Clozaril-induced "atypical" NMS

[DD214_DOC]

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I saw a few articles regarding two recent cases, one of which was mine, and an atypical presentation of NMS due to clozaril. I had read that clozaril-associated NMS presents with little to no rigidity in up to 50% of cases. I'm not sure how it was diagnosed as NMS in the absence of rigidity, but that's beside the point.

We have had two cases of individuals over 50 who developed an aspiration pneumonia shortly after initiation of clozaril which progresses to sepsis. In both cases, they developed tachycardia, fever, and AMS. One of them developed hypotension. Both were septic. The ICU team decided to try dantrolene, and symptoms resolved, so they naturally think the fever/tachy was due to clozaril, despite the absence of rigidity and a normal CK. I do not remember how dantrolene works, but I think it only affects skeletal muscle to reduce rigidity and has no effect on HR/BP/Fever, so I'm not really sure where the ICU team is coming from.

Any thoughts or similar experiences? I think the most likely explanation is that the dude is septic, which so far has not responded to 48 hours of broad-spec abx (more evidence the ICU cites to justify NMS)

 

[IAmAUser]

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[whopper]

Mentioned this before, I used to work in a state facility where plenty of people where on Clozaril because it was a long-term and forensic facility that housed some of the most serious patients in the sate, and I've never seen such a thing, and good thing too because I'd be in virgin-territory.

Can you provide a link to the articles? I'd be interested in reading them.

 

[billypilgrim37]

We had a semi-famous case of a guy who developed NMS on Clozaril. Semi-famous because about 60% of our residents got to take care of him at some time in the course of his extended stays inpatient and on the consult service at the medical hospital. I remember being on buddy call when we replaced an NG tube in him, and when we restarted the Clozaril at the begging of the cardiology team who were frustrated with him being delirious for four months in the ICU*. There was probably a 10 month gap in those two things, and they weren't even that close to the beginning or end of his treatment.

*cleared up the delirium in like 3 days. Would have bet a million dollars against this turning out well. dude was also on dialysis for like the past 10 years. If you felt comfortable restarting clozaril in a dude with clozaril-induced nms on dialysis who had been delirious in the ICU for four months, you are more of a cowboy than me.

 

[firedoor]

I don't know the article you're referring to, but myocarditis is one of the first things to rule out for someone with fever/tachy thought to be related to clozaril. there are plenty of other possibilities, but nms is not one of them for people on clozapine. if you told me he was also on other antipsychotics I might answer differently. when people talk about a distinct syndrome, and call it "atypical something totally different," I am always skeptical.
the er/medicine people at my hospital, otoh, often refuse to believe in/be willing to work up / treat nms when we have actual cases that we send them unless they are on death's door. it seems to be something people outside of psychiatry are just not very familiar with unfortunately.

I know exactly how you feel, but clozapine is not devoid of NMS risk; it is not special in that regard--though as you mentioned one can understand how myocarditis/fever (+/- neutropenia/sepsis) could be misdiagnosed as NMS in a patient on clozaril.

 

[IAmAUser]

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[kugel]

From the Fazaclo website, pg 16:
There have been several reported cases of NMS in patients receiving clozapine alone or in
combination with lithium or other CNS-active agents.

 

[DD214_DOC]

Yes, those are the articles.

I believe we finally convinced the ICU team to look at other possibilities rather than hanging their hat on NMS. While on call, I actually went ot ICU and literally watched the patient have an autonomic, "fit" before my eyes. His Tm climbed from 99 to 103.1 within 15-20 minutes and was tachycardic, hypertensive and tachypneic. This was all in the absence of rigidity or elevated CK. They administered dantrolene which had no effect this time.

It was quite fascinating to observe.