Seroquel--the worst antipsychotic?

[jbomba]

It's been a while. The only old-school neuroleptic I use apart from haldol is fluphenazine once in a while, to be honest.

I've been using loxapine recently. Particularly in patients who had good response to clozapine but couldn't continue for any number of reasons.

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[mistafab]

I know for stahl worshippers out there - specific receptors are really important. Not discounting receptor importance, but stahl can be smart and irrational sometimes.

An empiricist like me just goes to the data. The FDA package insert for seroquel has the pivotal trials for seroquel for each indication that got approved. For schizophrenia it seems you need around 400 mg minimum dose for effectiveness. For bipolar depression, it may be lower - possibly as low as 150 mg minimum.

 

[docksan]

I know for stahl worshippers out there - specific receptors are really important. Not discounting receptor importance, but stahl can be smart and irrational sometimes.

An empiricist like me just goes to the data. The FDA package insert for seroquel has the pivotal trials for seroquel for each indication that got approved. For schizophrenia it seems you need around 400 mg minimum dose for effectiveness. For bipolar depression, it may be lower - possibly as low as 150 mg minimum.

A large part of this is placebo and provider relationship. I find the utility of Seroquel beyond 400mg long term to be worthless compared to other agents specifically because of receptor profile and predictable side effects. You can't just ignore that.

You also have to bear in mind the trials are a controlled set of circumstances that don't account for more practical situations. It would be silly to say receptor profile are irrational sometimes. You can't change how chemistry works.

 

[forchinet121]

A large part of this is placebo and provider relationship. I find the utility of Seroquel beyond 400mg long term to be worthless compared to other agents specifically because of receptor profile and predictable side effects. You can't just ignore that.

You also have to bear in mind the trials are a controlled set of circumstances that don't account for more practical situations. It would be silly to say receptor profile are irrational sometimes. You can't change how chemistry works.

You nor anyone else knows how the chemistry works..don’t overstate your understanding..I have people on 1000 mg of Seroquel and that’s the only thing that has kept their treatment refractory symptoms in check..we don’t truly know how these meds work and know even less about how they interact together

 

[docksan]

You nor anyone else knows how the chemistry works..don’t overstate your understanding..I have people on 1000 mg of Seroquel and that’s the only thing that has kept their treatment refractory symptoms in check..we don’t truly know how these meds work and know even less about how they interact together

All of science is theory with little understanding due to the limits of observation.

What are you even talking about?

 

[forchinet121]

All of science is theory with little understanding due to the limits of observation.

What are you even talking about?

All of science is theory? So you’re equating our understanding of the shoulder joint and the pathology that can happen with the shoulder to schizophrenia and the pathology that happens in the brain? In medicine there are things we understand better than others..so no, it’s not all theory.

 

[G Sheb]

You nor anyone else knows how the chemistry works..don’t overstate your understanding..I have people on 1000 mg of Seroquel and that’s the only thing that has kept their treatment refractory symptoms in check..we don’t truly know how these meds work and know even less about how they interact together

Right.
Our understanding of psychosis is so primitive that the idea you think this or that medication works better because of this 'receptor', when the empirical data of efficacy doesn't really justify that conclusion, is utterly laughable.
This is not science or EBM.
As I said in another thread, this kind of nonsense seems to be way more prevalent, tolerated and encouraged in psychiatry than in other medical specialties. It has to do with the culture and what is being taught in residencies.

 

[docksan]

All of science is theory? So you’re equating our understanding of the shoulder joint and the pathology that can happen with the shoulder to schizophrenia and the pathology that happens in the brain? In medicine there are things we understand better than others..so no, it’s not all theory.

No, I'm saying that's what you're doing.

The brain is a poorly understood organ that certain receptors and areas seem to respond to certain medications without a clear reason as to why.

Ignoring this is like ignoring why ARBs or CCBs work, and then pulling a Joe Dirt and saying "They just do".

Nice strawman though.

 

[Stagg737]

I know for stahl worshippers out there - specific receptors are really important. Not discounting receptor importance, but stahl can be smart and irrational sometimes.

An empiricist like me just goes to the data. The FDA package insert for seroquel has the pivotal trials for seroquel for each indication that got approved. For schizophrenia it seems you need around 400 mg minimum dose for effectiveness. For bipolar depression, it may be lower - possibly as low as 150 mg minimum.

Sure, but we also have to understand the limits of the data. I think FDA inserts are great references, but the data is often limited or summarized to the extent that we don't think about it critically if taken at face value. For Seroquel for schizophrenia, it references 3 trials which were all only 6 weeks and doesn't give any statistical points of those studies. Not the most thorough examination or robust data... We can also look at plenty of other data as well, but what do we do when multiple well-run studies all say different things? How do we reconcile that?

What about unpublished data? I've seen one or two papers/trials and talked to some reliable sources that had robust data which wasn't published d/t certain companies not wanting the data released. Do we just trust big name journals? Do you stick to the "EBM" when you know there's evidence directly contradicting it?

And what about confounding factors? Clozapine is pretty regularly considered the most effective antipsychotic, but there's still concerns regarding how much frequency of monitoring/follow-up d/t monitoring requirements plays a role in longer-term outcomes. So is it really that much better outside of acute settings? If it's not, what does that say about current practices?

What about individual differences? If you had a patient who did well with haldol and risperidone but had side effects, and meds like olanzapine and quetiapine showed no effect, doesn't it make sense to choose a next option that is more similar to haldol/risperidone? Or do you go with clozapine because that's what the algorithm says? What do you do when the algorithm fails?

I'm not going to argue what's right or wrong for any of those answers. I do sometimes prescribe quetiapine, and acknowledge that it works for some, but I think there are options that are generally more efficacious with a much lower side effect burden. I try to follow EBM, but also understand EBM is a set of guidelines meant to direct care for certain populations/demographics and that we shouldn't disregard clinical judgment for each individual case. If we're just going to use algorithms based on current data, why do we even exist? We may as well just replace ourselves with AI and upload new data as it becomes apparent. Imo, the reason specialists exist, including psychiatrists, is to identify and treat uncommon or severe conditions outside the scope of generalists or for situations where the algorithms are failing.

 

[comp1]

The problems with ziprasidone is that it has to be taken with food. And asking psychotic people to not only take medications bid, but also with food...is quite simply not reasonable. There are not massive differences between the antipsychotics, but the best studies do separate out olanzapine and the slightly less better studies can still separate out clozapine pretty universally. I doubt that we would be able to observe a difference with olanzapine through our own anecdotal experience given the effect size.

 

[ObsequiousAplomb]

The problems with ziprasidone is that it has to be taken with food. And asking psychotic people to not only take medications bid, but also with food...is quite simply not reasonable. There are not massive differences between the antipsychotics, but the best studies do separate out olanzapine and the slightly less better studies can still separate out clozapine pretty universally. I doubt that we would be able to observe a difference with olanzapine through our own anecdotal experience given the effect size.

I'm a little confused as to why you are saying the best studies separate olanzapine and slightly less better ones separate clozapine. AFAIK, the clozapine studies are some of the best head-to-head studies we have of any APs. Clozapine comparative efficacy is the primary outcome. They very clearly demonstrate superiority.

The studies separating olanzapine tend to be weaker and rely on secondary outcomes to come to those conclusions.

I would say the data very clearly demonstrates clozapine superiority and mildly suggests that olanzapine might be a second place option.

 

[docksan]

The problems with ziprasidone is that it has to be taken with food. And asking psychotic people to not only take medications bid, but also with food...is quite simply not reasonable. There are not massive differences between the antipsychotics, but the best studies do separate out olanzapine and the slightly less better studies can still separate out clozapine pretty universally. I doubt that we would be able to observe a difference with olanzapine through our own anecdotal experience given the effect size.

Except they don't separate out olanzapine nearly to the degree that clozapine jumps ahead in its studies.

 

[Shikima]

Not to hijack the thread in talking about Seroquel (and Zyprexa to a lesser degree), what are the thoughts about Loxapine? Strangely, I've been having good success with using it for various populations where polypharmacy was necessary to control mania, depression and psychosis.

 

[Mad Jack]

I've been using loxapine recently. Particularly in patients who had good response to clozapine but couldn't continue for any number of reasons.

Not to hijack the thread in talking about Seroquel (and Zyprexa to a lesser degree), what are the thoughts about Loxapine? Strangely, I've been having good success with using it for various populations where polypharmacy was necessary to control mania, depression and psychosis.

Loxapine is one of the most underrated drugs out there. While we don't have as robust of results on it as clozapine, it doesn't cause the significant metabolic issues associated with clozapine and I've had great success with it when working with some patients in the past.

 

[Stagg737]

Not to hijack the thread in talking about Seroquel (and Zyprexa to a lesser degree), what are the thoughts about Loxapine? Strangely, I've been having good success with using it for various populations where polypharmacy was necessary to control mania, depression and psychosis.

Agree with MJ, I actually like it a lot for the right patients and like seroquel has a somewhat broad dosing range, so can be used at lower doses for agitation/impulsivity. It's one of my go-to meds for patients with ID/severe ASD with significant agitation when stuff like abilify or risperdal isn't working.

From a molecular standpoint, it's pretty similar to clozapine and is metabolized to amoxapine which is a TCA (discontinued in the US but still used in other countries). Anecdotally I have found it to be helpful for patients with schizophrenia or other issues with co-morbid depression. I don't use loxapine for bipolar/mania d/t it metabolizing to amoxapine which has a listed side effect of (hypo)mania, but honestly don't know the data for using it for bipolar disorders.

ETA: Apparently a systematic review found it has indications for manic agitation, but has not been studied for actual treatment of manic episodes:

Revisiting loxapine: a systematic review - Annals of General Psychiatry

Loxapine is an antipsychotic used in psychiatry for over 40 years with a well-established profile. Loxapine is a dibenzoxazepine tricyclic antipsychotic agent, available for oral, intramuscular and inhalatory administration. In the light of the recent approval by the regulatory agencies of...

annals-general-psychiatry.biomedcentral.com

 

[Ceke2002]

People seemed to like my Sunday morning musings last week so here's another.

I dislike seroquel intensely. Which doesn't mean I don't use it. But, reasons I hate it--

1. Makes people fat. Recently was looking through data on metabolic effects and was shocked in the literature it's not shown to be one of the worst. My experience is people gain tons of weight.

2. Orthostatic hypotension. I do a lot of geri and CL, so seroquel is obviously often a theoretical first line for pts with Parkinson or LBD. But goddam the orthostatic hypotension is real and dangerous. And you also get people who have been on it for decades who become vasculopaths as they get older and its a real problem.

3. It's so hard to wean. Even with cooperative patients it's hard. Sometimes I'd rather be weaning a benzo.

4. Related to #3, seroquel is the only non-controlled med I've been SCREAMED at when a patient needed a refill or wanted restarted in the hospital. The other times that happens are benzos and Adderall. Really makes one think, no? We know it has "abuse potential" but that's said of wellbutrin too and no one has ever melted down at me to get their wellbutrin. Or gabapentin.

5. Does it even antipsychotic? Yeah, yeah, we all know that doses need to be high to get dopamine blockade. I just can't shake the feeling it doesn't do its job on that front. If I am going to make someone gain a ton of weight I may as well give them olanzapine. At least that's an effective antipsychotic.

6. I want to be able to put people straight on latuda and vraylar for bipolar depression but get stuck in prior Auth hell unless they've tried seroquel. Hate.

What's your experience been?

Personal experience from having taken it myself:

At a higher dose (max 1200 mgs off label for treatment of anxiety & insomnia) - ridiculous levels of weight gain and bloating, triggered episodes of bingeing, had to make sure I didn't stand up to quick or there was every chance I'd fall flat on my face, dizziness, light headedness plus other symptoms associated with orthostatic hypotension, no issues coming off (maybe because it was a huge relief coming off it). Didn't really do anything to help anxiety or insomnia, even at high dosage.

At a lower dose (max 2-300mgs for treatment of psychotic features of 'psychotic depression') - only marginal weight gain, little to no effects of orthostatic hypotension, tolerated quite well at first, didn't stop auditory (etc) hallucinations but toned everything way down (much easier to deal with), coming off was a bit of an issue because the psychotic features ratcheted up to 11 for a week or so (annoying but still manageable with support). Despite efficacy & initial low side effect profile, I was eventually pulled off it due to some heart thing, long S or Q something or other, I don't remember exactly.

 

[Shikima]

Agree with MJ, I actually like it a lot for the right patients and like seroquel has a somewhat broad dosing range, so can be used at lower doses for agitation/impulsivity. It's one of my go-to meds for patients with ID/severe ASD with significant agitation when stuff like abilify or risperdal isn't working.

From a molecular standpoint, it's pretty similar to clozapine and is metabolized to amoxapine which is a TCA (discontinued in the US but still used in other countries). Anecdotally I have found it to be helpful for patients with schizophrenia or other issues with co-morbid depression. I don't use loxapine for bipolar/mania d/t it metabolizing to amoxapine which has a listed side effect of (hypo)mania, but honestly don't know the data for using it for bipolar disorders.

ETA: Apparently a systematic review found it has indications for manic agitation, but has not been studied for actual treatment of manic episodes:

Revisiting loxapine: a systematic review - Annals of General Psychiatry

Loxapine is an antipsychotic used in psychiatry for over 40 years with a well-established profile. Loxapine is a dibenzoxazepine tricyclic antipsychotic agent, available for oral, intramuscular and inhalatory administration. In the light of the recent approval by the regulatory agencies of...

annals-general-psychiatry.biomedcentral.com

Personal experience, just by trying something on a whim because all other medication has failed, did work in addressing bipolar symptoms pulling people out of mania and/or depression.
I haven't seen anyone become manic on this medication. Thanks for the feedback.

 

[splik]

From a molecular standpoint, it's pretty similar to clozapine and is metabolized to amoxapine which is a TCA (discontinued in the US but still used in other countries). Anecdotally I have found it to be helpful for patients with schizophrenia or other issues with co-morbid depression.

Amoxapine is still available! I've never used it and never seen it used. It has a risk of seizure in overdose as well as renal impairment (probably due to rhabdo) in addition to the other badness that comes with TCAs. which means loxapine also has those risks. in addition I've had some patients have bad dystonic reactions to loxapine which you never get with clozapine. We used loxapine a lot during residency. I have never used it since but I rarely work inpatient, and it's not a good option for my patient population.