question about quetiapine

[Hurricane]

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I've heard people say that at low doses, quetipaine is essentially benadryl. What exactly do y'all mean by "low dose"? And at what dose do you have to start worrying about prolonged QTc?

 

[whopper]

Seroquel, like pretty much any medication has multiple effects on multiple receptors.

Its strongest effect is as an antihistamine.

You only start seeing the antipsychotic benefits at doses much higher than 200mg, which is where the antihistamine effect tops out.

It also has alpha agonism, D2 blockage, serotonin receptor interaction in addition to other effects.

I don't know exactly at what dosage you see QTC prolongation. The first time I've noticed this occuring was with the CATIE trials, but as far as I know, the trials didn't state where you start seeing it. The trials though did specify what doses Seroquel was given out, so at least you have some benchmark to work with.

You have to give the right med for the right reason but in general, Seroquel is my least favorite atypical antipsychotic, though in specific conditions I'll give it out.

 

[Solideliquid]

When I see people come in on Seroquel 50mg QHS I'm like what? So that's probably what they mean by low dose. I really don't see the point, this is an expensive medicine, afterall.

Not to hijack your thread, but I was wondering if the more experienced folks can chime in with their favorite sleep agent? What would you give to someone you are seeing as an outpatient who complains of insomnia?

 

[whopper]

I think stating which is the favorite sleep med is moot.

Any doctor worth his/her salt knows that sleep problems need specific meds for specific conditions. E.g. give a longer t1/2 med if the patient frequently wakes up during the night. Give a shorter t/2 med if the patient's problem is more on just falling asleep. Give melatonin or rozarem if the sleep problem is light and more based on a circadian rhythm problem.

I will though state that all docs should avoid xanax to sleep. Its highly addictive and ativan (which is addictive but less so) works just as well in studies, so why give xanax at all? Heck, if you ask me, pretty much any benzo should be avoided in sleep disorders.

I am also upset with the idiot docs that give out Seroquel so liberally to replace benadryl. Benadryl costs $10 a month for use, and Seroquel costs hundreds. Any doc giving out seroquel just for sleep is wasting the system money. Kinda like the idiots who prescribe prozac which is over $100 a month when the pt just could've gotten fluoxetine for $20.

One of the reasons why kids with cancer can't pay for medical bills.

 

[Solideliquid]

I think stating which is the favorite sleep med is moot.

Any doctor worth his/her salt knows that sleep problems need specific meds for specific conditions. E.g. give a longer t1/2 med if the patient frequently wakes up during the night. Give a shorter t/2 med if the patient's problem is more on just falling asleep. Give melatonin or rozarem if the sleep problem is light and more based on a circadian rhythm problem.

I will though state that all docs should avoid xanax to sleep. Its highly addictive and ativan (which is addictive but less so) works just as well in studies, so why give xanax at all? Heck, if you ask me, pretty much any benzo should be avoided in sleep disorders.

I am also upset with the idiot docs that give out Seroquel so liberally to replace benadryl. Benadryl costs $10 a month for use, and Seroquel costs hundreds. Any doc giving out seroquel just for sleep is wasting the system money. Kinda like the idiots who prescribe prozac which is over $100 a month when the pt just could've gotten fluoxetine for $20.

One of the reasons why kids with cancer can't pay for medical bills.

There really isn't a need for name calling, we don't know the entire story do we? I mean isn't it possible in some cases that patients refuse something like benadryl? I know many of my patients on the inpatient unit frequently ask for a sleep aid but don't want benadryl as they have tried it and they say it doesn't work for them. Given some of these are seeking benzos, on the other hand we have had a few lectures by our attendings about using benzos as sleep aids. Our attendings say benzos can be very helpful in insomnia (though insomnia is a secondary dx and we should treat the primary problem) as long as you trust the patient and give limited quantities.

 

[50960]

Benzos will put people to sleep, bvut being as they interfere with deep, restorative (s-4) sleep you will eventually make the problem worse if they are use for more than a few days. That is why ambien and lunesta are good because they have minimal if any effect on stage 4 sleep, but knock people out like a benzo. Quetiapine is much more effective than benadryl, and is often the best bet especially with pts who have a hx of taking benzos etc.

 

[watto]

I know that pharmacotherapy is implied by "sleep agent," but don't forget CBT!

Arch Intern Med. 2004 Sep 27;164(17):1888-96.
Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison.
Jacobs GD, Pace-Schott EF, Stickgold R, Otto MW.
Sleep Disorders Center, Beth Israel Deaconess Medical Center, Laboratory of Neurophysiology, Harvard Medical School, Boston, MA 02215, USA. [email protected]

BACKGROUND: Chronic sleep-onset insomnia is a prevalent health complaint in adults. Although behavioral and pharmacological therapies have been shown to be effective for insomnia, no placebo-controlled trials have evaluated their separate and combined effects for sleep-onset insomnia. The objective of this study was to evaluate the clinical efficacy of behavioral and pharmacological therapy, singly and in combination, for chronic sleep-onset insomnia. METHODS: This was a randomized, placebo-controlled clinical trial that involved 63 young and middle-aged adults with chronic sleep-onset insomnia. Interventions included cognitive behavior therapy (CBT), pharmacotherapy, or combination therapy compared with placebo. The main outcome measures were sleep-onset latency as measured by sleep diaries; secondary measures included sleep diary measures of sleep efficiency and total sleep time, objective measures of sleep variables (Nightcap sleep monitor recorder), and measures of daytime functioning. RESULTS: In most measures, CBT was the most sleep effective intervention; it produced the greatest changes in sleep-onset latency and sleep efficiency, yielded the largest number of normal sleepers after treatment, and maintained therapeutic gains at long-term follow-up. The combined treatment provided no advantage over CBT alone, whereas pharmacotherapy produced only moderate improvements during drug administration and returned measures toward baseline after drug use discontinuation.
CONCLUSIONS: These findings suggest that young and middle-age patients with sleep-onset insomnia can derive significantly greater benefit from CBT than pharmacotherapy and that CBT should be considered a first-line intervention for chronic insomnia. Increased recognition of the efficacy of CBT and more widespread recommendations for its use could improve the quality of life of a large numbers of patients with insomnia.

 

[Hurricane]

Seroquel, like pretty much any medication has multiple effects on multiple receptors.

Its strongest effect is as an antihistamine.

You only start seeing the antipsychotic benefits at doses much higher than 200mg, which is where the antihistamine effect tops out.

It also has alpha agonism, D2 blockage, serotonin receptor interaction in addition to other effects.

So at lower doses (like < 200) it has a lot of binding at the H1 receptor, but negligible at the others? I looked in Stahl expecting to find a dose-response for the different receptors but came up nada.

Quetiapine is much more effective than benadryl, and is often the best bet especially with pts who have a hx of taking benzos etc.

Why is it more effective if the sedative effects of both work via the same mechanism?

I found this article which looks pertinent: Sleep-promoting properties of quetiapine in healthy subjects
But I haven't yet figured out how to access journals at my new institution and my old med school locked me out 🙁

I know that pharmacotherapy is implied by "sleep agent," but don't forget CBT!

Interesting. Not to knock CBT, but I wonder what would have been the results if they compared CBT to simple instructions on good sleep hygiene... No caffeine after 3, only use the bed for sleeping, etc.

 

[OldPsychDoc]

I know that pharmacotherapy is implied by "sleep agent," but don't forget CBT!
....
CONCLUSIONS: These findings suggest that young and middle-age patients with sleep-onset insomnia can derive significantly greater benefit from CBT than pharmacotherapy and that CBT should be considered a first-line intervention for chronic insomnia. Increased recognition of the efficacy of CBT and more widespread recommendations for its use could improve the quality of life of a large numbers of patients with insomnia.

This is fine, and seriously, we don't push behavioral interventions hard enough, but it should really be pointed out that the subjects of this study were, well, normal--i.e. not psychiatric patients. Treating insomnia in the depressed, severely anxious, psychotic, or withdrawing patient is a different task entirely. That's why I have yet to prescribe Rozerem (indicated for "primary insomnia"), and why, frankly, I use a boatload of Seroquel in my patients.

 

[Anasazi23]

CBT is psychiatric inpatient is a great idea. It's also completely impractical and unrealistic.

Seroquel "low dose" generally refers to 200mg or less. Since dosages above this act on different receptors to some degree in some patients.

Benadryl and Seroquel will both help you sleep. However, benadryl is more likely to produce a tachyphylactic effect after a short period, cause vivid dreams and nightmares, and possibly other undesirable effects. Seroquel appears to produce this less often. Though I hate medical 'waste' as much as anybody, if not more, so I take your point to heart.

 

[whopper]

Apologize and don't apologize for the "name calling".

Apologize if it offended you, but I don't apologize to the docs that really are just too lazy to take the 30 seconds to check out the costs.

Again, why prescribe prozac when fluoxetine's out and at a fraction of the cost? Why give out Seroquel if what you want is simply the antihistamine effect? You're giving out $300 benadryl or vistaril if you do that. Yeah, I know Seroquel does more than an antihistamine, but a lot of docs just give it out to act as a $300 antihistamine, thanks to the drug reps from Astra Zeneca.

I don't know if its going on where you are, but its going on where I am. This is similar to those patients who come to the hospital due to noncompliance because they couldn't pay for their meds, and the doctor just gives them prozac again (again, over $100) when they just could've given fluoxetine & solved the problem.

Its just pure laziness. I know it because I'm working with these people, or get their patients. Those are the people I'm judging, not every doctor in the US most of whom I haven't met and not you. I should've clarified that in my previous post.

 

[DeanWormer]

Ambien is not a benzo but very much works off the same mechaism intracellularly. I see many people "seeking" Ambien as they did Halcion in the past. I'd avoid Ambien in your chemically dependent population.

 

[OldPsychDoc]

Ambien is not a benzo but very much works off the same mechaism intracellularly. I see many people "seeking" Ambien as they did Halcion in the past. I'd avoid Ambien in your chemically dependent population.

Chemically not a benzo, but if you hit 20 mg (which many patients do, d/t tolerance effects) it is basically indistiguishable physiologically from a benzo. Therefore, might as well treat it like a benzo!

 

[Anasazi23]

I don't know if its going on where you are, but its going on where I am. This is similar to those patients who come to the hospital due to noncompliance because they couldn't pay for their meds, and the doctor just gives them prozac again (again, over $100) when they just could've given fluoxetine & solved the problem.

I'm not sure what state you're in, or if it's different to any degree, but my understanding was that a pharmacist could replace a brand for a generic with the patient's acknowledgement, and as long as the doctor didn't DAW on the prescription.

 

[Solideliquid]

Daw?

 

[50960]

I think he meant draw... Sazi like to draw little, cute pics on his Rx's..LOL

 

[OldPsychDoc]

Daw?

Dispense As Written, i.e.--no generic substitution, please.

 

[bridge2006]

This is fine, and seriously, we don't push behavioral interventions hard enough, but it should really be pointed out that the subjects of this study were, well, normal--i.e. not psychiatric patients. Treating insomnia in the depressed, severely anxious, psychotic, or withdrawing patient is a different task entirely.

Can't remember the citation for the article, but while I was on my inpatient rotation I read up about CBT for insomnia and found an article that looked at using the technique on real psych patients. It apparently worked quite well, though I was not able to replicate its success with my patients.

In response to an earlier post about sleep hygiene: sleep hygiene (along with relaxation techniques) are the "B" component of CBT for insomnia.

Cheers!

 

[sdn1977]

I'm not sure what state you're in, or if it's different to any degree, but my understanding was that a pharmacist could replace a brand for a generic with the patient's acknowledgement, and as long as the doctor didn't DAW on the prescription.

We not only can, but we are obligated to do so. DAW (dispense as written) can be up to multiples of 8 different types. The most common are DAW-1 (no substitution per physician), DAW-2 (no substitution per patient) - these usually result in different insurance reimbursement rate. The other common is DAW-3 (brand dispensed as generic - usually due to manufacturer issues which allow the insurance to pay as a generic, but we dispense brand).

On a practical note....altho Seroquel is a brand & is expensive, when compared to Benadryl...pts complain less of dry mouth & daytime sluggishness with low hypnotic Seroquel doses than Benadryl which they sometimes ramp up to 50mg. Also...only Medicaid pays for Benadryl & only for certain conditions, otherwise, it is out of pocket. Insurance pays for Seroquel in nearly all situations.

Its true - diphenhydramine is inexpensive, but there is a whole psychological (I feel like an idiot bringing up that term in this forum😳 ) factor in taking a prescription medication - studies show the exact same medication will work "better" if it is dispensed like an rx than if purchased otc. They also have to overcome the marketing on the box.....if you go look at the boxes on the shelves...the very same diphenhydramine will be marketed in different packages for rash or hay fever. Its hard to convince someone to take something for a purpose which is not listed. You & I know it, but they don't.

Same phenomenon occurs with otc Prilosec & Claritin...suddenly they didn't work as well when the pt pays out of pocket. Sales of other ppis & h1 blockers go up.

 

[whopper]

True SDN

But then why not try an $10 antihistamine first before you pull out the $300 guns?

Yes insurance can pay for seroquel, but remember, there's usually a copayment, which is usually more expensive than $10, and you're still raising the health costs of everyone else. A doctor should try to do what he/she can for the patient, but also if possible the community.

I haven't read the studies you refered to on Rx vs OTC effects but still sounds like a poor reason to give a much more expensive med--because of the placebo effect. If a drug rep were to advocate that type of practice, it would be slammed as possible fraud. We aren't drug reps but we should not engange in ethically questionable behavior.

"my understanding was that a pharmacist could replace a brand for a generic with the patient's acknowledgement, and as long as the doctor didn't DAW on the prescription."

Yes, works here in NJ also, but some pharamacists won't replace for the generic. If you just prescribe fluoxetine, you eliminate that possibility. But to give another example, we get patients who get depressed due to noncompliance because they can't afford the med, and then are put on an even more expensive med by the inpatient doctor covering the case, whether its prozac/fluoxetine or not.

 

[sdn1977]

True SDN

But then why not try an $10 antihistamine first before you pull out the $300 guns?

Yes insurance can pay for seroquel, but remember, there's usually a copayment, which is usually more expensive than $10, and you're still raising the health costs of everyone else. A doctor should try to do what he/she can for the patient, but also if possible the community.

I haven't read the studies you refered to on Rx vs OTC effects but still sounds like a poor reason to give a much more expensive med--because of the placebo effect. If a drug rep were to advocate that type of practice, it would be slammed as possible fraud. We aren't drug reps but we should not engange in ethically questionable behavior.

"my understanding was that a pharmacist could replace a brand for a generic with the patient's acknowledgement, and as long as the doctor didn't DAW on the prescription."

Yes, works here in NJ also, but some pharamacists won't replace for the generic. If you just prescribe fluoxetine, you eliminate that possibility. But to give another example, we get patients who get depressed due to noncompliance because they can't afford the med, and then are put on an even more expensive med by the inpatient doctor covering the case, whether its prozac/fluoxetine or not.

Whopper - I agree with you - no reason at all to pay so much for the side effect you are looking for which can be satisfied by a less expensive drug.

However....my own experience - which is certainly far, far less than all of yours when seeing pts being tx for psych conditiions, but I might venture to say might be equal if not greater than all of yours since many folks do indeed try a variety of otc antihistamines & will utilize my free advice for sleep disorders before seeking out a physician...is that the side effects, particularly if used for greater than 7 days, of diphenhydramine limits its use. But...it works great if the insomnia is of limited duration & they don't foul up their sleep cycles too much with the anthistamine.

As for the studies...you wouldn't see them since they are compliance studies which are reported in my literature. You'd have to look in my literature since it looks at not just psych, but all rx medications. It is a continuing problem for us when a physician writes for an otc & the pt brushes it off. This is not limited to your area of practice - it occurs with pyridoxine when INH is prescribed, folic acid for a variety of conditions, omeprazole & the many other rx meds which went otc. There is a mentality that they went to see you & they want an rx - not something they could have picked up without paying your fee. It may not make any sense to you or I, but its there nonetheless. Compliance is a HUGE issue in my business & there are a whole lot of reasons, pt acceptance, the medication meeting their expectations & the cost are only a few. Your patient population, I would have to say, is one of the most difficult to adhere to their regimens. I think I've said here before that what you're told by the pt he/she takes & what my fill records indicate can be very different! Medical problems from noncompliance with your advice, IMO, is more expensive than the medications themselves....but - thats just my observation - not fact.

As for NJ....I can't comment on their laws - I have no knowledge of them. In CA, I'm OBLIGATED to provide a generic - it is not my choice. When there is a generic, I must give the pt the choice & adhere to what their choice is unless you, as a prescriber, have otherwise indicated. But, I do know some states don't allow for changing dosage forms, which in CA we do as long as they are therapeutically equivalent. So....if you wrote for Prozac tablets,which have no generic....I can change to fluoxetine capsules. But - that may not be possible in NJ.

 

[whopper]

Good thoughtful answer, one of the reasons why I like this board. We discuss psychiatry for real.

I got no problem with difference of opinion, just don't like it when someone does something stupid out of laziness when it comes to a patient's health.

Thanks for your time. Trust me I don't want to beat this dead horse.

 

[scottj00]

3rd year on psych rotation now. I believe that longer term use of diphenhydramine causes unwanted changes to sleep architecture whereas quetiapine does not.

 

[Doc Samson]

Given my population of elderly and medically ill patients, benadryl is definitely not the same as Seroquel. If I ordered benadryl, I might as well write "Agitated delirium, nightly, repeat until mechanical restraints are required" due to the anticholinergic load. Sure Seroquel has some anticholinergicity, but it also comes with (at least some) dopmaine blockade to offset it. Like OPD, I write a for a ton of Seroquel as a sleeper and as an anxiolytic.

 

[OldPsychDoc]

...I might as well write "Agitated delirium, nightly, repeat until mechanical restraints are required" ....

Now that sounds like a fun order to write!

 

[worriedwell]

Thats why in vivo and in vitro seem to produce different results (or at least we interpret our clinical findings in ways that contradict the pure research in vitro). Because if you read the data, based on receptor affinity, there is supposed to be zero dopamine blockade at low doses of seroquel (ie the doses where we use it as a sleeper). But every psychiatrist in clinical practice is in love with seroquel for sleep, borderlines, anxiety patients, etc etc mixed in with some people who actually have psychosis. Throw in the new FDA indication for bipolar depression and it is basically something we should start putting in the water for everybody. It is the lipitor of psychiatry. The current single most prescribed antipsychotic and I for some reason I remember reading it is the most prescribed psychiatric drug in the US (don't quote me on this, I'm not in the mood to look it up at this moment).

best,
worriedwell

 

[Doc Samson]

Based on receptor affinity, there's no dopamine blockade at any dose of Seroquel (or Clozaril for that matter), thus raising the concept of dopamine blockade via induced conformational change of the receptor.