Withdrawal and Antipsychotics

[clement]

For those that may be especially familiar with meth, etoh, and opiate laden correctional settings where there is a lot state hospital pt cross pollination…

When the jail culture is to aggressively treat withdrawal with buprenorphine (frequently transitioning to sublocade) and to schedule Librium tapers… by a separate addiction service (often pharmacists or internists)…

Do you tend to let the acute w/d pass and then resume their Zyprexa 20 bid, offer lower doses to start, or offer prns until w/d is complete?

In this setting there is also a lot of pressure to resume their psychotropics and not wait it out. Usually they have some residual chronic or acute on chronic mood or psychotic sx…complicated by recent substance use. In the community in a monitored medical setting… I tend to wait out the acute w/d tx if they are not exhibiting hyperactive delirium w/ acute agitation or acutely psychotic or manic. Most are somewhere between intoxication and w/d when we see them in jail.

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[ObsequiousAplomb]

Which combination scares you more?

A) Librium taper, buprenorphine taper, high dose antipsychotics
B) recreational intravenous fentanyl use, severe alcoholism, high dose antipsychotics

Realistically, if the patient population is as heavy of a polysubstance user as the prison/state hospital crowd, much of their behavior is related to no longer having access to their substances of choice.

Zyprexa 20 BID has its place, and it is a small subset of the population where this is chronically justifiable (acutely, much easier). The most important part of what I'm seeing that you're talking about is whether or not that specific part is okay. Because I would never stop Zyprexa 10 daily while treating someone withdrawing. If someone has really needed Zyprexa 20 BID for years the rebound would be unpleasant.

 

[Celexa]

At first I thought you were asking if you should *start* antipsychotics and I was confused why you would start antipsychotics in someone actively withdrawing. Then I realized you're asking about chronic meds? Why would you hold someone's chronic med during withdrawal? They already have enough reasons to be miserable and you can't make many decisions about what to do with their chronic meds during that time anyway. Better to leave fewer variables changed and sort it out when they're past withdrawal.

 

[clement]

At first I thought you were asking if you should *start* antipsychotics and I was confused why you would start antipsychotics in someone actively withdrawing. Then I realized you're asking about chronic meds? Why would you hold someone's chronic med during withdrawal? They already have enough reasons to be miserable and you can't make many decisions about what to do with their chronic meds during that time anyway. Better to leave fewer variables changed and sort it out when they're past withdrawal.

No definitely not start new meds. In training I saw various perspectives on this between CL, ER, addictions settings and even pal care & hospice settings (treating withdrawal but needing to address pain).

Of course I wouldn’t withhold tx for a truly ill individual with a chronic history…but there is a fuzzy middle ground with a lot of these pts in correctional settings who basically exist high every day of their lives, get the schizo-x diagnosis in the community…and are frequently arrested somewhere between withdrawal and intoxication… it’s impossible to tease apart even if there is some primary psychotic or affective illness exacerbation in the mix. The internist or family med or pharmacist led addiction team tends to see them first, blasts them with benzos or buprenorphine, no one knows for the life of them when they last took their Zyprexa 20bid, good luck getting a pharmacy name out of anyone, and the culture is to expedite tx regardless of how dope sick.

 

[aim-agm]

No definitely not start new meds. In training I saw various perspectives on this between CL, ER, addictions settings and even pal care & hospice settings (treating withdrawal but needing to address pain).

Of course I wouldn’t withhold tx for a truly ill individual with a chronic history…but there is a fuzzy middle ground with a lot of these pts in correctional settings who basically exist high every day of their lives, get the schizo-x diagnosis in the community…and are frequently arrested somewhere between withdrawal and intoxication… it’s impossible to tease apart even if there is some primary psychotic or affective illness exacerbation in the mix. The internist or family med or pharmacist led addiction team tends to see them first, blasts them with benzos or buprenorphine, no one knows for the life of them when they last took their Zyprexa 20bid, good luck getting a pharmacy name out of anyone, and the culture is to expedite tx regardless of how dope sick.

I think this is the key point. While there are significant potential consequences of suddenly stopping high dose olanzapine, particularly if they are also having alcohol withdrawal and opioid withdrawal, you can correct those by just giving the olanzapine.

You aren't supposed to IM olanzapine with a benzodiazepine because of potentially fatal cardiorespiratory suppression. That doesn't really apply to PO normally, but throwing in a mu-opioid agonist and a benzodiazepine being started at the same time makes the situation not normal. Also, if they haven't gotten olanzapine in a while, buprenorphine (sedative)+chlordiazepoxide (sedative)+40 mg olanzapine (massive sedative)= potential for severe sedation.

Also, olanzapine lowers seizure threshold. Patients are at increased risk for seizure given alcohol (and who knows what else) withdrawal.

So, in the interest of not killing the patient, I think it is reasonable to wait and see.

 

[clausewitz2]

I think this is the key point. While there are significant potential consequences of suddenly stopping high dose olanzapine, particularly if they are also having alcohol withdrawal and opioid withdrawal, you can correct those by just giving the olanzapine.

You aren't supposed to IM olanzapine with a benzodiazepine because of potentially fatal cardiorespiratory suppression. That doesn't really apply to PO normally, but throwing in a mu-opioid agonist and a benzodiazepine being started at the same time makes the situation not normal. Also, if they haven't gotten olanzapine in a while, buprenorphine (sedative)+chlordiazepoxide (sedative)+40 mg olanzapine (massive sedative)= potential for severe sedation.

Also, olanzapine lowers seizure threshold. Patients are at increased risk for seizure given alcohol (and who knows what else) withdrawal.

So, in the interest of not killing the patient, I think it is reasonable to wait and see.

Presumably if someone is getting large enough doses of a BZD to be worried about all this, the changes of a seizure from GABAergic withdrawal is pretty low, no?

Interestingly since the warning about the IM olanzapine + BZD combo was added to the prescribing information, when people have examined this empirically we are looking at an extremely low likelihood of it happening. Money quote from one such paper from 2018:

"Ninety-one instances of the drug combination were discovered, with no serious adverse events following administration. Of these 91 patients, 41 received both medications within 60 minutes of each other. No instances of hypotension, bradycardia, bradypnea, or oxygen desaturation occurred following administration. The literature review yielded 1 randomized, placebo-controlled clinical trial, 3 retrospective chart reviews, and several case studies."

 

[Celexa]

No definitely not start new meds. In training I saw various perspectives on this between CL, ER, addictions settings and even pal care & hospice settings (treating withdrawal but needing to address pain).

Of course I wouldn’t withhold tx for a truly ill individual with a chronic history…but there is a fuzzy middle ground with a lot of these pts in correctional settings who basically exist high every day of their lives, get the schizo-x diagnosis in the community…and are frequently arrested somewhere between withdrawal and intoxication… it’s impossible to tease apart even if there is some primary psychotic or affective illness exacerbation in the mix. The internist or family med or pharmacist led addiction team tends to see them first, blasts them with benzos or buprenorphine, no one knows for the life of them when they last took their Zyprexa 20bid, good luck getting a pharmacy name out of anyone, and the culture is to expedite tx regardless of how dope sick.

Oh I see. No, I wouldn't restart high dose antipsychotics if the most likely scenario is they weren't taking any prior to presentation. However, I would continue them if I had good reason to think they were taking them regardless of if I suspected the underlying diagnosis was nonsense.

 

[aim-agm]

Presumably if someone is getting large enough doses of a BZD to be worried about all this, the changes of a seizure from GABAergic withdrawal is pretty low, no?

Interestingly since the warning about the IM olanzapine + BZD combo was added to the prescribing information, when people have examined this empirically we are looking at an extremely low likelihood of it happening. Money quote from one such paper from 2018:

"Ninety-one instances of the drug combination were discovered, with no serious adverse events following administration. Of these 91 patients, 41 received both medications within 60 minutes of each other. No instances of hypotension, bradycardia, bradypnea, or oxygen desaturation occurred following administration. The literature review yielded 1 randomized, placebo-controlled clinical trial, 3 retrospective chart reviews, and several case studies."

It doesn't sound like these people are practicing with thought and consideration, and can be reliably expected to get doses right. A plan would have to take into account that the benzodiazepines might be over- or under-dosed

My understanding is that the olanzapine-benzodiazepine interaction is rarely clinically significant...but if something bad does happen in this case it would probably be pinned on it (i.e. if patient dies lawyer would saw "well of course its @clement 's fault for giving olanzapine and benzodiazepine") no matter how factually or scientifically incorrect that might be.

 

[ObsequiousAplomb]

As far as I recall, the IM olanzapine + Ativan combo is actually safer than a B52. Don't know where I came to that conclusion, but I think it was a trivia question once or something.

Of course, as with most things that turn out to not be true, we just avoid them to avoid looking like we don't know something to the people who don't know.

 

[clement]

It doesn't sound like these people are practicing with thought and consideration, and can be reliably expected to get doses right. A plan would have to take into account that the benzodiazepines might be over- or under-dosed

My understanding is that the olanzapine-benzodiazepine interaction is rarely clinically significant...but if something bad does happen in this case it would probably be pinned on it (i.e. if patient dies lawyer would saw "well of course its @clement 's fault for giving olanzapine and benzodiazepine") no matter how factually or scientifically incorrect that might be.

This combo in PO doses that don’t violate a reasonable standard of care has never been a huge worry for me. I had a bunch of attendings as a resident a decade + ago who didn’t buy the IM combo “hysteria” but most graduates in my class were deathly afraid of it. Mind you, anecdotally I routinely saw EM docs blasting IM Zyprexa with Ativan up the wazoo but that was pre opioid madness too.

 

[clement]

Which combination scares you more?

A) Librium taper, buprenorphine taper, high dose antipsychotics
B) recreational intravenous fentanyl use, severe alcoholism, high dose antipsychotics

Realistically, if the patient population is as heavy of a polysubstance user as the prison/state hospital crowd, much of their behavior is related to no longer having access to their substances of choice.

Zyprexa 20 BID has its place, and it is a small subset of the population where this is chronically justifiable (acutely, much easier). The most important part of what I'm seeing that you're talking about is whether or not that specific part is okay. Because I would never stop Zyprexa 10 daily while treating someone withdrawing. If someone has really needed Zyprexa 20 BID for years the rebound would be unpleasant.

Yea this population often reports what they were last RX’d 2 years ago in a state hospital and not what they were actually taking (not taking) before arrest, withdrawal, and the snowstorms that ensue.

 

[ClosetCentrist]

Just chiming in here on the IM olanzapine and benzo thing and how overblown it is. The combo is actually not unusual in ED care outside of the US. There are a few papers out of Australia that were looking at using IV olanzapine for acute agitation. The baseline treatment that everyone got before the olanzapine? IM/IV midazolam.

 

[Merovinge]

On a related topic, are people using Precedex these days for acute agitation in the ED? I was just hearing murmurs of this when I left adult residency for fellowship, it seemed really promising compared to the B52 and such.

 

[Stagg737]

On a related topic, are people using Precedex these days for acute agitation in the ED? I was just hearing murmurs of this when I left adult residency for fellowship, it seemed really promising compared to the B52 and such.

Where I'm at the ED only uses it when the patient is getting admitted to one of the ICUs where they can continue the precedex. We do occasionally have to use it for the severely agitated who won't calm down and get aggressive (most recently a guy with TBI/anoxic brain injury after being found hanging), but those patients also get transferred to ICU if on the medical floors.

 

[comp1]

I also tend to agree that olanzapine and benzodiazepines IM aren't horrifically more dangerous than haldol/benadryl/Ativan in reality. However, also in reality, administration of medications for emergent agitation is fraught with risk in general. You just don't want to put yourself up to legal liability because there's also not some massive literature supporting the use of olanzapine and benzodiazepines IM as superior, just limited literature saying it probably doesn't kill people more often than other IMs. FDA warnings, particularly when there are other options, are catnip to trial lawyers. If we as a field want to do this, we need to advocate for the FDA to remove the warning.

 

[clausewitz2]

I also tend to agree that olanzapine and benzodiazepines IM aren't horrifically more dangerous than haldol/benadryl/Ativan in reality. However, also in reality, administration of medications for emergent agitation is fraught with risk in general. You just don't want to put yourself up to legal liability because there's also not some massive literature supporting the use of olanzapine and benzodiazepines IM as superior, just limited literature saying it probably doesn't kill people more often than other IMs. FDA warnings, particularly when there are other options, are catnip to trial lawyers. If we as a field want to do this, we need to advocate for the FDA to remove the warning.

Oh yeah, no shade on people who opt against it because there's other options and they don't want to get sued. I just thought it was interesting because in my training there was this drumbeat of "this combo is super dangerous" and it turns out the answer is "....legally"

 

[Cath Up]

Sort of related-

When we give one time doses of antipsychotics for psychotic agitation, APART from any histamine/acetylcholine blockade, what is its mechanism? I have heard the term neurolepsis thrown around, but I don’t understand how any meaningful core anti-psychosis activity would be taking place given antipsychotics typically take at least a week to really begin to take effect. Are we blocking NET and/or DAT In the frontal lobe to inhibit movement planning? Amygdala inhibition somehow? Why does it ever work better compared to snowing people with stronger CNS depressants?

I’d expect that no one really knows for sure but would like to think how this is conceptualized by others.

 

[clausewitz2]

Sort of related-

When we give one time doses of antipsychotics for psychotic agitation, APART from any histamine/acetylcholine blockade, what is its mechanism? I have heard the term neurolepsis thrown around, but I don’t understand how any meaningful core anti-psychosis activity would be taking place given antipsychotics typically take at least a week to really begin to take effect. Are we blocking NET and/or DAT In the frontal lobe to inhibit movement planning? Amygdala inhibition somehow? Why does it ever work better compared to snowing people with stronger CNS depressants?

I’d expect that no one really knows for sure but would like to think how this is conceptualized by others.

These medications were originally developed for use as anesthetic agents so the very first clinical use was in one-off dosing. Neurolepsis never referred to 'anti-psychotic activity' but to the subjective reduction in drive and behavioral output people experienced. If I had to hand wave an explanation I think it is more likely an issue of dopamine blockade reducing the magnitude of salience/reward expectancies globally.

It is less about snowing people to stop them wilding out, and more about making it not seem worth the effort. There is a reason people on high doses of these things are globally apathetic. The hope with therapeutic dosing is that you make the very insistent and urgent seeming problematic thoughts and perceptual experiences less compelling without abolishing drive for everything, but that doesn't always work out.

Neurolepsis is about that abolition of drive, the 'seizing of the nerves'.

 

[Cath Up]

These medications were originally developed for use as anesthetic agents so the very first clinical use was in one-off dosing. Neurolepsis never referred to 'anti-psychotic activity' but to the subjective reduction in drive and behavioral output people experienced. If I had to hand wave an explanation I think it is more likely an issue of dopamine blockade reducing the magnitude of salience/reward expectancies globally.

It is less about snowing people to stop them wilding out, and more about making it not seem worth the effort. There is a reason people on high doses of these things are globally apathetic. The hope with therapeutic dosing is that you make the very insistent and urgent seeming problematic thoughts and perceptual experiences less compelling without abolishing drive for everything, but that doesn't always work out.

Neurolepsis is about that abolition of drive, the 'seizing of the nerves'.

Thank you!!!

 

[ClosetCentrist]

Sort of related-

When we give one time doses of antipsychotics for psychotic agitation, APART from any histamine/acetylcholine blockade, what is its mechanism? I have heard the term neurolepsis thrown around, but I don’t understand how any meaningful core anti-psychosis activity would be taking place given antipsychotics typically take at least a week to really begin to take effect.

I think this is a misconception - we see effects sooner than 7 days in.

See: The “delayed onset” of antipsychotic action — an idea whose time has come and gone