Treatment resistant psychosis

[xavier2000]

Wanting some additional thoughts/critique of my thought process.

Male 40s schizoaffective, bipolar type

Got dc from long term psych admission (about 9 months) on total 300 Clozaril, Depakote with level low 50s, Lithium barely therapeutic. Briefly out at ALF then admitted for threats driven by continued psychosis. Clozaril slowly ticked up current admission few steps and the level is like 460 ng/ml now. Depakote increased x 2 with previous increase barely moving the needle to upper 50s. Recheck level pending. Still with delusions, hallucinations, some mood component to them related to his family - impression that he is separated from and feels loss of family.

My thinking is never felt pushing Clozaril much beyond current level - depending what you go with like 300-500 ng being top of the mark with higher levels no more effective with only significant ASE coming at higher doses.

My next step after see where at with VPA increase is getting Li more into therapeutic range.

My thinking is if that fails to add Haldol. I have not had much luck with Clozaril + other SGA in other cases.

Would appreciate thoughts and previous experiences.

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[Alemo]

Have you checked his clozapine and norcloz levels? Is he a smoker?
The “best” (limited) evidence for clozapine augmentation is aripiprazole. Maybe olanzapine.
Any medical problems or other prescriptions?

 

[clausewitz2]

Some evidence for lamotrigine augmentation of clozapine. Abilify is a good choice, though, as it may have some efficacy but even more importantly appears to reduce the metabolic side effects of clozapine.

What is the evidence you are citing that clozapine levels (outside the trivial case of 0) are at all useful for determining therapeutic level? Everything I have seen suggests they are only really good for monitoring for toxicity (if something sounds like it could have been a seizure and the level is >1000, you need to have darn good reasons to not reduce the dose). The same goes for Depakote - you are not treating seizures and I assume you don't think he might have hepatic encephalopathy. The level means very little.

Remember a lot of "treatment-resistant psychosis" occurs in people who have totally normal dopamine systems. This is someone who you might consider non-dopaminergic approaches; probably the most benign and best-supported is minocycline.

 

[dl2dp2]

ECT.

 

[Alemo]

Sorry, I totally missed the mention of the clozapine level. Sounds like you have a “therapeutic” trough level (in the sense that it’s likely non-toxic, but high enough to exert ostensibly its antipsychotic effect) even if that is not quite a valid concept as clausewitz pointed out.
What type of symptoms are you targeting? The aggression? Does that seem to be from delusions?

I’ve never heard of lamictal as augmentation in this situation but lamotrigine levels getting jacked up by enzyme inhibition from depakote sounds like a nightmare to deal with in someone as unstable as this

 

[Tapepsi]

ECT.

I agree with this. Have seen success with clozapine+ECT in previously clozapine-resistant patients especially when mood symptoms are present.

 

[whopper]

The “best” (limited) evidence for clozapine augmentation is aripiprazole. Maybe olanzapine.

The best data on augmentation is Amisulparide but it's not available in the USA. The data is quite strong on Amisulparide.

 

[Sushirolls]

ECT benefits for schizophrenia diminishes quickly unless you can do maintenance.
If logistics for maintenance ECT aren't there, might not be worth it.

But yeah, ECT

 

[whopper]

Henry Nasrallah would sometimes do consults for very difficult treatment resistant even to Clozapine cases. He often times recommended Reserpine despite the risks.

Another avenue is to try a typical of each family once atypicals were all tried and failed. E.g. almost no one gives out Thiothixene these days, but I've seen cases where this is the only one that works.

 

[clausewitz2]

Sorry, I totally missed the mention of the clozapine level. Sounds like you have a “therapeutic” trough level (in the sense that it’s likely non-toxic, but high enough to exert ostensibly its antipsychotic effect) even if that is not quite a valid concept as clausewitz pointed out.
What type of symptoms are you targeting? The aggression? Does that seem to be from delusions?

I’ve never heard of lamictal as augmentation in this situation but lamotrigine levels getting jacked up by enzyme inhibition from depakote sounds like a nightmare to deal with in someone as unstable as this

Absolutely a problem with Depakote, but then from the description Depakote seems to be pretty useless for this person.

A place to start re lamotrigine and clozapine: The efficacy of lamotrigine in clozapine-resistant schizophrenia: A systematic review and meta-analysis . A meta-analysis from 2017 suggested that lamotrigine had a significant positive effect but when removing extreme outliers this was not maintained. That suggests to me that it is going to be pretty clear whether someone is responding or not.

Topamax has also sometimes been effective in smallish trials but usually there is a high discontinuation rate.

 

[clausewitz2]

Henry Nasrallah would sometimes do consults for very difficult treatment resistant even to Clozapine cases. He often times recommended Reserpine despite the risks.

Another avenue is to try a typical of each family once atypicals were all tried and failed. E.g. almost no one gives out Thiothixene these days, but I've seen cases where this is the only one that works.

Reserpine is not a bad idea. I also just wanted to say I had a patient with pretty classic bipolar I who did fine on thiothixene alone and was quite stable (if mildly hypomanic continuously for years at a time) but who wound up hospitalized every time he got a new psychiatrist who was unfamiliar with Navane and put him on whatever new SGA had most recently come out.

Don't be those psychiatrists.

 

[xavier2000]

Thanks for the responses.

Regarding adding Haldol v Abilify: I recall several moons back I believe a study between augmenting with Haldol being more effective vs Abilify with less side effects.

On other points - I have had other patients come been stable on Navane for years and had to change as their local pharmacy could not get it anymore. These were outpatient folks. Did not want to approach it with possibility running into same problem if stabilized him then dc without being able to get the med.

The main issue in his few weeks in ALF between long term inpatient dc and current admission was stating he was suicidal and was going to hurt peers/staff at facility. Never acted on any of it. Staff even reported they did not feel threatened. While admitted he goes from isolating to being a tad overactive. No behaviors of concern. Thought disorder very prevalent. Talk to him and get basic flat responses someone with psychosis would give, and then his brain makes a wrong turn, some thought blocking comes. Delusions centered around concerns for his family or them being hurt then the religious one, Jesus or Devil comes - CAH to kill self, good v evil.

His current VPA level is in AM. I think insurance is ultimately going to push this guy out the door which is unfortunate.

 

[clausewitz2]

So this strikes me as possibly someone who just did not care for his ALF, is very familiar with how the mental health system works, and just repeatedly mashed the buttons that he knew would whisk him away somewhere else. What did he not like about the facility?

 

[psychapp121]

How can insurance get him out the door if he’s still symptomatic? Ultimately it’s your call to keep him until his symptoms remit right?

 

[Armadillos]

Is patient on any benzo? Seems like type of patient who likely going to be psychotic no matter what you do, but some BID klonopin can make it a lot less distressing.

 

[Madden007]

Make sure the patient is not catatonic. Subtle symptoms of catatonia are often mistaken for pure psychosis.

 

[Tapepsi]

Make sure the patient is not catatonic. Subtle symptoms of catatonia are often mistaken for pure psychosis.

I like this idea. Sometimes it’s worth hitting the reset button and trying a different approach.

Do you know (assuming he has previously been on them) how patient responded to benzos in the past? Might be worth trying an Ativan challenge. Especially during those periods when he seems to be isolating and exhibiting thought blocking.

 

[whopper]

Don't be those psychiatrists.

The problem is not just new psychiatrists dabbling with meds, but the prior psychiatrist that figured out that Navane could be the right med for the patient might've not documented well what was tried and what wasn't.

I've only seen 2 times my entire career where a psychiatrist other than myself cataloged the effect each med had on the patient, and educate the patient on the need to keep a record in case a new psychiatrist takes over. Pathetic isn't it? It should be a norm in our field to keep a ready-and-easily accessible catalog of each med tried on a patient.