Lamotrigine titration

[Kuvan]

I was wondering if anyone has seen LTG being titrated every 2 or 3 days in inpatient? I know the guidelines say q 2 weeks. I keep seeing q 2 to 3 days. Today doc asked if it was ok to increase from 25 mg to 50 mg on the 4th day since the pt was on it before and had no problem with it. But the guidelines say after stopping for 5 days, restart with the initial titration schedule. Suggestions?

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[Jules A]

I was wondering if anyone has seen LTG being titrated every 2 or 3 days in inpatient? I know the guidelines say q 2 weeks. I keep seeing q 2 to 3 days. Today doc asked if it was ok to increase from 25 mg to 50 mg on the 4th day since the pt was on it before and had no problem with it. But the guidelines say after stopping for 5 days, restart with the initial titration schedule. Suggestions?

I would consider asking on the neurology forum also as that is likely where you will see more latitude with regard to prescribing seizure meds. I have seen it increased aggressively inpatient psych but don't do it myself out of concern of an ADR after discharge. It is possible I'm extra conservative with regard to this med that, although rare, can have a significant ADR. Obviously I don't want to cause harm nor do I want to to explain this deviation, and why I didn't select a more efficacious medication if quick titration was so crucial, after the fact.

 

[Mad Jack]

2-3 days seems quite cavalier...

 

[hallowmann]

2-3 days seems quite cavalier...

I've seen 5-7 days and people tolerate that OK, but most of the time that titration happens outpatient exactly because of how long it takes.

 

[Bartelby]

Most of the time increasing aggressively would go fine, but when it doesn't you will be out on your own defending nonstandard practice. I wouldn't advise it.

 

[shahseh22]

I hate prescribing Lamictal for this very reason and I almost never start anyone on it.

 

[Mad Jack]

I've seen 5-7 days and people tolerate that OK, but most of the time that titration happens outpatient exactly because of how long it takes.

Usually I see 7 days per increase until they hit 100 mg

 

[Crayola227]

I hate prescribing Lamictal for this very reason and I almost never start anyone on it.

Too bad. I know quite a few patients that like it quite a bit, especially compared to the SE profile of a lot of what's out there. It's really not a bad drug or difficult to prescribe if one follows reasonable guidelines.

 

[Armadillos]

Read this editorial and then decide if it’s worth it.

Treating a Patient With a Nightmarish Condition (Published 2019)

She had lost all of her skin and I feared I had helped make her last weeks an unrelenting horror show, until our chance reunion.

www.nytimes.com

 

[beautifulrobot]

I'm surprised a pharmacist would let that order go through. Their license is on the line as well. Titrating lamotrigine quicker than standard practice/what's recommended in the prescribing information/drug labeling is a hard no for me. Not worth the increased risk of SJS, even if that increased risk is based on weak evidence.

 

[clausewitz2]

I have seen neurologists titrate it pretty quickly but when the alternative to adequate dosing is "you might seize forever and die" I think it is easier to justify the trade-off.

 

[NickNaylor]

Agreed that neurologists seem less concerned about titration than psychiatrists. When I rotated on our EMU as an intern, patients on lamotrigine prior to their admission would be titrated back to their previous dose pretty rapidly. I have yet to come across as a psychiatrist that will do the same, though I'm sure they're out there.

 

[FlowRate]

Neurologists used to loading dose people and still not that many died of SJS.

They're inpatient, so they're monitored. More than half of the value of inpatient stays is faster titration of medication. (Again, because they're observed 24/7 and seen by a doctor at least once a day with one on call just in case.) That doesn't mean you should go straight to loading, but a slightly accelerated pace is probably fine.

I'm just having trouble thinking about why you'd feel so compelled that LTG was essential to a psychiatric disorder. Maybe if someone was convincingly only effectively treated by that med and had discontinued it two weeks prior.

 

[whopper]

I hate prescribing Lamictal for this very reason and I almost never start anyone on it.

It's cheap, it's one of the only cheap meds that treats Bipolar Disorder without causing weight gain, a feeling of being zombified, and required labs for ongoing use. Although the empirical data for it treating Bipolar Depression is arguable I've seen major benefits with it. The problem is the patient needs to be compliant and it takes weeks to get to a decent dosage. I've hardly ever seen anyone feel a benefit at anything less than 100 mg daily and at 100 mg daily they sometimes feel a weak benefit.. I didn't typically see that in Medicaid offices but in private practice offices I usually saw that happening.

Worst case scenario I saw was a neurologist put the patient on 400 mg daily as the starting dosage. I was more convinced the person did it cause they didn't know what they were doing vs doing a real risk/benefit analysis. (There were plenty of problems with the way that patient was treated including them dumping a patient onto my unit when the problem was neurological, then when it was established it was neurological even with one of the top people in that department saying so neurology tried to prevent us from sending her back. It literally got to the point where the head of psychiatry and the head of neurology had to force the neuro inpatient unit to take her back in). Luckily no Stevens Johnson, but she rotted in psychiatry for 3 months (literally) over a neurological problem. Yes I know. It was a $hit-show. I also couldn't discharge her because her GAF was a 5 and she was too dangerous (due to a neurological condition) to discharge, and I couldn't send her to the ER due to it being a COBRA violation. I told the departments that if this situation wasn't rectified I was going to resign, and I informed the patient's family to complain to the state medical board despite that my name was on the case because I myself was disgusted with how the hospital handled it and would've been fine with elaborating everything that happened to them with some people connected to the case having to answer for their actions or lack thereof.

For anyone "getting scared" of private practice because of my pet-peeves with it, well think about inpatient and this type of dung-hitting-the fan scenario happening. And for me stuff like this happened on the order of every few months.

(In the end the hospital backed me up when they investigated it and found out I was the only guy attending trying to do the right thing).

I wouldn't for psychiatric reasons fast-titrate Lamotrigine unless it was close. E.g. maybe 1.5 weeks per dosage instead of the usual 2 weeks. Neurology is different especially if the patient's seizures are dangerously out-of-control.

 

[Armadillos]

I still think some folks are underestimating just how bad it is for someone to get SJS, especially off a med with modest at best efficacy for bipolar which actually often ends up being prescribed for what would be better diagnosed as cluster B.

Don’t have time to look up, but I thought remember reading with rapid titration SJS risk can be as high as 1-10% (if someone has actual number, I may be way off). That’s an astronomically high risk when considering a devastating outcome, although you could easily still put 10 psychiatrists in a room who all tried rapid titration once, had it go fine and then feel overly comfortable doing something extremely reckless.

 

[Crayola227]

I think it's terrible, which is why I think rapid titration makes little sense for psych applications. I agree that's horrible and I hope no one is espousing otherwise.

Here's the thing. A dermatologist once told me, that while many don't probably fully appreciate this, not only is the skin its own organ, but it's also a big extension of the immune system, and a finnicky not-well-understood part at that. Just about everything shows up in skin, eventually. I mean, why do so many disparate viruses with varying and seemingly unrelated symptoms cause rash? It's a big immune organ.

As such, anything you ingest has the potential to trigger some nasty skin stuff. Drugs in particular are somewhat foreign agents to the body, and so they're best candidates for triggering immune weirdness and skin sx. Just about every drug has the potential to trigger SJS/TENS or DRESS. Some more than others for various reasons.

I was told that steady dose lamotrigine, even at high doses, isn't actually among the worst culprits for causing dangerous skin reactions. Keeping in mind that across the board we're still talking rare enough that people use them anyway.

What isn't well understood, is why it is that the rapidity of the change of concentration seems to be the trigger. Which means that people should also be cautious coming off it, but rarely are. Something about that change seems to be what sets the immune system, specifically in the skin, off. Fascinating. Why this drug more than others? Why isn't it dose-related? Ie, why is a slow titration from 400-->500 less likely to set it off than a rapid titration from 100-->200 ? No one knows.

I don't have data on this, but I know I've seen numbers and examples to compare.

So my personal conclusion is that the real danger in lamotrigine has to do with the change in plasma concentration over time, so go slow.

There's tons of things that patients could "do without" that we unhesitatingly give them every day, that could do something similarly horrible and irreversible or deadly, and I'm certain a lot of that has similar risk and probably examples that are even higher. Factor it into to management of anything, certainly. Anything in medicine that is an "exception" to business as usual gets more attention, and it should. That's not always the same as more dangerous.

 

[futuredo32]

I have had amazing success with this drug. Patients (and I ) love the low side effect profile but I titrate slowly.

 

[MLT2MT2DO]

Lamictal is an outpatient drug, imo. There's so much we have available for acute issues that I don't think a 5-7 day rapid titration risks would ever be acceptable over other alternatives (if "nothing else works" I hope DBT is in your FU plan). If you were sold on Lamictal being the answer, I'd start it inpatient along another mood stabilizer with the plan for the secondary mood stabilizer to only be transitory and have the patient follow up with their outpatient provider for continued titration.

Lamictal is a great med, it's just not what I'd consider an "inpatient med"

 

[Stagg737]

I've had an attending on the inpt unit go up to 100mg/day in 2 weeks. However, this was at a VA and the patient lived in a VA nursing home, so there would be regular monitoring and 3-4 f/up appointments in the first month. Given the right patient who will d/c into an environment where they could be monitored regularly I think it could probably be justified. Generally speaking though I don't think I'd be comfortable doing this on a psych patient and don't like using it for the general public because of the length of titration if there are compliance issues.

 

[Crayola227]

I've had an attending on the inpt unit go up to 100mg/day in 2 weeks. However, this was at a VA and the patient lived in a VA nursing home, so there would be regular monitoring and 3-4 f/up appointments in the first month. Given the right patient who will d/c into an environment where they could be monitored regularly I think it could probably be justified. Generally speaking though I don't think I'd be comfortable doing this on a psych patient and don't like using it for the general public because of the length of titration if there are compliance issues.

100mg/day in 2 weeks? So they ended up on 1400 mg of lamictal total? Or you mean they went up 100 mg/day every few days to end up on the target dose within 2 weeks? Was this a neuro patient or a psych patient? This sounds insane to me in a lot of ways.

 

[hamstergang]

100mg/day in 2 weeks? So they ended up on 1400 mg of lamictal total? Or you mean they went up 100 mg/day every few days to end up on the target dose within 2 weeks? Was this a neuro patient or a psych patient? This sounds insane to me in a lot of ways.

It reads to me that they went from 0 to 100mg daily over the course of 2 weeks.

 

[Stagg737]

100mg/day in 2 weeks? So they ended up on 1400 mg of lamictal total? Or you mean they went up 100 mg/day every few days to end up on the target dose within 2 weeks? Was this a neuro patient or a psych patient? This sounds insane to me in a lot of ways.

Patient restarted at nothing and was increased in 25mg increments every 3-4 days until they reached a total daily dose of 100mg by the end of their second week (inpatient psych unit).

 

[Crayola227]

wow what a difference missing "to" in that statement made.... thanks

 

[Attending1985]

I also get nervous prescribing Lamictal and don’t do it often. That being said some patients do seem to significantly benefit from it. Has anyone had a patient develop sjs?

 

[splik]

I also get nervous prescribing Lamictal and don’t do it often. That being said some patients do seem to significantly benefit from it. Has anyone had a patient develop sjs?

None of my pts have developed SJS from Lamictal but I have seen pts w/ Lamictal related SJS (also carbamazepine related TEN and DRESS). I once saw a pt who got a big payout after successfully suing GSK for his SJS. spent all the money on meth.

 

[lyla]

If you need a patient to improve that rapidly chances are you won’t be using lamotrigine to begin with.

 

[Attending1985]

None of my pts have developed SJS from Lamictal but I have seen pts w/ Lamictal related SJS (also carbamazepine related TEN and DRESS). I once saw a pt who got a big payout after successfully suing GSK for his SJS. spent all the money on meth.

On consult service?

 

[shahseh22]

What do yo guys tell to patient's regarding the rash? like what kind of a rash should they be wary of in lay mans terms? Down where I live so many of my pts live in bed bug infested quarters that they get panicked whenever they hear the word rash and immediately attribute to lamictal

 

[NickNaylor]

What do yo guys tell to patient's regarding the rash? like what kind of a rash should they be wary of in lay mans terms? Down where I live so many of my pts live in bed bug infested quarters that they get panicked whenever they hear the word rash and immediately attribute to lamictal

I tell patients to either call the clinic or report to an ED with ANY rash. Obviously there are some features that are higher risk for true SJS (e.g., rash involving mucosa, a rash proximal to the mouth/eyes, associated constitutional symptoms, etc.), however the patient cannot and should not be responsible for making the diagnosis. Based on incidence alone true SJS is fairly rare and even if a rash develops it's more likely to be something else, but given the risk involved I tend to be conservative.

 

[futuredo32]

The likelihood of SJS is extremely low.

 

[futuredo32]

What do yo guys tell to patient's regarding the rash? like what kind of a rash should they be wary of in lay mans terms? Down where I live so many of my pts live in bed bug infested quarters that they get panicked whenever they hear the word rash and immediately attribute to lamictal

I use my phone and show them Google images

 

[Mass Effect]

I tell patients to either call the clinic or report to an ED with ANY rash. Obviously there are some features that are higher risk for true SJS (e.g., rash involving mucosa, a rash proximal to the mouth/eyes, associated constitutional symptoms, etc.), however the patient cannot and should not be responsible for making the diagnosis. Based on incidence alone true SJS is fairly rare and even if a rash develops it's more likely to be something else, but given the risk involved I tend to be conservative.

I do the same. I'd rather the patient present to the ED than diagnose their own rash.

Here's a question though. If a rash is documented in the chart, do you ever use Lamictal again? I had a patient during residency who was documented to have a Lamictal rash once about 10 years before I met her, per her own report to a previous provider. My attending chose to use Lamictal due to failed trials of every other med and the side effect profile of Lamictal. I was very nervous about this but in the end, my attending was right, the patient tolerated this with no rash and she actually improved with it. As a new attending, I don't know if I would do what my attending did as it still makes me anxious, but I wonder if I'm being too rigid in thinking that once you get a rash even once, no Lamictal in the future.

Thoughts?

 

[NickNaylor]

I do the same. I'd rather the patient present to the ED than diagnose their own rash.

Here's a question though. If a rash is documented in the chart, do you ever use Lamictal again? I had a patient during residency who was documented to have a Lamictal rash once about 10 years before I met her, per her own report to a previous provider. My attending chose to use Lamictal due to failed trials of every other med and the side effect profile of Lamictal. I was very nervous about this but in the end, my attending was right, the patient tolerated this with no rash and she actually improved with it. As a new attending, I don't know if I would do what my attending did as it still makes me anxious, but I wonder if I'm being too rigid in thinking that once you get a rash even once, no Lamictal in the future.

Thoughts?

I think everyone will approach this differently. Again, rare things being rare, the most likely thing is that onset of a rash with lamotrigine is unlikely to be SJS. If there are no other options and/or the patient is interested in trying lamotrigine again, I don't think it's unreasonable to do another trial. That said, I think you need to extensively counsel the patient on the risks of SJS and, specifically, how that risk may be higher given that he/she already had a rash with a previous trial. You also should explicitly document all of that and document that they understand the risks. If the patient is willing to accept that risk and you otherwise have no clear evidence that the rash was truly SJS, I don't think another trial is off the table.

That said, there are plenty of people who take the same approach as you - i.e., any rash associated with the start or titration of lamotrigine = no lamotrigine at any point in the future. I personally think that's a little too rigid and may "disqualify" patients from not receiving lamotrigine even though there may actually be no reason to do so, but I think everyone will have a different comfort level with respect to taking on this risk. Ultimately, I think it's the patient's choice as to whether or not they accept that risk - your job is just to counsel them as extensively as you can and make sure that there's no clear contraindication to another trial (e.g., a patient clearly had SJS with a previous trial).