serious skin rash for 1-in-2,000 patients, or even less, according one research study. (On the internet you’ll often see a rate of 1-in-1,000 but that’s oversimplifying.)
Just to make things complicated, there’s a safe rash (“benign”, meaning not dangerous, though bothersome) that happens to about 1 person in 10.
Starting the medication very slowly (basically cutting the usual doses in half; 12.5 mg instead of 25 mg, and so on all the way up) decreases the likelihood of rashes. But it slows the whole process, so sometimes I’d use the standard rate, sometimes half, sometimes somewhere in between, all depending on the patient’s needs for speed versus risk-reduction.
If a rash does develop, it does not necessarily mean lamotrigine must stop. See more on “handling the rash“.
Otherwise I’ve only had to stop the medication in 2 people for ankle swelling, and sometimes for hair loss (yes, it can do that; not very often). 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. (Headache? slow down…)
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. There is a rare chance of a really bad headache, called “aseptic meningitis”. So rare, it took years to figure out that this medicine could cause it (40 reported cases in 15 years).
Headache and nausea
These are common when people are just starting. In almost every case I’ve been able to work around them by lowering the dose a step then going up by smaller steps. Once I had to use the pediatric 5 mg dose to get started.
Bottom line: you don’t need to try to tolerate these symptoms. Tell your prescriber and discuss going down and then up again by smaller steps.
Too high a dose: cognitive slowing
When the dose is too high, lamotrigine can make people think more slowly. This is not a side effect, it’s a dosing error. But it’s definitely a problem worth solving, by lowering the dose a little. Because sometimes the problem is so subtle, people don’t even recognize its happening to them. Yet when the dose goes down, they realize: oh, I was not thinking right.
The most common version of this problem is difficulty finding words. That happens to all of use (especially those of us getting on in years, ahem). But if word-searching seems odd, too frequent, that could be lamotrigine.
This is common at 300 mg per day. At 400 mg per day, nearly everyone gets it. At 200 mg, it’s not so common, but worth keeping an eye out for it. Very often, the full benefit of lamotrigine is still there when the dose is lowered by 50 mg. Once I had to go all the way down to 100 mg daily to help a patient get rid of this problem.
Conclusion
Except for the potential to act too much like an antidepressant, lamotrigine has remarkably few risks. The rash story gets maybe a bit too much attention, though understandably. Manage the dose carefully and lamotrigine should be side-effect free, with no major long-term risks. Very few treatment options are this low in risk.
If it works, great — and it sure seemed to work among my patients, over and over. If not, there are several alternatives.
References
Mockenhaupt M, Messenheimer J, Tennis P, Schlingmann J. Risk of Stevens–Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology. 2005 Apr 12;64(7):1134-8.
Nakamura T, Tomita M, Hirota S, Matsunaga T, Uchimura N. Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders. Journal of Clinical Psychopharmacology. 2022 Jul;42(4):350.