SJS is a rare but real risk with lamotrigine, oxcarbazepine and carbamazepine, and some ethnic groups carry a higher, testable risk. Follow the titration protocol exactly, warn patients repeatedly, and tell them to stop the drug and get seen the same day for any new rash.
Who is at risk
Some ethnic groups have a higher risk of SJS with lamotrigine, oxcarbazepine and carbamazepine, and testing is available for the gene that puts them at particularly high risk. For Asian patients starting carbamazepine, the FDA recommends testing for HLA-B*15.
“There are ethnic groups that will have a higher risk of SJS, Steven Johnson syndrome, to lamotrigine, oxcarbazepine, carbamazepine, those kinds of things. Okay. And there is testing available to see if they have the gene that puts them at particularly high risk”
48:28Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 Also said in 1 more episode
“If you have an Asian patient, FDA recommends testing for the HLIB 15 for carbamazepine”
49:07Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 Oxcarbazepine carries the same SJS risk. You cannot tell whether it is higher, because lamotrigine is used so much more and so is tied to many more SJS cases.
“SJS, same SJS risk. You can't tell if it's higher or not because they don't use oxcarbazepine as much as lamotrigine. Lamotrigine is used so much more that is then associated with a lot of SJS cases”
57:58Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026
Prevention
Follow the lamotrigine titration rules exactly. The schedule is slower when you dose alongside an inhibitor of its metabolism, such as Depakote. Follow the protocol and warn, warn, warn.
“You should absolutely follow the rules. Do not titrate. You'll see a slower titration schedule depending on whether you're dosing the same time as an inhibitor of its metabolism, like Depakote, for example, or with other considerations. But follow that protocol and warn, warn, warn”
45:15Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026
When a rash appears
Our instruction to patients: if you get any new rash while we are starting this medication, one you have not had before and that is different, stop the medication and go to the ER.
“We're talking about a rash that is new and that you haven't had before and that's different. If you get any new rash while we're starting this medication, I want you to stop the medication and go to the ER. That's how I do it”
46:07Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 A same-day dermatology appointment works too. A dermatologist will know a lot better than an emergency room doctor whether it is SJS.
“if you can get a same-day appointment of a dermatologist, you can do that too. Because to be frank, they're actually going to know a lot better than any emergency room doctor about whether or not it's SJS”
47:34Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 Never tell a patient the rash is not a big deal. Give the proper response even when the system behind you is not built to respond to it appropriately.
“don't be like, you know, the rash isn't that big a deal. Like, why don't you, like, you have to still give the proper responses, even if the system behind you is not built to appropriately respond to it”
47:13Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026
Talking to patients
Lamotrigine is the most well-tolerated mood stabilizer by a long shot. Because SJS is rare, we phrase the risk to patients as an allergic reaction.
“it is, as you say, it's the most well-tolerated mood stabilizer by a long shot. And frankly, I like to phrase the SJS risk because of its rarity as an allergic reaction”
44:36Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026
It also comes up on
- CarbamazepineIt can cause Stevens-Johnson syndrome and it is a teratogen, so using it in women of reproductive age is a different ballgame. Start thinking of it more like valproate.
- LamotrigineValproic acid jacks up lamotrigine levels, and rising lamotrigine is what we fear because of SJS. Whenever you combine them, halve the lamotrigine. Better still, avoid the combination, which is a huge pain, and review the protocol carefully if you must.
- OxcarbazepineWarn about SJS. You do not need oxcarbazepine levels; some people get them, but they are not very helpful clinically.
- PregnancyCarbamazepine can cause Stevens-Johnson syndrome and is a teratogen, so using it in reproductive-age women is a whole different ballgame. Start thinking of it more like valproate.
- ValproateValproic acid jacks up lamotrigine levels, the dangerous direction because of SJS, so halve the lamotrigine when combining them. Better still, avoid the combination: it is a huge pain, and if you must, review the protocol carefully.
- Drug interactionsValproic acid jacks up lamotrigine levels. That is the dangerous combination because of SJS, so halve the lamotrigine whenever you use them together.
From these episodes
- Mood Stabilizers for Bipolar Disorder: Lithium, Lamotrigine, Depakote & MoreJul 2026 · 8 points
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.