NMS

[Attending1985]

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I have a 61 year old patient with schizophrenia. I was not in the office to see the patient but his therapist called me concerned that he was incontinent (some at baseline but worse) and his mental status was changed from previous visits. He was less communicative and slightly confused. He was noted to be sweating. At baseline, his cognition is impaired. Around a month ago I switched him from Zyprexa to Loxapine. Two weeks ago I increased his Loxapine from 15 mg to 20 mg and stopped his Zyprexa (was cross titrating). I was concerned about NMS to I sent him to the ED. WBC was normal. CK was normal. CMP was normal. BP was slightly elevated 144/89 (His normal BP is around 120/80). Pulse was 72. RR was 20. He was afebrile. UA was negative. Tremor was noted to be pronounced (has a tremor at baseline). He was communicative per ER doc's note. ER Doc did not note rigidity. CT scanned his abdomen. He was complaining of nausea and abdominal pain for the past week. Gave him some fluids and sent him home.

I have never seen, only read about NMS. Is that any chance this is a mild, burgeoning NMS?

 

[WisNeuro]

What other meds is he on? Also, is this longstanding schizophrenia, no suggestion of Lewy Body?

 

[Attending1985]

No suggestion of Lewy body. He has Parkinsonism but it was felt to be secondary to neuroleptics. He has been diagnosed with chronic psychosis since early adulthood. He's on Remeron, metformin and Depakote.

 

[WisNeuro]

Ah ok, I was going to say, we've seen it sometimes in patients who are also prescribed carbidopa/levodopa and have cognitive impairment and start forgetting their doses, as rapid drop in levodopa can cause it. Still see the occasional missing of the LBD diagnosis, but that's more rare.

As for NMS, in the rare cases we see it, it's severe enough that they are hospitalized. Haven't seen a mild case.

 

[Attending1985]

Could the nausea and swearing represent Dysautonomia? Maybe not quite nms but neuroleptic toxicity.

 

[Mtnbiker]

Could the nausea and swearing represent Dysautonomia? Maybe not quite nms but neuroleptic toxicity.

Loxapine may have enhanced the serotonergic effect of Remeron. This could result in a serotonin syndrome where you would see sweating, dysautonomia, MS changes, diarrhea, shivers and of course the classic hyperreflexia.

 

[Attending1985]

Thanks I will keep that in mind. Should’ve stopped the remeron. Was weaning him off of Paxil and didn’t want to make too many changes at once.

 

[splik]

Loxapine may have enhanced the serotonergic effect of Remeron. This could result in a serotonin syndrome where you would see sweating, dysautonomia, MS changes, diarrhea, shivers and of course the classic hyperreflexia.

mirtazapine isn't serotonergic!

 

[splik]

This does not meet criteria for NMS. No fever, it ain't NMS. Not only that there's no rigidity, catatonia, normal white count, normal CK etc.
serotonin toxicity would be more likely but would need full med list. would be unlikely with loxapine and mirtazapine (and as I mentioned mirtazapine is not serotonergic)

 

[Attending1985]

This does not meet criteria for NMS. No fever, it ain't NMS. Not only that there's no rigidity, catatonia, normal white count, normal CK etc.
serotonin toxicity would be more likely but would need full med list. would be unlikely with loxapine and mirtazapine (and as I mentioned mirtazapine is not serotonergic)

Thanks. There’s a spectrum of serotonergic toxicity. I’ve seen patients with myoclonus who never get serotonin syndrome. Do you think this could be similar? Toxicity but not fulminant nms?

 

[Neuro111]

Well constipation can cause delirium in the elderly. What did the CT Abd show?

 

[Attending1985]

Well constipation can cause delirium in the elderly. What did the CT Abd show?

Mild/mod stool burden

 

[clozareal]

Probably not serotonin toxicity. mirtazapine is a 5HT2A antagonist, which is the antidote to serotonin toxicity (same MOA of cyproheptadine). If questioning, use the Hunter's Serotonin Toxicity Criteria.

As splik said, not NMS as no fever or rigidity, normal CK, normal WBC, only other lab to consider is ferritin (usually <6 in NMS), but there's not enough pretest probability for it so wouldn't be useful anyways

What about hyperammonemia from Depakote? Tremor plus AMS in someone on VPA could cause this. I would get an ammonia level.

 

[clausewitz2]

To join the chorus, mirtazapine is so clearly lacking capacity to increase intrasynaptic serotonin levels that co-administration with MAOIs is perfectly safe.

Any chance he usually drinks more alcohol than he lets on and cut back/stopped recently? Common things are common.

 

[AD04]

To join the chorus, mirtazapine is so clearly lacking capacity to increase intrasynaptic serotonin levels that co-administration with MAOIs is perfectly safe.

There is no mention of this in Stahl's. In fact, he warns about serotonin syndrome. Can you provide literature about this?

 

[clausewitz2]

There is no mention of this in Stahl's. In fact, he warns about serotonin syndrome. Can you provide literature about this?

Sure:

PubMed

PubMed® comprises more than 38 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites.

www.ncbi.nlm.nih.gov

As noted above, mirtazapine interacts with some sertonin receptors but simply does not increase intrasynaptic serotonin. It has no effect on reuptake or release. It is not a 5HT agonist. That is just not the mechanism. There have never been any cases of ST/SS with mirtazapine overdose.

I don't hate on Stephen Stahl like some people but you really should not take his word as law, and I would bet a large sum of money that if you asked him in person he would say something very different than what he is willing to say in a book that might get him sued.

 

[PsyDr]

When you say Parkinsonisms, does that encompass gait?

Bit of a stretch, but NPH might be a consideration (ie, wet, wacky, walking).

 

[WisNeuro]

When you say Parkinsonisms, does that encompass gait?

Bit of a stretch, but NPH might be a consideration (ie, wet, wacky, walking).

Possible, diagnosis could be tough if they are only relying on imaging as the ventricular enlargement would be common in chronic psychosis alone.

 

[Attending1985]

To join the chorus, mirtazapine is so clearly lacking capacity to increase intrasynaptic serotonin levels that co-administration with MAOIs is perfectly safe.

Any chance he usually drinks more alcohol than he lets on and cut back/stopped recently? Common things are common.

This could be it. He lives in a group home so you would think they would know but I wouldn’t be surprised.

 

[theduderino]

what are people's thoughts about cross-titration of anti-psychotics?

Unless it's clozapine I usually just stop one and start the other at a reasonable dose. This is the usual practice at my institution with the rationale that cross-titrating muddies the water a bit in terms of s/e (e.g additive EPS with multiple agents, additive akathisia) that makes it difficult to find an appropriate dose of the new agent.

 

[WisNeuro]

This could be it. He lives in a group home so you would think they would know but I wouldn’t be surprised.

Group homes vary quite wildly in terms of the oversight they enact on residents. Nothing surprises me about group homes in terms of substance use these days.