Patient on Clozapine with SBO

[AD04]

I encountered an interesting (perplexing) case:

30-something yo male comes to the hospital for vomiting and abdominal pain and lack of gas / stool for several days. It got so bad he passed out before being brought to the ER. He was just DC from the psychiatric unit less than one month ago for schizoaffective disorder (bipolar type) and when unwell would be manic and paranoid. He failed Latuda. Haldol caused EPS. And was finally stable enough for DC on clozapine after several weeks. History of multiple admissions of psychiatric units, especially after clozapine was decreased. He's been on clozapine for about 2 years.

CT of abdomen was done and impression was partial / intermittent small bowel obstruction. Psychiatry was consulted for toxic lithium levels (around 2).

Home psychotropics were:
- klonopin 0.5mg BID
- lithium 450mg BID
- clozapine 400mg HS

Patient is NPO except PO medications. Surgery was consulted and he's being treated for SBO. He had no recent surgeries. He was placed on NG tube which provided some GI relief.

I stopped lithium as the levels were too high. I kept him on the klonopin. I'm mixed about what to do with clozapine. On one hand, clozapine was effective enough to get him out the psychiatric unit. On the other hand, I'm worried about SE of paralytic ileus despite the impression from radiology. If I switch, I'm thinking of switching to risperdal for less anticholinergic effects and less risk of paralytic ileus.

I looked through the consult textbooks (MGH, Fogel) and they had nothing about this. The Clozapine Handbook (excellent book btw) talks about paralytic ileus but doesn't talk about SBO.

I'll reach out to radiology to discuss differential of paralytic ileus and I'm thinking of switching to risperdal to be on the safe side from a medical POV.

How would you approach this differently?

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[Alemo]

What’s his clozapine level? Could he get by with a lower dose? What’s the bowel regimen like?

The handbook probably doesn’t talk about SBO because it’s a downstream effect of ileus. Just like the handbooks don’t talk about cardiac management of ventricular arrhythmias that may have been caused by psych meds. Unless there’s another more likely cause, the ileus probably caused the obstruction.

 

[wolfvgang22]

I encountered an interesting (perplexing) case:

30-something yo male comes to the hospital for vomiting and abdominal pain and lack of gas / stool for several days. It got so bad he passed out before being brought to the ER. He was just DC from the psychiatric unit less than one month ago for schizoaffective disorder (bipolar type) and when unwell would be manic and paranoid. He failed Latuda. Haldol caused EPS. And was finally stable enough for DC on clozapine after several weeks. History of multiple admissions of psychiatric units, especially after clozapine was decreased. He's been on clozapine for about 2 years.

CT of abdomen was done and impression was partial / intermittent small bowel obstruction. Psychiatry was consulted for toxic lithium levels (around 2).

Home psychotropics were:
- klonopin 0.5mg BID
- lithium 450mg BID
- clozapine 400mg HS

Patient is NPO except PO medications. Surgery was consulted and he's being treated for SBO. He had no recent surgeries. He was placed on NG tube which provided some GI relief.

I stopped lithium as the levels were too high. I kept him on the klonopin. I'm mixed about what to do with clozapine. On one hand, clozapine was effective enough to get him out the psychiatric unit. On the other hand, I'm worried about SE of paralytic ileus despite the impression from radiology. If I switch, I'm thinking of switching to risperdal for less anticholinergic effects and less risk of paralytic ileus.

I looked through the consult textbooks (MGH, Fogel) and they had nothing about this. The Clozapine Handbook (excellent book btw) talks about paralytic ileus but doesn't talk about SBO.

I'll reach out to radiology to discuss differential of paralytic ileus and I'm thinking of switching to risperdal to be on the safe side from a medical POV.

How would you approach this differently?

I think you are on the right track. I wouldn't waste time reaching out to radiology, clozapine is notorious for causing paralytic ileus and honestly the black box warning should be for that, not just the much more rare agranulocytosis in my opinion.

My approach patients like this is to 1. Consider reducing clozpine, and consider dividing the dose to BID. 2. Be sure the patient is on a bowel regimen. I've found miralax and lubriprostone particularly helpful in these patients. 3. Frequent monitoring because the risk of recurrence of ileus and SBO is high. 4. Be sure the patient had support with managing their medication and bowel regimen at home. Patients like this typically benefit from an ACT team seeing them weekly.

Risperidone is a good choice to switch to, and if you have concerns the patient cannot adhere to a bowel regimen I would just go ahead and switch while you have them inpatient. If the patient has recurrent constipation after making changes to clozapine and instituting a bowel regimen, I switch to Risperdone. Waiting results in bowel resection in my experience.

 

[forchinet121]

Would you stop clozapine immediately or taper? What dose would you start risperdal at?

 

[nexus73]

Is medication history latuda and haldol, and he’s never tried risperidone? That seems so strange.

 

[clausewitz2]

Is medication history latuda and haldol, and he’s never tried risperidone? That seems so strange.

Or olanzapine, that would be my go to in most cases if I absolutely had to stop someone's clozapine who had done well on it.

 

[forchinet121]

Or olanzapine, that would be my go to in most cases if I absolutely had to stop someone's clozapine who had done well on it.

But it’s also very anticholinergic isn’t that the point of stopping the clozapine

 

[Stagg737]

Agree with the above, the first thing is to check levels. If Clozapine is The med for the patient, split the dosing and optimize the bowel regimen. If needing another med I'd consider Olanzapine vs Risperidone if he hasn't been on it. Otherwise may need to figure out a way to make EPS tolerable. Mild to moderate EPS is likely better than death by ileus.

But it’s also very anticholinergic isn’t that the point of stopping the clozapine

It is, but less so than Clozapine and the most similar structurally and likely in terms of who it is effective for.

 

[calvnandhobbs68]

But it’s also very anticholinergic isn’t that the point of stopping the clozapine

Olanzapine is way less of a constipation/ileus issue in real life. Clozapine is notorious for this (the majority of patients actually end up with GI motility problems in one way or another) and we used to have basically everyone on a pretty decent bowel regimen if they were on clozapine.

 

[Stagg737]

Olanzapine is way less of a constipation/ileus issue in real life. Clozapine is notorious for this (the majority of patients actually end up with GI motility problems in one way or another) and we used to have basically everyone on a pretty decent bowel regimen if they were on clozapine.

This, everyone I have on Clozapine is also on a bowel regimen. Even if they have diarrhea when I start them, they at least get a PRN regimen. I also believe that the effects on GI motility should be a black box warning. In general, I'm far more concerned about the GI effects than agranulocytosis.

 

[clausewitz2]

This, everyone I have on Clozapine is also on a bowel regimen. Even if they have diarrhea when I start them, they at least get a PRN regimen. I also believe that the effects on GI motility should be a black box warning. In general, I'm far more concerned about the GI effects than agranulocytosis.

I don't start the bowel regimen automatically but you had best believe that every single follow-up appointment involves me asking them when they last had a bowel movement and how many days before that the previous one was. Very, very low threshold for adding something for sure.

EDIT: Worth noting that these days the only people I see who are on clozapine are people I am going to see monthly at least, more often every 2-3 weeks.

 

[G Sheb]

I think you're far to quick in wanting to stop clozapine.

How long has he been on clozapine? If he's been on it for a while, it's less likely to be responsible for the SBO. I'm not sure clozapine levels are all that helpful frankly.

 

[wolfvgang22]

I think you're far to quick in wanting to stop clozapine.

How long has he been on clozapine? If he's been on it for a while, it's less likely to be responsible for the SBO. I'm not sure clozapine levels are all that helpful frankly.

I'm also not worried about clozapine level that much, but it won't hurt to get a level. In the past I've had patients end up with a bowel resection from continuing clozapine, even though I reduced dose. Once someone has developed an ileus with clozapine I've found it tends to recur, even if they were on clozapine for a decade with no issues. Just my anecdotal experience with patients on clozapine. More research is certainly needed.

 

[Stagg737]

I think you're far to quick in wanting to stop clozapine.

How long has he been on clozapine? If he's been on it for a while, it's less likely to be responsible for the SBO. I'm not sure clozapine levels are all that helpful frankly.

Imo the level is more for trending to identify more acute changes in serum level without dose adjustments that could lead to SBO. For example, did they go from being a pack-a-day smoker to quitting? Sudden illness affecting metabolism? Other change in meds (Li level was high)? A random level probably isn't really helpful, but could be useful for comparing to a known baseline or creating one.

 

[Desired Member]

Obv i dont know the whole story but generally agree in these situations to ask about smoking cessation, infection, any new meds such as cipro, getting clozapine level. Also abrupt dicontinuation of clozapine can cause cholinergic rebound and delirium so if that is the decided course, may consider some type of lower level anticholinergic med, if only temporarily

 

[Evidence Based]

Agree with above that slow transit constipation -> ileus -> SBO is not uncommon on clozapine, and I also ask about it at every visit and treat aggressively. If he's been on clozapine for two years and it's clearly the most effective medication, I would hesitate to take him off it without exhausting other options. If he was not on any bowel reg previously, I'd definitely start one now (probably PEG 17g daily up to BID if needed, or Senna) and see how he does.There's no reason to think we can't at least try to manage this SE medically given clozapine's superior efficacy.

Also agree with getting a level, although it can be tricky to interpret inpatient if the patient is a heavy smoker and then stops while in the hospital, as this would make the level appear much higher than he's actually being exposed to at home.

 

[AD04]

Super busy so I didn't get to check the feedback until now. All good suggestions. Bowel regimen was just colace. In the psychiatric unit, he had no constipation so it was sufficient at the time. I didn't think clozapine level helped much in this case as it is a send-out lab and takes a few days for results so I skipped that. And even if clozapine levels were ok, I was still going to reduce or DC clozapine. To me, this had to be treated urgently as I didn't want the guy to get messed up bowel / resection.

I'll give you an update as to what happened. That morning that I posted, patient was still on clozapine. He didn't have bowel movement. I called up radiology and explained about possible ileus due to clozapine. The radiologist re-read the CT and said that it could be ileus. I stopped clozapine right there and then and replaced with risperdal. I wanted to reduce as much anticholinergic effects as possible. I'll worry about cholinergic rebound it if shows.

Next day, I saw the patient. He was in good spirits and fully oriented and ready to go home. I read through nursing note and saw he had 6 bowel movements. Coincidence that bowel movement came back on the first night he didn't have clozapine? I would have like him to stay longer so I can titrate up the risperdal. But he was sent home that day and will follow up outpatient. Now I cross my finger and hope he does ok. I'll explain to my partner what happened to his patient when he gets back.

For those who says ileus causes SBO, can you provide reference? From what I've read, they seem to be two different illnesses.

 

[forchinet121]

Super busy so I didn't get to check the feedback until now. All good suggestions. Bowel regimen was just colace. In the psychiatric unit, he had no constipation so it was sufficient at the time. I didn't think clozapine level helped much in this case as it is a send-out lab and takes a few days for results so I skipped that. And even if clozapine levels were ok, I was still going to reduce or DC clozapine. To me, this had to be treated urgently as I didn't want the guy to get messed up bowel / resection.

I'll give you an update as to what happened. That morning that I posted, patient was still on clozapine. He didn't have bowel movement. I called up radiology and explained about possible ileus due to clozapine. The radiologist re-read the CT and said that it could be ileus. I stopped clozapine right there and then and replaced with risperdal. I wanted to reduce as much anticholinergic effects as possible. I'll worry about cholinergic rebound it if shows.

Next day, I saw the patient. He was in good spirits and fully oriented and ready to go home. I read through nursing note and saw he had 6 bowel movements. Coincidence that bowel movement came back on the first night he didn't have clozapine? I would have like him to stay longer so I can titrate up the risperdal. But he was sent home that day and will follow up outpatient. Now I cross my finger and hope he does ok. I'll explain to my partner what happened to his patient when he gets back.

For those who says ileus causes SBO, can you provide reference? From what I've read, they seem to be two different illnesses.

Good work

 

[jbomba]

Or olanzapine, that would be my go to in most cases if I absolutely had to stop someone's clozapine who had done well on it.

What are your thoughts on loxapine in this case?

 

[Mad Jack]

I think you are on the right track. I wouldn't waste time reaching out to radiology, clozapine is notorious for causing paralytic ileus and honestly the black box warning should be for that, not just the much more rare agranulocytosis in my opinion.

My approach patients like this is to 1. Consider reducing clozpine, and consider dividing the dose to BID. 2. Be sure the patient is on a bowel regimen. I've found miralax and lubriprostone particularly helpful in these patients. 3. Frequent monitoring because the risk of recurrence of ileus and SBO is high. 4. Be sure the patient had support with managing their medication and bowel regimen at home. Patients like this typically benefit from an ACT team seeing them weekly.

Risperidone is a good choice to switch to, and if you have concerns the patient cannot adhere to a bowel regimen I would just go ahead and switch while you have them inpatient. If the patient has recurrent constipation after making changes to clozapine and instituting a bowel regimen, I switch to Risperdone. Waiting results in bowel resection in my experience.

I've heard of 3 clozapine deaths from ileus at my last training site and zero from agranulocytosis or neutropenia. Where's my bowel monitoring REMS!

I feel like in the acute phase I would stop clozapine, as this is a potentially fatal complication and clozapine will contribute to it not resolving. After it resolves, restart clozapine, incorporate rigorous bowel regimen, and monitor very carefully. That's just what my approach would be, can't say if it's right or wrong.

 

[Mad Jack]

Super busy so I didn't get to check the feedback until now. All good suggestions. Bowel regimen was just colace. In the psychiatric unit, he had no constipation so it was sufficient at the time. I didn't think clozapine level helped much in this case as it is a send-out lab and takes a few days for results so I skipped that. And even if clozapine levels were ok, I was still going to reduce or DC clozapine. To me, this had to be treated urgently as I didn't want the guy to get messed up bowel / resection.

I'll give you an update as to what happened. That morning that I posted, patient was still on clozapine. He didn't have bowel movement. I called up radiology and explained about possible ileus due to clozapine. The radiologist re-read the CT and said that it could be ileus. I stopped clozapine right there and then and replaced with risperdal. I wanted to reduce as much anticholinergic effects as possible. I'll worry about cholinergic rebound it if shows.

Next day, I saw the patient. He was in good spirits and fully oriented and ready to go home. I read through nursing note and saw he had 6 bowel movements. Coincidence that bowel movement came back on the first night he didn't have clozapine? I would have like him to stay longer so I can titrate up the risperdal. But he was sent home that day and will follow up outpatient. Now I cross my finger and hope he does ok. I'll explain to my partner what happened to his patient when he gets back.

For those who says ileus causes SBO, can you provide reference? From what I've read, they seem to be two different illnesses.

So clozapine-induced hypomotility basically just leads to stuff building up from a lack of speed of peristalsis. Eventually enough bulk will accumulate to form a mechanical obstruction of the bowels, forming a true SBO. Clozapine causes significant slowing of peristalsis, not true paralytic ileus, and therein lies its danger- there is enough movement to form a mechanical impaction.

This was edited for clarity and because I misused the word ileus in a slopoy manner.

Clozapine-induced gastrointestinal hypomotility: More than just constipation

A 60 y.o. male with longstanding paranoid schizophrenia was admitted from a local group home with abdominal pain and distention of several days in duration and vomiting for the previous 24 hours. He had been seen in the family practice clinic at this academic medical center on the day prior to...

meridian.allenpress.com

 

[Radetzky]

Ileus and SBO are entirely different diseases. Ileus does not lead to an SBO. They can both lead to intestinal ischemia and perforation tho which is where people might be getting confused. The other trouble is they can be impossible to differentiate sometimes, even with CT imaging.

 

[jbomba]

Ileus and SBO are entirely different diseases. Ileus does not lead to an SBO. They can both lead to intestinal ischemia and perforation tho which is where people might be getting confused. The other trouble is they can be impossible to differentiate sometimes, even with CT imaging.

What's your preferred bowel regimen?

 

[Clean7795]

It's all the same spectrum of disease. Obstruction covers both mechanical causes (e.g. adhesions, tumors) or nonmechanical causes (e.g. postop ileus). Ideally the radiologist should mention no transition point or mechanical cause identified... at which point it's arbitrary if you want to use "nonmechanical obstruction", "ileus", "functional obstruction", "slow transit" or another equivalent term. I prefer using the term ileus because it is less scary for other physicians and less likely to cause an unnecessary general surgery referral (and if it does they know it is probably not a surgical issue off the bat after reading my report).

A lot of downstream patient care/referrals are determined by whether I want to use a scary sounding word to descibe the disease process, or a vague/esoteric term few really understand.

 

[clausewitz2]

What are your thoughts on loxapine in this case?

It is not an agent I am tremendously experienced with outside of psychotic depressions, where I am trying to also harness the fact that it is metabolized to amoxapine. Given the similarities to clozapine it's worth a shot.

 

[Radetzky]

What's your preferred bowel regimen?

For an established ileus? Nothing.