Megadoses of Seroquel (1500 mg to 2400 mg daily)

[NewtonLeibniz]

There is a famous psychiatrist who had a daily radio show in the 1990s and 2000s who went to war with his professional order on various fronts.This psychiatrist had a habit of making controversial statements and it was apparent that his professional order didn't appreciate him representing their profession in public, so they started trying to suspend him over many things.Moreover, he was a rural, farmer type of guy, and the language sometimes followed (don't get me wrong he was gifted with language, but he did use rural slurs every now and then).There was certainly an impression that he kept telling inconvenient truth about widespread family dynamics and increasingly many people were uncomfortable with that.He was a no-nonsense kind of guy; you get the picture.

(I'm just going by memory here)

He was known as a psychiatrist who saw a lot of the most severe cases of schizophrenia.He was accused of prescribing doses of seroquel of 1500 mg daily, and even 2400 mg daily to some patient.He didn't hide it, on the contrary, he claimed and still claims he is an expert on treatment for severe schizophrenia and that he's innovating.

Paradoxally, he claims he's among the psychiatrists who prescribes the least SSRIs and benzos to people who come to him depressed and anxious, preferring to talk and get to the root of the problem (in general).

The legal battle started around 2001, and he got suspended many times but ultimately survived.He defended himself alone without lawyer for all those years (the battle lasted almost two decades).He is still on air and still practicing today.He is getting old now, 70 years old.Did his residency in McGill in the 1970s I presume.

Another of the countless things he advocated for was the voluntary surgical castration of severe cases of pedophilia.I think he did four, but complained that since his professional order stayed silent on this issue, the surgeons did it one time and stopped thereafter, since it was a gray area and they didn't want trouble.He even wrote a book pushing for this.

During one of his various suspensions, a group of his patients independently organized a protest on the street in a cold winter day, protesting his radiation since they appreciated him.On air, he was the kind of guy who had a natural talent for gaining people's trust quickly, and he leaned on the psychoanalytical side of things.

What do you guys make of such mega dosages for severe cases of schizophrenia? What about voluntary surgical castration of severe cases of pedophilia? Just trying to get a feel of what other psychiatrists thought.FTR, the actual facts are easy to find on google, though most likely in french.

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[birchswing]

voluntary

I'm surprised how often I see posts on Reddit in their askdocs forum with males wanting to find a way to get castrated.

What is the purpose if a person can take androgen-blocking drugs, which I'm assuming they'd be willing to if they're willing to undergo such a personal surgery? That's why I highlighted the word voluntary: Is there an implied threat such as in the case of voluntary admission vs involuntary admission?

 

[NewtonLeibniz]

I'm surprised how often I see posts on Reddit in their askdocs forum with males wanting to find a way to get castrated.

What is the purpose if a person can take androgen-blocking drugs, which I'm assuming they'd be willing to if they're willing to undergo such a personal surgery? That's why I highlighted the word voluntary: Is there an implied threat such as in the case of voluntary admission vs involuntary admission?

I will stick to the story of the psychiatrist.He had patients who had severe pedophilia, and committed crimes of that nature (one was a pyroman pedophile who killed 22 people with the fire he was starting and had been asking to get castrated for 7 years), and who wanted to have surgery.As far as I know the psychiatrist never pushed for involuntary surgical castration, only for voluntary.

 

[nexus73]

I'm surprised how often I see posts on Reddit in their askdocs forum with males wanting to find a way to get castrated.

What is the purpose if a person can take androgen-blocking drugs, which I'm assuming they'd be willing to if they're willing to undergo such a personal surgery? That's why I highlighted the word voluntary: Is there an implied threat such as in the case of voluntary admission vs involuntary admission?

It’s harder to reverse a castration than it is to stop taking a pill. If you don’t trust yourself then castration may be the way to go...if the alternative is you’ll be raping children.

 

[Crayola227]

yeah gonna weigh in and say that androgen blocking is not the equivalent of surgical castration by any means

the more I've explored of the BDSM underworld, the more of these sorts of fantasies I've been exposed to (amputation, emasculation, transgender, forced feminization, chastity, castration of all sorts, more controversial ageplay, etc)

correct me if I'm wrong, as I understood it there was evidence that androgen blocking/estrogen use was associated with a decrease of violence in male prison inmates etc

and that conversely, chemical/actual castration was NOT associated with a decrease in fantasizing or recidivism for paedophilia or sexual assault

my understanding is that this observation is partly why many take the view that these paraphilias are not about sex or just violent aggression, per se (power?)

one thing I read was that offenders who had been surgically or chemically castrated then just resorted to using objects to penetrate their victims, which often led to more serious injuries, not less

my understanding was that this observation re: sexual violence/paedophilia is precisely why there is no real good support for doing surgical castration, and that voluntary chemical castration is sort of take it or leave it as well

basically, you can take the dick/T out of the paedophile, but you can't take the paedophilia out of the paedophile

sexual desire is extremely complex, it's about more than genitals or hormones, which is why we don't always see the results we expect to see, and why voluntary chemical castration is not equivalent to surgical castration, and neither are "cures" for certain paraphilias

not getting into what happens with pubertal development, there is of course the observation that sexual desire can remain no matter what condition things are in downstairs or hormones/drugs (menopause, castration, "female circumcision," low T, SSRIs, you name it)

we observe issues with sexual desire as a result of biology all the time, so we sort of take for granted that even in one's deepest depression on SSRIs, just the lack of desire can be distressing, implying there is actually a desire for desire!! That even quadriplegics and 80 yr old with all their junk removed have interest in sex as well.

 

[Crayola227]

not to spoiler you all, but I legit cried a tear during that one super popular show that has a lot of castrated people, where this one guy castrated from early on in life, falls in love and discovers their sexuality

it's sorta this grey area where people have felt marginalized or unable to engage romantically or sexually because of physical limitations, and it's like hey, you don't have to have a dick to feel desire or to have a sex life

......which is unfortunately true for sexual predators as well

 

[J ROD]

I have seen folks use Seroquel 1200 daily before. Personally, I do not think you would get extra dopamine blockage etc worth the risks of increased side effects. Those patients that were on 1200 did not get better per se. Just running it up there. The other stuff is too far out there for me.

 

[splik]

I don't really prescribe seroquel, but people who actually use it to treat psychotic patients will tell you that you need to use high doses (i.e. 1000mg) and there are some small studies up to 1400mg. with refractory patients, it could be higher doses like the above could be indicated, especially if lack of efficacy or tolerability of other drugs. it's not unheard of for refractory patients to get 80mg of zyprexa. in the 80s, patients used to receive really high doses of neuroleptics, and in the 70s 120mg of haldol was considered standard. in hospitalized patients it is not unheard of for patients with delirium to receive thousands of mg of thorazine or haldol. It should not be routine for patients to get high doses of seroquel, but there is definitely a case to be made that in certain circumstances it could be appropriate.

in the US, voluntary surgical castration for pedophilia is considered unethical, because the "voluntariness" of the procedure is called into question. there are certainly urologists who would be interested in doing this, and there are sexually violent predators with pedophilia who would prefer surgical castration over chemical castration (i've come across these case) but in practice they are receiving their shots of Lupron. as an aside, few psychiatrists are trained in the management of paraphilias and sex offenders, and few psychiatrists prescribe chemical castration so it is probably under utilized. it should be provided as part of a comprehensive treatment program including behavioral/psychological treatments and monitoring including structrured risk assessment measures, and possibly penile plethysmography. as an aside, in canada pedophiles are shown provocative images of children during such testing, but this is not allowed in the US so they just show them regular images of clothed children with audio sounds that are sexually charged.

 

[AD04]

I don't really prescribe seroquel, but people who actually use it to treat psychotic patients will tell you that you need to use high doses (i.e. 1000mg) and there are some small studies up to 1400mg. with refractory patients, it could be higher doses like the above could be indicated, especially if lack of efficacy or tolerability of other drugs. it's not unheard of for refractory patients to get 80mg of zyprexa. in the 80s, patients used to receive really high doses of neuroleptics, and in the 70s 120mg of haldol was considered standard. in hospitalized patients it is not unheard of for patients with delirium to receive thousands of mg of thorazine or haldol. It should not be routine for patients to get high doses of seroquel, but there is definitely a case to be made that in certain circumstances it could be appropriate.

in the US, voluntary surgical castration for pedophilia is considered unethical, because the "voluntariness" of the procedure is called into question. there are certainly urologists who would be interested in doing this, and there are sexually violent predators with pedophilia who would prefer surgical castration over chemical castration (i've come across these case) but in practice they are receiving their shots of Lupron. as an aside, few psychiatrists are trained in the management of paraphilias and sex offenders, and few psychiatrists prescribe chemical castration so it is probably under utilized. it should be provided as part of a comprehensive treatment program including behavioral/psychological treatments and monitoring including structrured risk assessment measures, and possibly penile plethysmography. as an aside, in canada pedophiles are shown provocative images of children during such testing, but this is not allowed in the US so they just show them regular images of clothed children with audio sounds that are sexually charged.

Do you prefer to go over FDA limits on an antipsychotic or do you prefer adding another antipsychotic for a total of 2 antipsychotics (assuming these are the only two options)? Why?

 

[NewtonLeibniz]

Thank you all for the replies, keep them coming

 

[PsyDr]

@Crayola227 you would enjoy the story of Abelard and Helloise

 

[splik]

Do you prefer to go over FDA limits on an antipsychotic or do you prefer adding another antipsychotic for a total of 2 antipsychotics (assuming these are the only two options)? Why?

I'm not the best person to answer this question since I do not prescribe medications and am not primarily seeing pts with refractory psychosis, but I would prefer to max out one neuroleptic (including going above FDA licensed dose - off label prescribing is the rule in psychiatry) as long as the patient was tolerating it and you were seeing some response at lower doses. IMHO the only times it makes sense to use 2 neuroleptics is when one is clozapine (although the CARE study showed adding risperdal to clozapine was not any more effective), or abilify. it is also important to remember than 1 in 7 patients with "schizophrenia" do not respond to any neuroleptics whatsoever and we should try to minimize iatrogenic harm rather than flinging more and more of ineffective drugs at them.

 

[bashir]

I'm not the best person to answer this question since I do not prescribe medications and am not primarily seeing pts with refractory psychosis, but I would prefer to max out one neuroleptic (including going above FDA licensed dose - off label prescribing is the rule in psychiatry) as long as the patient was tolerating it and you were seeing some response at lower doses. IMHO the only times it makes sense to use 2 neuroleptics is when one is clozapine (although the CARE study showed adding risperdal to clozapine was not any more effective), or abilify. it is also important to remember than 1 in 7 patients with "schizophrenia" do not respond to any neuroleptics whatsoever and we should try to minimize iatrogenic harm rather than flinging more and more of ineffective drugs at them.

Do you by any chance have a citation for that 1 in 7 number? Sounds about right to me, although at least where I practice no one seems to have the guts to stop prescribing antipsychotics to non-responders. I once suggested it to an attending for a patient of mine who refused to try clozapine and had had no response to at least a half dozen other antipsychotics. He looked at me like I had two heads.

 

[clausewitz2]

I'm not the best person to answer this question since I do not prescribe medications and am not primarily seeing pts with refractory psychosis, but I would prefer to max out one neuroleptic (including going above FDA licensed dose - off label prescribing is the rule in psychiatry) as long as the patient was tolerating it and you were seeing some response at lower doses. IMHO the only times it makes sense to use 2 neuroleptics is when one is clozapine (although the CARE study showed adding risperdal to clozapine was not any more effective), or abilify. it is also important to remember than 1 in 7 patients with "schizophrenia" do not respond to any neuroleptics whatsoever and we should try to minimize iatrogenic harm rather than flinging more and more of ineffective drugs at them.

As someone who does chiefly work with psychosis at this point, I definitely appreciate the point about maxing out a single neuroleptic as long as there is response - I don't buy any of the current pharmacogenomic tests out there as anything but a waste of money and serum but there is every reason to believe there is not going to be an isomorphic relationship between dose taken by mouth, the "effective" dose that ever gets seen by the brain, and response that holds across all individuals. At the same time if we are legitimately talking about 2400 mg of Seroquel I think we are way beyond anything like a plausible range.

If someone was at 1400 and still symptomatic in a way that caused problems, I think it makes a lot more sense to try non-neuroleptic adjuncts that have at least some evidence behind them, like minocycline, celecoxib, sarcosine. Hell, even ashwaganda. It is not the case that the evidence base is less robust for these things than for mega doses of neuroleptics, but if you are considering such high doses you have to be cognizant of the fact that you are necessarily treating someone who does not have a great response to the medication in question. You can keep yanking the dopamine antagonism lever as much as you want but when you stop getting a payout you need to move on to another machine. Lamictal is probably also underused for augmenting clozapine and olanzapine relative to the data that exist.

The studies that have looked more carefully at individual response to neuroleptics tend to find about 10-15% who respond very quickly and dramatically, 50-60% who respond over a slower time course and only partially remit, and then the remainder who appear to get 0 benefit out of a therapeutic dose. Given that psychotic disorders tend to wax and wane over long time scales, you need to be careful you are not convincing yourself that people in the last category are actually in the second category.

As far as augmenting clozapine with neuroleptics go the only really good evidence seems to be for Abilify with Clozapine, and the data are actually more compelling for reducing metabolic side effects and weight gain (!) by adding this rather than better symptom control per se.

 

[NewtonLeibniz]

As someone who does chiefly work with psychosis at this point, I definitely appreciate the point about maxing out a single neuroleptic as long as there is response - I don't buy any of the current pharmacogenomic tests out there as anything but a waste of money and serum but there is every reason to believe there is not going to be an isomorphic relationship between dose taken by mouth, the "effective" dose that ever gets seen by the brain, and response that holds across all individuals. At the same time if we are legitimately talking about 2400 mg of Seroquel I think we are way beyond anything like a plausible range.

If someone was at 1400 and still symptomatic in a way that caused problems, I think it makes a lot more sense to try non-neuroleptic adjuncts that have at least some evidence behind them, like minocycline, celecoxib, sarcosine. Hell, even ashwaganda. It is not the case that the evidence base is less robust for these things than for mega doses of neuroleptics, but if you are considering such high doses you have to be cognizant of the fact that you are necessarily treating someone who does not have a great response to the medication in question. You can keep yanking the dopamine antagonism lever as much as you want but when you stop getting a payout you need to move on to another machine. Lamictal is probably also underused for augmenting clozapine and olanzapine relative to the data that exist.

The studies that have looked more carefully at individual response to neuroleptics tend to find about 10-15% who respond very quickly and dramatically, 50-60% who respond over a slower time course and only partially remit, and then the remainder who appear to get 0 benefit out of a therapeutic dose. Given that psychotic disorders tend to wax and wane over long time scales, you need to be careful you are not convincing yourself that people in the last category are actually in the second category.

As far as augmenting clozapine with neuroleptics go the only really good evidence seems to be for Abilify with Clozapine, and the data are actually more compelling for reducing metabolic side effects and weight gain (!) by adding this rather than better symptom control per se.

This is correct, but it was seemingly for one patient only.

According to some articles, he upped the dosage of that patient from 900mg seroquel to 1600mg, and then upped it again to 2400mg two months later.

Unfortunately I cannot find the actual judgements that would make all of this clearer and more detailed.I wouldn't know where to find this.

 

[dl2dp2]

... at least where I practice no one seems to have the guts to stop prescribing antipsychotics to non-responders. I once suggested it to an attending for a patient of mine who refused to try clozapine and had had no response to at least a half dozen other antipsychotics. He looked at me like I had two heads.

This is now considered fairly standard practice in community psychiatry for people with refractory psychosis. If you have psychosis and the meds are not doing anything and give you side effects, why would you continue? That makes no sense. Typically these people go to: 1) state hospital for long term hospitalization if aggressive/hard to manage outpatient 2) long term state day programs (this is by far the most common), get some wraparound services, etc. This is actually not a bad life. 3) clinical trials.