Seroquel vs. Haldol for delirium

[MDchouette]

The Medicine and Psych services at my medical school differ in how they treat delirium -- Psych tends to use Haldol, while the IM docs use Seroquel. I am biased to trust the Psych docs, but I (a newly minted MS4) don't know the research on this. I'm wondering about the opinions of the psych docs and residents on this forum.

I think of delirium as an anticholinergic and dopaminergic phenomenon, so choosing Seroquel over Haldol doesn't make sense to me (other than to decrease the chance of EPS).

Is there an article that you all would recommend?

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[kugel]

As a med student, it's acceptable and encouraged to ask your medicine residents and attendings why they use Seroquel. You can tell them you looked it up in the Wash Manual of Medical Therapeutics and it said (pg 9 of 31st edition) that Haldol is considered the first choice. Be sure that whatever you quote you did look up. To stroke egos and get a more useful response, tell them that you suspect the info in your books is based on old info and you're sure they are using more recent primary publications, so you'd like to know where to read more about their decision to use Seroquel, and that you hope you can even convince the stodgy psychiatrists to utilize this newer information.

Please let us know what you get.

 

[maranatha]

The Medicine and Psych services at my medical school differ in how they treat delirium -- Psych tends to use Haldol, while the IM docs use Seroquel. I am biased to trust the Psych docs, but I (a newly minted MS4) don't know the research on this. I'm wondering about the opinions of the psych docs and residents on this forum.

I think of delirium as an anticholinergic and dopaminergic phenomenon, so choosing Seroquel over Haldol doesn't make sense to me (other than to decrease the chance of EPS).

Is there an article that you all would recommend?

In theory, you are correct regarding Haldol (i.e. with regards the anticholinergic properties, etc...), which is part of the reason a lot of psychiatry services tend to use it. Haldol is also nice because of the multi-route forms with PO, IM, or IV. Haldol also has a lot of studies to support its use. However, I'm pretty sure the evidence does not support that Haldol is better then the atypicals (or worse)...Or that any one atypical is better then the another. Although I'm not sure how many studes have been done with Abilify or Geodon. (Maybe Doc Samson can weigh in on this?) A lot of doc's don't like to use Olanzapine b/c it has the highest anticholinergic SE's of the atypicals. But, there are a lot of studies that support it works just as well as the others. Seroquel is a fine choice and a lot of psychiatrists like it b/c of the EPS issue as well as utilizing its sedating proprieties. It is also nice for someone with Parkinson's. For what it's worth, I like Risperdal...

In the end, it is probably better to look at the overall clinic picture and make your choice based on the patient and your needs. For example, do you need an IM b/c they're too agitated to take a PO med? Do you have a patient Parkison's?

Here is a good article: Delirium in the Acute Care Setting: Characteristics, Diagnosis, and Treatment by Jose R. Malodonado in Critical Care Clinics 24 (2008) 657-722

 

[MDchouette]

As a med student, it's acceptable and encouraged to ask your medicine residents and attendings why they use Seroquel. You can tell them you looked it up in the Wash Manual of Medical Therapeutics and it said (pg 9 of 31st edition) that Haldol is considered the first choice. Be sure that whatever you quote you did look up. To stroke egos and get a more useful response, tell them that you suspect the info in your books is based on old info and you're sure they are using more recent primary publications, so you'd like to know where to read more about their decision to use Seroquel, and that you hope you can even convince the stodgy psychiatrists to utilize this newer information.

Please let us know what you get.

I did ask and wasn't satisfied with the response, which is why I'm bringing my question here. The attending I am working with, prior to working at this hospital, used to use Haldol, but has since transitioned to Seroquel because "that's what all the other attendings were using." He admitted that this wasn't evidence-based at all. He's extremely friendly, and I think would respond well to whatever information I can bring him. The Washington Manual is a great suggestion.

 

[maranatha]

I think would respond well to whatever information I can bring him.

The Maldonado article I cited above is very comprehensive and recommends Haldol...But it is just as reasonable to use Risperdal or Seroquel, depending on your patient's needs.

 

[Doc Samson]

The Medicine and Psych services at my medical school differ in how they treat delirium -- Psych tends to use Haldol, while the IM docs use Seroquel. I am biased to trust the Psych docs, but I (a newly minted MS4) don't know the research on this. I'm wondering about the opinions of the psych docs and residents on this forum.

I think of delirium as an anticholinergic and dopaminergic phenomenon, so choosing Seroquel over Haldol doesn't make sense to me (other than to decrease the chance of EPS).

Is there an article that you all would recommend?

You're absolutely right - delirium is an syndrome of hypocholinergia and hyperdopaminergia, so Haldol is a great 1st line agent since it strongly blocks dopamine and has essentially no anticholinergicity. Seroquel is a reasonable 1st choice ONLY if the patient has PD or Lewy body dementia, since it doens't bind to the D2 receptor at all and has a fair amount of anticholinergic action. Furthermore, seroquel has greater per dose equivalent prolongation of the QTc and is far more sedating than Haldol (optimizing cognition is the goal of treating delirium). I believe that there are maybe 2 or 3 double-blind controlled trials all with fairly low numbers but indicating that Chlorpromazine, Risperdal and Zyprexa are as effective as treating delirium as Haldol, but only measuring time to resolution (and ultimately, time to resolution is a function of identifying and treating the underlying cause, not which neuroleptic you're using). No blinded controlled studies have thus far measured intensity of delirium and level of patient functioning before resolution (which would actually be a function of the neuroleptic itself). As I mentioned in another thread, there's also now evidence that the butyrophenones (Haldol and Droperidol) are neuroprotective in delirium via a unique interaction at the sigma receptor - a phenomenon not seen with any other class of neuroleptic. In my experience, if one (on-patent, expensive) drug is used at a particular institution instead of Haldol, it's because the drug rep for that medication at that hospital is particularly effective (I know that's why I spend a lot of time d/c-ing Geodon at my shop).

 

[Regnvejr]

You're absolutely right - delirium is an syndrome of hypocholinergia and hyperdopaminergia, so Haldol is a great 1st line agent since it strongly blocks dopamine and has essentially no anticholinergicity. Seroquel is a reasonable 1st choice ONLY if the patient has PD or Lewy body dementia, since it doens't bind to the D2 receptor at all and has a fair amount of anticholinergic action.

A problem I see with dementia is that seroquel tend to increase confusion more. I have therefore not been brave enough to use it since residency. I still use haldol throughout. In the rare cases where a patient with delirium has not done well with haldol, my backup has been thorazine. Works better in severe burn patients, f.ex. (at least according to my past attendings in residency. Laziness has ensured I have not checked since). But the CATIE trials really were not that kind to seroquel , I'm always having this nagging feeling that I could prolong and intensify the delirium.

But I generally try to stay away from playing anesthesiologist and sedating patients. I have seen several cases of "delirium" that turns out to be a UTI that nobody bothered to check out first. Then they get annoyed if you order a lab on their patient and even more when you, the psychiatrist finds a UTI in their patient.

.. As I mentioned in another thread, there's also now evidence that the butyrophenones (Haldol and Droperidol) are neuroprotective in delirium via a unique interaction at the sigma receptor - a phenomenon not seen with any other class of neuroleptic.

Dang, I got to read more. Makes sense. Back in residency, most places had stopped using droperidol due to "unfortunate" outcomes on QT intervals. We were slow to change, and our clinic actually got a letter from the pharmacy Medicaid oversight informing us that we were the hospital with the highest use of droperidol in the nation. Finally, that got attention and we stopped almost overnight. Was great stuff, though, the best crowd-control tool you can imagine.

In my experience, if one (on-patent, expensive) drug is used at a particular institution instead of Haldol, it's because the drug rep for that medication at that hospital is particularly effective (I know that's why I spend a lot of time d/c-ing Geodon at my shop).

Agreed. You can give haldol for months at the cost of a day or two of Geodon im. Never tried the Abilify im, just have not had a reason. Haldol works.

 

[whopper]

Seroquel's dosage needs to be upped over time. Patients in delirium needing an antipsychotic often need it on a PRN basis. Seroquel if given at the lower dosages will bind to histiminic receptors first before binding to dopamine receptors.

So if dosage guidelines are followed, it'll take a few days before it may start having true dopamine blockage. It may still sedate the person effectively, but do so due to antihistaminic reasons.

Samson is the expert in this area on the board. I'd go with his advice.

 

[maranatha]

You're absolutely right - delirium is an syndrome of hypocholinergia and hyperdopaminergia, so Haldol is a great 1st line agent since it strongly blocks dopamine and has essentially no anticholinergicity. Seroquel is a reasonable 1st choice ONLY if the patient has PD or Lewy body dementia, since it doens't bind to the D2 receptor at all and has a fair amount of anticholinergic action. Furthermore, seroquel has greater per dose equivalent prolongation of the QTc and is far more sedating than Haldol (optimizing cognition is the goal of treating delirium). I believe that there are maybe 2 or 3 double-blind controlled trials all with fairly low numbers but indicating that Chlorpromazine, Risperdal and Zyprexa are as effective as treating delirium as Haldol, but only measuring time to resolution (and ultimately, time to resolution is a function of identifying and treating the underlying cause, not which neuroleptic you're using). No blinded controlled studies have thus far measured intensity of delirium and level of patient functioning before resolution (which would actually be a function of the neuroleptic itself). As I mentioned in another thread, there's also now evidence that the butyrophenones (Haldol and Droperidol) are neuroprotective in delirium via a unique interaction at the sigma receptor - a phenomenon not seen with any other class of neuroleptic. In my experience, if one (on-patent, expensive) drug is used at a particular institution instead of Haldol, it's because the drug rep for that medication at that hospital is particularly effective (I know that's why I spend a lot of time d/c-ing Geodon at my shop).

Most of the attendings were I train tend to pick the atypicals (if they can take PO meds) over Haldol and I had to show them the Maldonado article to support my choice of Haldol. I started getting a bit of slack from some of my attendings. I eventually settled on picking Risperdal for most of my patients who could tolerate PO meds and using Haldol if the pt was too agitated and needed a multi-route. Typically the attendings would site EPS as the reason they would pick an atypical over Haldol, which I thought was reasonable. But I suprised to hear that people are using Geodon for delirium. I've started using Geodon IM, however, in the ED and have gotten good results--less sedation helps with the interview. Have I've been secretly brain washed by the drug reps???

there's also now evidence that the butyrophenones (Haldol and Droperidol) are neuroprotective in delirium via a unique interaction at the sigma receptor - a phenomenon not seen with any other class of neuroleptic.

That's pretty cool. Do you have an article to support this?

 

[Doc Samson]

Most of the attendings were I train tend to pick the atypicals (if they can take PO meds) over Haldol and I had to show them the Maldonado article to support my choice of Haldol. I started getting a bit of slack from some of my attendings. I eventually settled on picking Risperdal for most of my patients who could tolerate PO meds and using Haldol if the pt was too agitated and needed a multi-route. Typically the attendings would site EPS as the reason they would pick an atypical over Haldol, which I thought was reasonable. But I suprised to hear that people are using Geodon for delirium. I've started using Geodon IM, however, in the ED and have gotten good results--less sedation helps with the interview. Have I've been secretly brain washed by the drug reps???

there's also now evidence that the butyrophenones (Haldol and Droperidol) are neuroprotective in delirium via a unique interaction at the sigma receptor - a phenomenon not seen with any other class of neuroleptic.

That's pretty cool. Do you have an article to support this?

EPS with IV Haldol is almost unheard of. If I need to transition a patient to a PO med I typically pick Risperdal since oral Haldol really is quite toxic.

Refs for the sigma receptor stuff:

Schetz JA, Perez E, Liu R, et al: A prototypical Sigma-1 receptor antagonist protects against brain ischemia. Brain Res 2007; 1181:1–9

Lee IT, Chen S, Schetz JA: An unambiguous assay for the cloned human sigma-1 receptor reveals high affinity interactions with dopamine D4 receptor selective compounds and a distinct structure-affinity relationship for
butyrophenones. Eur J Pharmacol 2008; 578:123–136

 

[Hurricane]

EPS with IV Haldol is almost unheard of. If I need to transition a patient to a PO med I typically pick Risperdal since oral Haldol really is quite toxic.

Que?

Elaborate please

 

[Doc Samson]

Que?

Elaborate please

Oral Haldol is, as you know, very strongly associated with EPS. IV Haldol is not associated with EPS (I've never seen a dystonia or any other form of EPS from the IV formulation). This is thought to be due to avoiding the first-pass effect and minimizing accumulation of the toxic haldol metabolite (norhaloperidol, I think) primarily responsible for EPS.

 

[Hurricane]

Oral Haldol is, as you know, very strongly associated with EPS. IV Haldol is not associated with EPS (I've never seen a dystonia or any other form of EPS from the IV formulation). This is thought to be due to avoiding the first-pass effect and minimizing accumulation of the toxic haldol metabolite (norhaloperidol, I think) primarily responsible for EPS.

Thanks for the explanation. Is IV haldol associated with more cardiac effects? A lot of people won't do it unless the patient is on a monitor...

 

[Doc Samson]

Thanks for the explanation. Is IV haldol associated with more cardiac effects? A lot of people won't do it unless the patient is on a monitor...

See the other recent Haldol thread - ultimately, the answer is we don't know, but in my practice, the patient doesn't necessarily have to be on telemetry (anymore than they have to be on telemetry for levaquin or nifedapine).

 

[kugel]

Who's got a (relatively short) reading list for current treatment of delirium?
I'd like to update (maybe throw out) the folder I have from 10 years ago.

 

[maranatha]

Who's got a (relatively short) reading list for current treatment of delirium?
I'd like to update (maybe throw out) the folder I have from 10 years ago.

While not a reading list per se, I think the article I cited earlier is a very good review of the research on delirium and the recommendations seem very sound.

Delirium in the Acute Care Setting: Characteristics, Diagnosis, and Treatment by Jose R. Malodonado in Critical Care Clinics 24 (2008) 657-722

 

[whopper]

had to show them the Maldonado article to support my choice of Haldol. I started getting a bit of slack from some of my attendings.

Be careful in giving some attendings data that would go against their current mode of thinking.

The way medicine is, there's always advancements going on, and no one knows everything. There's too much data. Since the practice of medicine often times incorporates elements that are not reinforced outside of practice, several doctors forget data that is information they haven't practiced upon for months to years.

So for that reason, I try to keep an open mind whenever someone "under" me has a suggestion that may counter something I'm doing. Aside from that, I'm a new attending, and I figure I could always learn more.

However not all attendings are like this. Several doctors have big egos and a streak of narcissism. Several doctors figure out one med works and always give out that 1 med, even though its not the best med per evidenced based data.

And also factor that you may not be correct yourself. The doctor may have some reasoning you haven't figured out. Always be diplomatic in these situations.

 

[maranatha]

Be careful in giving some attendings data that would go against their current mode of thinking.

The way medicine is, there's always advancements going on, and no one knows everything. There's too much data. Since the practice of medicine often times incorporates elements that are not reinforced outside of practice, several doctors forget data that is information they haven't practiced upon for months to years.

So for that reason, I try to keep an open mind whenever someone "under" me has a suggestion that may counter something I'm doing. Aside from that, I'm a new attending, and I figure I could always learn more.

However not all attendings are like this. Several doctors have big egos and a streak of narcissism. Several doctors figure out one med works and always give out that 1 med, even though its not the best med per evidenced based data.

And also factor that you may not be correct yourself. The doctor may have some reasoning you haven't figured out. Always be diplomatic in these situations.

Yeah, that is great advice and something I need to keep in mind. It is difficult, though, when an attending makes recommendations that is not supported by the data.