Difficult case (schizoaffective, FND, and extensive allergy list)

[When is graduation again?]

Hi all. So I have a difficult case that I wanted to put to the group. I have a young ACT patient with schizoaffective disorder, bipolar type resulting in many hospitalizations and very bad destruction of property, in the years before I took over his care. Throughout those years, he was tried on a variety of antipsychotics (risperidone, olanzapine, haldol, prolixin, invega, etc), but each time would manifest "allergies", which he states (and are listed in his medical record) typically as difficulty breathing. (of note: in addition to the antipsychotic allergies, he has listed allergies to ativan, cogentin, benadryl, and several vaccines. He's actually taken Ativan after this allergy was documented with no issues.) He was stabilized on clozapine at his last hospitalization and did well enough on it at first, but due to weight gain, sedation, and general resistance to medication, keeping him on it has been a nightmare. I also worry about the continued cognitive and functional decline associated with continued breakthrough psychosis because his baseline when medication compliant is actually pretty high.

So here's my dilemma. After working with him several months (it's been about a year now), I realized that his "allergies" were actually functional neurological conditions. At first, I believed they could be dystonic, but he continued to have these symptoms even on clozapine and with anticholinergics, and even stated a HTN medication caused dystonia at a later visit. After a period in which he stopped taking his medications and had a nonexistent clozapine level, he presented with obvious functional tremors/jerks and "body stuckness" which was a clearly fake, pseudo-paralysis in the setting of overt psychosis. At that time, I managed to convince him to restart clozapine, which caused resolution of FND and psychotic symptoms, but this cycle continues to repeat. I want to switch him to an LAI, but he has a listed allergy to every medication with an LAI (except maybe prolixin. This isn't listed as an allergy though he reported EPS effects, so I could maybe get away with re-attempting it.).

My questions for the group.

1) What approach would you take in this case? Is there anything that I should try differently?
2) Would you consider trialing a medication on his allergy list? If so, how would you approach it? Even though I'm 95% sure none are true allergies, I would prefer to avoid medical liability this early in my career.

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[littlefred]

Have you considered adding metformin or topiramate to his regimen while the patient is on clozapine? It can counter some of the metabolic side effects and help the patient be more compliant with it.

Good luck!

 

[Stagg737]

One of the things I learned in residency which I have seen quite frequently is that patients with significant chronic psychosis often misinterpret their physical symptoms and while something may be legitimately going on, their report is inaccurate. I'm not just talking about patients with leg pain thinking they had a tracker inserted. For example, 20-something year old patient on our unit kept reporting constipation every other day and staff was monitoring for BMs and she was having them regularly and normal sized. Turns out her "constipation" was anxiety exacerbations that improved with hydroxyzine.

For this guy with a million allergies, I'd expect something similar if he really believes what he's reporting in which case re-trialing some of the meds listed as "allergies" is completely reasonable, though I'd want to do it in a controlled setting (inpatient or IOP/PHP) in case it turns out one of them is a legit allergy. I'd also try and get a hold of the individuals/original documents of the docs who saw him and originally documented the allergies if possible, as they may be able to give you a better idea of whether it was just an adverse reaction or a true allergy that needs to be avoided. I know our system just lists every adverse reaction/hypersensitivity/etc under allergies, so an actual account of events leading up to documentation can be extremely helpful.

Also, any chance this guy is on the autism spectrum? I've seen a lot of people on the spectrum where meds just do weird/atypical stuff and they have reactions like this. Could be worth exploring in terms of determining resource availability.

 

[Merovinge]

Clozapine seems a good bet, can you have him come in daily to take the medication in a supervised setting (at least Mon-Friday)? Not sure what kind of ACT services you have. I would 100% make sure he is at least on Metformin and would consider an Ozempic type medication as well for the wt gain (ideally also seeing if he can get involved in a gym or other vigorous exercise).

I think if adherence is not possible with oral even with ACT support, any of the previous medications that worked the best would be fine to resume PO, ideally supervise at HLoC and then after demonstrating lack of allergic response and tolerance (Which may take this patient a bit longer) can convert to LAI with significant documentation about lack of allergy. I would not have any significant worries about liability if you are taking all those steps.

 

[Celexa]

Is there any possibility some of what you're seeing is catatonia? "stuckness" could potentially describe multiple catatonic features (posturing, ambitendency, negativism...). There's a small subset of patients who end up needing chronic benzos and this guy certainly has the back story for it. And if that's what it was, it might explain it why he reported something new/bad with some antipsychotics and if it is part of his primary psychiatric process, also why it gets better with cloz.

In terms of the allergies piece, they certainly don't sound like anaphylactic reactions and I think it's fair to rechallenege with clear documentation about why. If you really wanted to CYA you could have the patient see allergy although the logistics of that happening on a useful timeline are probably daunting.

 

[Sushirolls]

ECT can be an adjunct to antipsychotics in refractory cases.
But it requires ongoing maintenance treatments.
Definitely not a first line for Schiz, but some publications out there for adjunct role.

 

[comp1]

Hopefully your EMR can separate out adverse reactions from allergies. It's as important to update the "allergy" list when you find something incorrectly listed as it is to update it with reports of allergies. Schizophrenia is ultimately an ego-syntonic illness, so the taking of medication usually seems either unnecessary or actively harmful. Thus, functional symptom development should almost be expected. The clozapine symptoms are all common and well known. The others are more likely to be in the functional category. If you need to try meds in an observed setting, try an inpatient stay or PHP where they could administer an epi-pen in the 1 in a million possibility there's anything remotely organic to these complaints. After a brief oral trial, get on the LAI and remove the adverse reaction listing once demonstrably incorrect. Most importantly, get family as heavily involved as possible and educate on the likelihood versus remoteness of various side-effects.

 

[When is graduation again?]

Have you considered adding metformin or topiramate to his regimen while the patient is on clozapine? It can counter some of the metabolic side effects and help the patient be more compliant with it.

Good luck!

Yep. I placed him on metformin. Still assessing if it's having any impact on weight. I'd consider topamax, but he already reports a lot of cognitive issues associated with his illness, so I doubt he'd be willing to try it. I am considering a GLP 1 agonist or orlistat as fallbacks though.

 

[When is graduation again?]

One of the things I learned in residency which I have seen quite frequently is that patients with significant chronic psychosis often misinterpret their physical symptoms and while something may be legitimately going on, their report is inaccurate. I'm not just talking about patients with leg pain thinking they had a tracker inserted. For example, 20-something year old patient on our unit kept reporting constipation every other day and staff was monitoring for BMs and she was having them regularly and normal sized. Turns out her "constipation" was anxiety exacerbations that improved with hydroxyzine.

For this guy with a million allergies, I'd expect something similar if he really believes what he's reporting in which case re-trialing some of the meds listed as "allergies" is completely reasonable, though I'd want to do it in a controlled setting (inpatient or IOP/PHP) in case it turns out one of them is a legit allergy. I'd also try and get a hold of the individuals/original documents of the docs who saw him and originally documented the allergies if possible, as they may be able to give you a better idea of whether it was just an adverse reaction or a true allergy that needs to be avoided. I know our system just lists every adverse reaction/hypersensitivity/etc under allergies, so an actual account of events leading up to documentation can be extremely helpful.

Also, any chance this guy is on the autism spectrum? I've seen a lot of people on the spectrum where meds just do weird/atypical stuff and they have reactions like this. Could be worth exploring in terms of determining resource availability.

I agree. I'd love to retest him for risperdal or invega, if I can find a facilitate willing to admit him for re-trial. In regards to autism, he's not autistic. He has good social reciprocity, doesnt' have fixed routines/interests, and makes good eye contact. His symptoms didn't appear until his early 20s and even now he presents very well when med compliant with clozapine. He gets very psychotic when off meds and his overt FND symptoms only emerge when not med compliant.

 

[When is graduation again?]

Clozapine seems a good bet, can you have him come in daily to take the medication in a supervised setting (at least Mon-Friday)? Not sure what kind of ACT services you have. I would 100% make sure he is at least on Metformin and would consider an Ozempic type medication as well for the wt gain (ideally also seeing if he can get involved in a gym or other vigorous exercise).

I think if adherence is not possible with oral even with ACT support, any of the previous medications that worked the best would be fine to resume PO, ideally supervise at HLoC and then after demonstrating lack of allergic response and tolerance (Which may take this patient a bit longer) can convert to LAI with significant documentation about lack of allergy. I would not have any significant worries about liability if you are taking all those steps.

Thanks for the suggestions. We see him 2-3 times per week, but daily monitoring is unlikely to work. He's not reliable upon awakening and doesn't have reliable transportation. Plus, he wouldn't be willing to do it. I have him on Metformin and was considering Ozempic as backup if the metformin doesn't work, though family is against the idea of him taking diabetes medication, so I may run into an issue with that.

Also appreciate the reassurance on the liability front. After typing my OP and reading/responding to comments, I'm probably going to retry prolixin. At least, I have documented evidence for that being EPS rather than allergy to make it a bit of an easier case for him for re-trialing. It should also pose less metabolic risk than some of the alternatives.

 

[When is graduation again?]

Is there any possibility some of what you're seeing is catatonia? "stuckness" could potentially describe multiple catatonic features (posturing, ambitendency, negativism...). There's a small subset of patients who end up needing chronic benzos and this guy certainly has the back story for it. And if that's what it was, it might explain it why he reported something new/bad with some antipsychotics and if it is part of his primary psychiatric process, also why it gets better with cloz.

In terms of the allergies piece, they certainly don't sound like anaphylactic reactions and I think it's fair to rechallenege with clear documentation about why. If you really wanted to CYA you could have the patient see allergy although the logistics of that happening on a useful timeline are probably daunting.

Catatonia can cause a lot of weird things. I'll keep that in mind if he does it again. I don't think it's catatonia though, mainly because it presented as frank jerks (that are not present when he's distracted) and the "stuckness" was basically him walking to the door then saying "oh no, I'm falling", then him gingerly falling to the ground while cushioning his fall. He then sat there for a few minutes before I convinced him that he was fine and that it was likely psychogenic. It also only occurs after he stops taking medications, but he'll blame it on the meds even though they're out of his system.

The idea of finding any facility willing to allow him to re-trial meds without a hospitalization indication seems pretty daunting to be honest.

 

[Stagg737]

Yep. I placed him on metformin. Still assessing if it's having any impact on weight. I'd consider topamax, but he already reports a lot of cognitive issues associated with his illness, so I doubt he'd be willing to try it. I am considering a GLP 1 agonist or orlistat as fallbacks though.

If he's not on melatonin, start that as well. There's actually some okay evidence that it can help with metabolic side effects of antipsychotics, supposedly through downstream effects. I've actually found it helpful a couple of times and certainly less of an issue than starting other meds.

 

[whopper]

1-Tamoxifen. It's a highly effective and underused mood stabilizer. WTF Tamoxifen the chemotherapy med for breast cancer? Yes. One theory is because Estrogen is a potent mood stabilizer it may be exploiting estrogen-like effect.

Problem-because it's so unconventional insurance likely won't pay for it, you likely have no experience with it and everyone will be thinking WTF if you prescribe it.

2-The patient could literally just be phucked. I don't mean this in jest. This is what I call medical checkmate. Careful before you make that judgment. Some patients despite even being seen by the best doctors, nothing else can be done. Most doctors I've seen prematurely go to this decision.

3-Dig deep-try older antipsychotics if you have to do so. Even some of the typicals such as Loxatine aren't very strong D2 blockers.

 

[Celexa]

Yep. I placed him on metformin. Still assessing if it's having any impact on weight. I'd consider topamax, but he already reports a lot of cognitive issues associated with his illness, so I doubt he'd be willing to try it. I am considering a GLP 1 agonist or orlistat as fallbacks though.

I think you'd be more than justified clinically going straight to a glp-1 agonist if you're comfortable with that. I'd think if anything the issue would end up being insurance coverage. I'd most likely to pick up the phone and call the pcp to talk about it if the pt has one.

 

[splik]

I wouldn't conceptualize this as FND, but a manifestation of the underlying psychosis. It's called a disorder of willed action. The mechanism is pretty similar to auditory hallucinations, passivity phenomena, or delusions of thought interference. Interestingly, a small subset of patients who are referred to me with FND actually have a psychotic illness.

 

[When is graduation again?]

I wouldn't conceptualize this as FND, but a manifestation of the underlying psychosis. It's called a disorder of willed action. The mechanism is pretty similar to auditory hallucinations, passivity phenomena, or delusions of thought interference. Interestingly, a small subset of patients who are referred to me with FND actually have a psychotic illness.

Interesting. I've never heard that terminology used before. This is the 1st case I've seen of this, so I didn't even know where to look to begin finding an answer. Though I didn't know the terminology, I have de-facto conceptualized it as a sequela of the psychotic phenomena, which is why I have been prioritizing the antipsychotic treatment, since clozapine caused the disorder of willed action to remit.

Is there a resource you're aware of that covers psychotic symptoms outside of the typical DSM criteria? A lot of that knowledge seems to have been ignored in psychiatry education (at least where I trained) with the focus on DSMV and the historical elements of first rank symptoms.

 

[When is graduation again?]

1-Tamoxifen. It's a highly effective and underused mood stabilizer. WTF Tamoxifen the chemotherapy med for breast cancer? Yes. One theory is because Estrogen is a potent mood stabilizer it may be exploiting estrogen-like effect.

Problem-because it's so unconventional insurance likely won't pay for it, you likely have no experience with it and everyone will be thinking WTF if you prescribe it.

2-The patient could literally just be phucked. I don't mean this in jest. This is what I call medical checkmate. Careful before you make that judgment. Some patients despite even being seen by the best doctors, nothing else can be done. Most doctors I've seen prematurely go to this decision.

3-Dig deep-try older antipsychotics if you have to do so. Even some of the typicals such as Loxatine aren't very strong D2 blockers.

I have a few patients in the phucked camp, but I'm hoping he's not there yet. I will definitely be digging deeper into the toolbox for now. Unfortunately, he's one of those patients that will always find a reason to stop taking meds, so we'll see.

I haven't heard much about the use of tamoxifen for mood stabilization. I'll have to look that up.

 

[Celexa]

I think you've got at least a couple things to try (before you get to phucked). Some might not be logistically feasible, but at least can be explored

-cloz + glp-1 agonist which might be palatable to the pt
-you say he's schizoaffective--has lithium or other non antipsychotic mood stabilizers been tried? Is his psychosis manic in flavor?
-ECT as mentioned above
-re-challenge with the allegedly allergic meds

After a good college try and all of those, is prob when I'd admit defeat.

 

[whopper]

I have a few patients in the phucked camp, but I'm hoping he's not there yet. I

I used to work in a state mental hospital. These are usually the patients that have to be in a place long-term caused they're screwed in the sense that they're not expected to get better either at all or for a long-term usually well over a month. The problem was that most of the patients I had, within weeks I got better. The problem being that several state hospital doctors pretty much suck. No not all of them but a lot of them. E.g. schizophrenic on Risperidone 1 mg a day and the doctor doesn't raise the dose and the patient's been psychotic for years. I raised the dosage to eventually to 4 mg PO Q BID and not surprisingly the patient improved tremendously.

The above isn't a declaration that I'm such a great doctor. It's more that I was doing a job I should've been, and so many weren't. If you got a math teacher who knows the multiplication tables and the other math teachers don't that's not a testament that the 1 doctor who knows the tables is a great math teacher, just that the others are terrible. Another thing I noticed was that younger docs that were fresh graduates often times cared, were willing to work hard within a year or two left, and the lazy docs stayed.

A problem is state hospitals don't pay well and like the VA highly tolerate providers that aren't doing their job whether it's a doctor, nurse whatever. Such institutions have a reward system that doesn't get rid of people doing poor work, and makes it hard for superiors to get rid of ineffective workers, but also not keep doctors that are doing excellent work.

 

[whopper]

Only medication that's consistently showed significant improvement in studies when added to Clozapine is Amisulparide. It's not available in America except in IV form for N&V.

Someone could of course point out they can pull dozens of studies showing other meds that improve Clozapine. Yeah whatever. They're all stuff we already know works like adding Lithium of Depakote to an antipsychotic or a hit or miss study that only had a few people it in and when it was replicated it didn't work.

Of course if you have a Clozapine resistant patient try something else cause there could be a magic regimen you can find through trial and error, but except for Amisulparide, doing a Clozapine blood level, and what's already known that someone would've already tried before bouncing the problem off another doc (like Lithium or Depakote) studies won't point you in a direction. Like I said only med that really works well is one not in the USA except in IV form for N&V. Good old fashioned try another med starting with a mechanism not exploited first and then dig deeper can lead to further improvement but it's a grind. IF you're in a long-term situation do it.

 

[clozareal]

3-Dig deep-try older antipsychotics if you have to do so. Even some of the typicals such as Loxatine aren't very strong D2 blockers.

Loxitane/loxapine gets converted to amoxapine, which is a TCA. Theoretically can worsen mood episodes and potentially cause mania in someone with bipolar. I've also used perphenazine (Trilafon), Thioridazine (Mellaril), Trifluoperazine (Stelazine). Molindone is one of the only FGAs associated with weight loss. FGAs are notorious for inducing depressive episodes in those with bipolar.

You can also consider the non D2 antipsychotics, like lumateperone or pimavanserin.

These may not be true allergies, which would be a hypersensitivity reaction by the immune system. Dystonia is erroneously listed as an allergy all the time but it's not—it's an adverse reaction. Same with other extrapyramidal symptoms. If you're worried, you may want to consult with an allergist. For acute dystonia, you can start an antipsychotic with an anticholinergic for the first few weeks since the risk is highest in the first 5-10 days. If he says allergy to Benadryl and Benztropine, then try Artane (trihexyphenidyl). If he reports difficulty breathing on these meds, then break out your stethoscope and pulse oximeter to confirm.

The biggest bang for your buck is going to be clozapine + an LAI + an anticholinergic if EPS really is an issue.

 

[ObsequiousAplomb]

Loxitane/loxapine gets converted to amoxapine, which is a TCA. Theoretically can worsen mood episodes and potentially cause mania in someone with bipolar. I've also used perphenazine (Trilafon), Thioridazine (Mellaril), Trifluoperazine (Stelazine). Molindone is one of the only FGAs associated with weight loss. FGAs are notorious for inducing depressive episodes in those with bipolar.

You can also consider the non D2 antipsychotics, like lumateperone or pimavanserin.

These may not be true allergies, which would be a hypersensitivity reaction by the immune system. Dystonia is erroneously listed as an allergy all the time but it's not—it's an adverse reaction. Same with other extrapyramidal symptoms. If you're worried, you may want to consult with an allergist. For acute dystonia, you can start an antipsychotic with an anticholinergic for the first few weeks since the risk is highest in the first 5-10 days. If he says allergy to Benadryl and Benztropine, then try Artane (trihexyphenidyl). If he reports difficulty breathing on these meds, then break out your stethoscope and pulse oximeter to confirm.

The biggest bang for your buck is going to be clozapine + an LAI + an anticholinergic if EPS really is an issue.

I agree with most of what you said.

While loxapine can theoretically worsen bipolar disorder, it also has great both mood stabilizing and mood lifting properties, so is a fantastic choice for the right bipolar patient.

There's no good reason to add an anticholinergic to clozapine to prevent EPS. First, anticholinergics don't prevent dystonic reactions. Second, how would adding a less anticholinergic medication have any benefit to clozapine's anticholinergic properties compared to a minimally higher dose of clozapine? Yeah, it's an agonist at M4, but other than that it would do just fine on its own. The only thing adding cogentin will guarantee is extra constipation and a greater proportion of tachycardia.

 

[clozareal]

There's no good reason to add an anticholinergic to clozapine to prevent EPS. First, anticholinergics don't prevent dystonic reactions. Second, how would adding a less anticholinergic medication have any benefit to clozapine's anticholinergic properties compared to a minimally higher dose of clozapine? Yeah, it's an agonist at M4, but other than that it would do just fine on its own. The only thing adding cogentin will guarantee is extra constipation and a greater proportion of tachycardia.

Yeah agreed. You are right. No anticholinergic since clozapine has its own properties. I was thinking about LAI + anticholinergic.