What do you think of these studies using the intensivist's best friend, aka Precedex, in PO form for agitation in Schizophrenia and Bipolar disorder? I'd wonder if this would have applications in hyperactive delirium and/or dementia with behavioral disturbance. Brand name POPrecedex is my suggestion.
dexmedetomidine (POPrecedex) for agitation, and maybe delirium, and maybe dementia with behavioral disturbance?
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What do you think of these studies using the intensivist's best friend, aka Precedex, in PO form for agitation in Schizophrenia and Bipolar disorder? I'd wonder if this would have applications in hyperactive delirium and/or dementia with behavioral disturbance. Brand name POPrecedex is my suggestion.
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Commonly used sedative can be sedating. Stop the presses!
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Yeah I mean I think the biggest deal here is getting some kind of PO form of precedex at all. That was always the biggest issue with precedex that you only had the IV route and it basically had to be a drip, otherwise it’s a great sedative agent because there’s no risk of respiratory depression.
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This PO version will probably turn out to be a popular option in the future to treat acute agitation in delirium. Not sure how useful this medication will be in people with schizophrenia or bipolar. If they are willing to take a PO med, why not just give them something that will help with the underlying psychosis or mania that is driving the agitation. It doesn’t work much faster than existing options either. Seems to take 20 minutes at least and it will likely have a short duration of action.
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Why not both? Agitation is a common symptom in bipolar d/o and schizophrenia and often more than one med is prescribed. Instead of Ativan or Benadryl, maybe it could be dex?
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Does Your Dog Overreact to Everyday Noises?
SILEO® (dexmedetomidine oromucosal gel) is the first FDA-approved treatment for dogs that suffer from a serious condition called noise aversion.
www.zoetispetcare.com
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It would have to be safer, cheaper, and more effective than Ativan. Considering how safe, cheap, and effective Ativan is for acute agitation, that will be a while.
Same thing with adding a 5-20 mg dose of Zydis or whatever their primary med is. Super safe, effective, well tolerated, logical, and cheap.
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Well I didn't say it would or should be available for that tomorrow. I was responding to this "Not sure how useful this medication will be in people with schizophrenia or bipolar. If they are willing to take a PO med, why not just give them something that will help with the underlying psychosis or mania that is driving the agitation."
I'm saying it's not an either/or. There's no reason you can't prescribe the med to treat their underlying psychosis or mania AND add dex as an adjunct prn just as we do now once dex is more widely available and affordable.
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It will have to depend on the side effect profile with repeated administration or in combination with other drugs, given precedex's likely short duration of action. It's not clear from the article if the SERENITY I and II trials tested precedex in multiple administrations or just one administration. Precedex seems to cause much larger changes in BP and heart rate than benzos and antipsychotics.
Given the high cost of the PO precedex, I can't see it replacing benzos in the psychiatric population because its onset of action is not much faster and the duration of action will likely be shorter. Of course, the pharmaceutical company may run a really effective advertising campaign and convince everyone to use it, who knows.
In delirium, PO precedex can have a role because it is not delirogenic and won't prolong the QT interval.
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Does Your Dog Overreact to Everyday Noises?
SILEO® (dexmedetomidine oromucosal gel) is the first FDA-approved treatment for dogs that suffer from a serious condition called noise aversion.
I thought this was a gag website at first....
Maybe they'll get an approval for autism.
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Not at all, I use it on my golden whenever there are fireworks. Works great.
The question for dexmedetomidine is why use it over another alpha-2 agonist? Prima facia it doesn't seem to have much advantage.
Dexmedetomidine: DOA 1-2 hours, hemodynamically active
Tizanidine: DOA 4 hours, not particularly hemodynamically active
Clonidine: DOA 8 hours (ER 12 hours, Patch 7 days), significantly effects on hemodynamic
Guanfacine: DOA 12 hours (ER 24 hours), relatively less hemodynamic activity
Dexmedetomidine: DOA 1-2 hours, hemodynamically active
Tizanidine: DOA 4 hours, not particularly hemodynamically active
Clonidine: DOA 8 hours (ER 12 hours, Patch 7 days), significantly effects on hemodynamic
Guanfacine: DOA 12 hours (ER 24 hours), relatively less hemodynamic activity
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The other 3 medications don't work for acute agitation due to differences in onset of action and specificity for a2. Of these 4 drugs, precedex is the most selective for a2 and has the fastest onset of action. Guanfacine is more selective than clonidine. Not sure where tizanidine falls.
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Just FYI guanfacine IR's DOA is much less than 12 hours despite it's half-life. There are some good pubmed articles on this (it's a big part of CAP these days so if you are adult psychiatrist I imagine you may not have read this literature). BID dosing is usually insufficient although this point is generally immaterial for ADHD management these days as guanfacine ER is generic and on every formulary I've seen.
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I am very interested to see if this medication can be used safely in children. Lots of advantage to alpha agonists versus BZDs and antipsychotics in the pediatric age range and we already heavily use guanfacine and clonidine. We badly need PRNs that can be used both on inpatient units but also for children with ID/ASD living in the community. I really hope this quickly gets translational research to kids and doesn't take decades for someone to be brave enough to use it in this population.
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I just really don't see a place to add Precedex, and the studies don't seem to be looking for it in combination to assess safety and tolerability. There's just so many cheap, safe, and effective options for PO meds for bipolar disorder or schizophrenia, and most of these would be reasonable for single dosing for severe agitation in dementia (at lower doses). Just off the top of my head in no particular order and interventions that I use not infrequently:
Haldol 5-10 alone
Haldol 5-10 + Ativan 1-2
Haldol 5-10 + Ativan 1-2 + Benadryl 25-150
Ativan 1-4 alone
Ativan 1-2 + Benadryl 25-150
Zydis 5-20
Zydis 5-20 + Ativan 1-2
Thorazine 25-200 alone
Thorazine 25-200 + Ativan 1-2
Loxapine 10-50
Loxapine 10-50 + Ativan 1-2
Seroquel 25-100 alone
Seroquel 25-10 + Ativan 1-2
Prolixin 5-10 alone
Prolixin 5-10 + Ativan 1-2
Prolixin 5-10 + Ativan 1-2 + Benadryl 25-150
addition of 0.5-2x the current scheduled daily dose of antipsychotic
Where would adding PO Precedex fit into this? Do we know the safety profile of it in combination with any of these? People frequently harp on the combination of IM Zyprexa and Ativan, but do they remember that Haldol/Ativan/Benadryl actually has a more substantial effect on dropping blood pressure than Zyprexa/Ativan? What will happen when we see that PO Precedex does have an effect on BP, especially when combined with any of these agents?
I imagine PO Precedex combinations will be like the Zyprexa/Ativan combo, where despite nobody ever actually dying BECAUSE of the combination, nursing committees, pharmacists, and the like will make a blanket ban on ever considering the combination and forcing psychiatrists to instead substitute to a more dangerous combination. It doesn't help Precedex's case that it's currently used (in humans) exclusively in ICUs. That's where the alleged problems with Zyprexa/Ativan came up to begin with.
Or it will end up like inhaled loxapine, where a REMS will limit it to never being used at all.
Haldol 5-10 alone
Haldol 5-10 + Ativan 1-2
Haldol 5-10 + Ativan 1-2 + Benadryl 25-150
Ativan 1-4 alone
Ativan 1-2 + Benadryl 25-150
Zydis 5-20
Zydis 5-20 + Ativan 1-2
Thorazine 25-200 alone
Thorazine 25-200 + Ativan 1-2
Loxapine 10-50
Loxapine 10-50 + Ativan 1-2
Seroquel 25-100 alone
Seroquel 25-10 + Ativan 1-2
Prolixin 5-10 alone
Prolixin 5-10 + Ativan 1-2
Prolixin 5-10 + Ativan 1-2 + Benadryl 25-150
addition of 0.5-2x the current scheduled daily dose of antipsychotic
Where would adding PO Precedex fit into this? Do we know the safety profile of it in combination with any of these? People frequently harp on the combination of IM Zyprexa and Ativan, but do they remember that Haldol/Ativan/Benadryl actually has a more substantial effect on dropping blood pressure than Zyprexa/Ativan? What will happen when we see that PO Precedex does have an effect on BP, especially when combined with any of these agents?
I imagine PO Precedex combinations will be like the Zyprexa/Ativan combo, where despite nobody ever actually dying BECAUSE of the combination, nursing committees, pharmacists, and the like will make a blanket ban on ever considering the combination and forcing psychiatrists to instead substitute to a more dangerous combination. It doesn't help Precedex's case that it's currently used (in humans) exclusively in ICUs. That's where the alleged problems with Zyprexa/Ativan came up to begin with.
Or it will end up like inhaled loxapine, where a REMS will limit it to never being used at all.
One other thing to consider with dex (and the other alpha-2s) is that a lot of antipsychotics are alpha-1 antagonists, so blood pressure becomes a significant concern.
My thought is that dex PO will have a role but until the patent runs out marginal benefit <<<<marginal cost
