Lamotrigine and Steven Johnsons syndrome

[the5thelement]

Just saw this article on Daily mail: Utah woman in ICU 3 weeks after starting Lamictal.
The article states it was used as a "anxiety medication". I have started numerous patients
on Lamotrigine but always dread of the remote possibility of something like this happening
to a poor patient. Its my understanding that if your gradually start it, the risk of SJS is minimized (but never zero).
Simply horrific .....

---

Members don't see this ad.

 

[Mad Jack]

Just saw this article on Daily mail: Utah woman in ICU 3 weeks after starting Lamictal.
The article states it was used as a "anxiety medication". I have started numerous patients
on Lamotrigine but always dread of the remote possibility of something like this happening
to a poor patient. Its my understanding that if your gradually start it, the risk of SJS is minimized (but never zero).
Simply horrific .....

Statistically you're looking at 1 in 2500 patients developing SJS or TEN. Over the course of a career, that makes it more likely than not you'll encounter a case if you prescribe it with any frequency. I just titrate slowly, educate, document extensively, and ensure I'm practicing within FDA-approved parameters then hope for the best

 

[FlowRate]

Statistically you're looking at 1 in 2500 patients developing SJS or TEN. Over the course of a career, that makes it more likely than not you'll encounter a case of you prescribe it with any frequency. I just titrate slowly, educate, document extensively, and ensure I'm practicing within FDA-approved parameters then hope for the best

Depending what articles you review and how recent they are, some even estimate lower risk with good adherence to modern slow titration standards IIRC.

I agree it's something important to review but also extremely unlikely to happen.

 

[Merovinge]

If it's actually treating bipolar depression, the risk of SJS when titrated appropriately is dwarfed by the risk of depressive episodes/other medication that treat bipolar depression. Similar if it is effective in TRD. If it ends up providing actual functional improvement in PD/anxiety cases (of which I think it would be rare but possible to do so) then also as above. If it's just Lamictal because I have no idea what to do for the patient then absolutely I do think this concern should ring in the back of one's head before prescribing.

 

[Mad Jack]

If it's actually treating bipolar depression, the risk of SJS when titrated appropriately is dwarfed by the risk of depressive episodes/other medication that treat bipolar depression. Similar if it is effective in TRD. If it ends up providing actual functional improvement in PD/anxiety cases (of which I think it would be rare but possible to do so) then also as above. If it's just Lamictal because I have no idea what to do for the patient then absolutely I do think this concern should ring in the back of one's head before prescribing.

100% agree. It has its place where the risks are far lower than the risks of the alternatives and that's why it's a not infrequent tool in my arsenal

 

[comp1]

Lamotrigine is demonstrably and significantly safer than most alternative medications for bipolar disorder. That said...it's a heck of a lot harder to sue a doctor for the diabetes and high cholesterol you developed due to using an atypical. A lay jury will definitely buy into the argument that it was ultimately the patient's own behavior that lead to metabolic syndrome and they wouldn't be 100% wrong. But all you need to win a SJS suit is photos. It's kind of an indictment of our legal system... Personally, I don't have time for the taper, so I don't use it much. I have read that valproate also has a significant SJS risk, however, and I do use that often.

 

[Celexa]

I love lamotrigine for bipolar 2. Well tolerated and fewer side effects than SGAs.

This is probably a good time to remind that although the focus on the risk of SJS is on the rash, SJS is preceded by a generalized prodrome that usually includes fever and malaise, and it is important to warn patients about this and to stop the med and call you if these symptoms appear in the first weeks/months of taking the med, not just for a rash.

The risk of SJS falls precipitously after the first few months to near irrelevance. The time line described in this article is exactly the most likely way this horrific side effect is most likely happen, although it lacks all information that would indicate if the med was prescribed appropriately. I wouldn't prescribe lamotrigine for an anxiety disorder per se but there are plenty of patients whose chief complaint is 'anxiety' who need their underlying mood disorder addressed first and there's no dosing info in the article to judge how fast she was uptitrated. When I do start Lamictal I am very strict about the slow titration schedule but I have sometimes seen other people prescribe faster.... Definitely not an area I see any benefit to coloring outside the lines. You'd have essentially no defense if the person got SJS if you disregarded typical practice. If the person needs an aggressive medication intervention and symptoms are too severe for them to wait out the titration, you should be prescribing something else.

 

[comp1]

Yes, even a patient SHOULD be able to pretty easily recognize SJS before it gets to the point where you get the photos the jury sees, but I'm sure there are outliers.

 

[Old&InTheWay]

I saw a horrendous case of SJS in a 19-year-old patient a few years ago. She had taken 25 mg daily for two weeks, then developed a rash when she increased to 50 mg that progressed despite stopping the medication. So, even following best practices, it can still happen and stoping the medication doesn't necessarily avoid a severe case.

That said, if I had to personally take a medication for bipolar disorder, I'd still want to try lamotrigine first.

 

[Merovinge]

I love lamotrigine for bipolar 2. Well tolerated and fewer side effects than SGAs.

This is probably a good time to remind that although the focus on the risk of SJS is on the rash, SJS is preceded by a generalized prodrome that usually includes fever and malaise, and it is important to warn patients about this and to stop the med and call you if these symptoms appear in the first weeks/months of taking the med, not just for a rash.

The risk of SJS falls precipitously after the first few months to near irrelevance. The time line described in this article is exactly the most likely way this horrific side effect is most likely happen, although it lacks all information that would indicate if the med was prescribed appropriately. I wouldn't prescribe lamotrigine for an anxiety disorder per se but there are plenty of patients whose chief complaint is 'anxiety' who need their underlying mood disorder addressed first and there's no dosing info in the article to judge how fast she was uptitrated. When I do start Lamictal I am very strict about the slow titration schedule but I have sometimes seen other people prescribe faster.... Definitely not an area I see any benefit to coloring outside the lines. You'd have essentially no defense if the person got SJS if you disregarded typical practice. If the person needs an aggressive medication intervention and symptoms are too severe for them to wait out the titration, you should be prescribing something else.

Which is absolutely a terrible idea. The data is incontrovertible that old/fast titration schedules have a dramatic increase in SJS/TEN incidence. I would almost never testify against another physician but if someone came knocking for a doctor who intentionally put someone on Lamictal at a 100-200mg in a the span of a week or two you can sign me right up.

 

[milesed]

There is a local pcp who gives it to any kid with ODD and his practices seem to have spread to others. The rates I see of SJS seem WAY higher than 1/2500- more like 1/100 from what I see on transfer of his patients to me.

I do like it for adult bipolar patients who are depressed.

 

[ObsequiousAplomb]

There is a local pcp who gives it to any kid with ODD and his practices seem to have spread to others. The rates I see of SJS seem WAY higher than 1/2500- more like 1/100 from what I see on transfer of his patients to me.

I do like it for adult bipolar patients who are depressed.

1 / 100 ? Geeze, how many hundreds do you need to see to say that? And why are you seeing so many hundreds of patients from one person?

 

[Celexa]

There is a local pcp who gives it to any kid with ODD and his practices seem to have spread to others. The rates I see of SJS seem WAY higher than 1/2500- more like 1/100 from what I see on transfer of his patients to me.

I do like it for adult bipolar patients who are depressed.

1/100 with any rash, or 1/100 with believable report of rash + systemic symptoms? Either way that's disturbing.

 

[comp1]

Benign rash is extremely common, I think greater than 10%?

 

[forchinet121]

There is a local pcp who gives it to any kid with ODD and his practices seem to have spread to others. The rates I see of SJS seem WAY higher than 1/2500- more like 1/100 from what I see on transfer of his patients to me.

I do like it for adult bipolar patients who are depressed.

I don’t want to be rude but we have published data on this its 1/2500 not 1/100

 

[calvnandhobbs68]

There is a local pcp who gives it to any kid with ODD and his practices seem to have spread to others. The rates I see of SJS seem WAY higher than 1/2500- more like 1/100 from what I see on transfer of his patients to me.

I do like it for adult bipolar patients who are depressed.

I'm feeling from this post like you don't know what SJS is....

 

[Stagg737]

This is probably a good time to remind that although the focus on the risk of SJS is on the rash, SJS is preceded by a generalized prodrome that usually includes fever and malaise, and it is important to warn patients about this and to stop the med and call you if these symptoms appear in the first weeks/months of taking the med, not just for a rash.

Benign rash is extremely common, I think greater than 10%?

This 100%. I see a lot of patients who developed a rash while on it with no other symptoms and when talks about re-trial occur everyone flips out. If they have/had a rash I ask about other symptoms as well as the actual nature of the rash. While SJS rash can vary, it's got a typical pattern and like mentioned is part of a group of symptoms. Simple rash with no other symptoms is almost certainly not SJS.

Even so, SJS/TEN is scary enough that unless I'm very confident in the patient's insight into their body/symptoms I tell them to d/c lamotrigine if they experience rash and go to the ER/urgent care if the rash continues to worsen the following day. I've seen 3 cases where I'm certain the patient was developing SJS and in all of them progression of the rash stopped when the med was stopped, though symptoms did take up to a week to resolve.

Which is absolutely a terrible idea. The data is incontrovertible that old/fast titration schedules have a dramatic increase in SJS/TEN incidence. I would almost never testify against another physician but if someone came knocking for a doctor who intentionally put someone on Lamictal at a 100-200mg in a the span of a week or two you can sign me right up.

I'm also pretty strict about the 2 week rule and pretty much every psychiatrist I know is as well. I've met plenty of neurologists who have no problems titrating up much quicker though, not sure if they can justify it by arguing benefit for seizures outweigh risks or not.

 

[doctalaughs]

Derm here.

Have probably seen and consulted on 50-100 cases of SJS/TEN (used to work at an academic center with a burn unit long time ago).

Lots from lamictal but probably more from Bactrim since it’s so commonly given. Lots from tegretol, allopurionol, smattering from other antibiotics etc.

I’m sure prescribing docs get sued - but I don’t see how they could win if the risk was discussed and clearly documented and it was stopped when recognized. It’s a rare but known risk of these meds. At least most counsel for lamictal — but most don’t for bactrim.

I know there’s literature on dose dependent triggers but don’t think it’s that good. It just happens (some literature about HLA type predisposition) and sucks when it does. It’s also usually not very subtle and there’s so many other rashes that aren’t SJS/TEN (but happened to occur close to med start) that I get a ton of consults where good meds were stopped for no reason. Good rule of thumb is if the skin doesn’t hurt (ie itches) and there is no mucosal involvement it’s not that, even early on.

Also I would say survivable “mild” SJS/TEN tends to happen more than the horrible cases of 50-100% bsa.