pdoc said atypicals are better?

[swanny]

my pdoc said atypicals are better than typical antipsychotics and never prescribes the old ones anymore BUT how are they better? better side effects? better effectiveness?

[Aurochs]

Atypicals don't seem to be any more or less effective than the older typical APs. For side effects, you trade EPS and neuroleptic malignant syndrome for weight gain and in extreme cases, diabetes. The medical community considers metabolic SEs favorable to EPS, and I'd honestly agree (metabolic SEs are manageable, but TD really isn't).

AAPs are also much, much more expensive.

[notfred]

Along with what the others said AAP's are better than AP's at treating negative symptoms.

nf

[vanderk]

There was a head to head study recently that cast the older meds (well, Trilafon, at least) in a positive light. But the study was more about compliance than efficacy. I believe the older meds are actually better for some folks, especially those with fixed delusions. But docs these days will virtually always throw a bunch of atypicals first before considering an older agent.

[nibblerd]

I think the move towards atypicals is because of the selectivity for different regions of the brain and receptor groups. The older antipsychotics were much less selective, working on not only the dopamine and serotonin system, but also a high affinity for the histamine and choline receptor groups leading to a higher level of sedation and side effects (though in some APs, the antihistamine side effects negate the anticholinergic side effects, like in Thorazine). It's also been said that the risk of extra-pyramidal side effects is lesser with atypicals, though I don't know if that's actually been proven. Clinical studies have shown lower rates of TD with the AAPs but I don't think those numbers reflect the results from real-world use. I wish I could design drugs as well as some people can; I'd totally make it my duty to develop a neuroleptic with few side effects.

With regards to efficacy, based on their receptor binding affinities I'd say they are very similar.

[AnneMarie]

I think the move towards atypicals is because of the selectivity for different regions of the brain and receptor groups. The older antipsychotics were much less selective, working on not only the dopamine and serotonin system, but also a high affinity for the histamine and choline receptor groups leading to a higher level of sedation and side effects (though in some APs, the antihistamine side effects negate the anticholinergic side effects, like in Thorazine). It's also been said that the risk of extra-pyramidal side effects is lesser with atypicals, though I don't know if that's actually been proven. Clinical studies have shown lower rates of TD with the AAPs but I don't think those numbers reflect the results from real-world use. I wish I could design drugs as well as some people can; I'd totally make it my duty to develop a neuroleptic with few side effects.

With regards to efficacy, based on their receptor binding affinities I'd say they are very similar.

Wait. First you say that old APs are more broad spectrum that AAPs, then you say their receptor binding affinities are very similar.

Do you have anything to back your statement that EPS is not less on atypicals?

[nibblerd]

I think the move towards atypicals is because of the selectivity for different regions of the brain and receptor groups. The older antipsychotics were much less selective, working on not only the dopamine and serotonin system, but also a high affinity for the histamine and choline receptor groups leading to a higher level of sedation and side effects (though in some APs, the antihistamine side effects negate the anticholinergic side effects, like in Thorazine). It's also been said that the risk of extra-pyramidal side effects is lesser with atypicals, though I don't know if that's actually been proven. Clinical studies have shown lower rates of TD with the AAPs but I don't think those numbers reflect the results from real-world use. I wish I could design drugs as well as some people can; I'd totally make it my duty to develop a neuroleptic with few side effects.

With regards to efficacy, based on their receptor binding affinities I'd say they are very similar.

Wait. First you say that old APs are more broad spectrum that AAPs, then you say their receptor binding affinities are very similar.

Do you have anything to back your statement that EPS is not less on atypicals?

I'm sorry, I wasn't very clear. Within the shared receptor sites (dopamine/serotonin), the affinities are similar.

http://focus.psychia...abstract/2/1/48

Conclusion: Atypicalsclinically help patients by transiently occupying D₂ receptorsand then rapidly dissociating to allow normal dopamine neurotransmission.This keeps prolactin levels normal, spares cognition, and obviatesEPS. One theory of atypicality is that the newer drugs block5-HT_2A receptors at the same time as they block dopamine receptorsand that, somehow, this serotonin-dopamine balance confers atypicality.This, however, is not borne out by the results. While 5-HT_2Areceptors are readily blocked at low dosages of most atypicalantipsychotic drugs (with the important exceptions of remoxiprideand amisulpride, neither of which is available for use in Canada)the dosages at which this happens are below those needed toalleviate psychosis. In fact, the antipsychotic threshold occupancyof D₂ for antipsychotic action remains at about 65% for bothtypical and atypical antipsychotic drugs, regardless of whether5-HT_2A receptors are blocked or not. At the same time, the antipsychoticthreshold occupancy of D₂for eliciting EPS remains at about80% for both typical and atypical antipsychotics, regardlessof the occupancy of 5-HT_2A receptors. Relevance:The "fast-off-D₂"theory, on the other hand, predicts which antipsychotic compoundswill or will not produce EPS and hyperprolactinemia and whichcompounds present a relatively low risk for tardive dyskinesia.This theory also explains why L-dopa psychosis responds to lowatypical antipsychotic dosages, and it suggests various individualizedtreatment strategies.

That theory leads to the incorrect conclusion that atypicals are not likely to produce EPS. I say incorrect because of an article I saw recently that claimed 5% of patients that experienced EPS in a clinical trial vs 63% of patients in real-world settings.. In reality, any drug which modulates the dopamine system this way will have a risk of EPS (like Abilify and akathisia, an acute form of EPS).

[domovoi]

dr. joel paris argues in his book that AAPs are not much better than typicals, at least in regards to effectiveness. he contends that typicals still should be used for the treatment of schizophrenia. however, AAPs are associated with less risk of tardive dyskinesia (not necessarily EPS). they have not been proven to treat negative symptoms either, though big pharma says they do. in the end, they don't make you shakey, they make you fat but they work the same. there is a lot of hype around them, though.

[confused]

The pdocs I've seen have put me on atypicals. They seem to have a preference for them, too. My understanding was there was a lower risk for TD with atypicals.

[Aurochs]

That theory leads to the incorrect conclusion that atypicals are not likely to produce EPS. I say incorrect because of an article I saw recently that claimed 5% of patients that experienced EPS in a clinical trial vs 63% of patients in real-world settings.

Please cite this article, as I would like to read it.

In reality, any drug which modulates the dopamine system this way will have a risk of EPS (like Abilify and akathisia, an acute form of EPS).

Nobody has ever said that any atypical antipsychotic was totally free of EPS, only that the incidence of EPS (especially dyskinesias) seems to be lower among AAPs than the older drugs.

[Velvet Elvis]

I think the move towards atypicals is because of the selectivity for different regions of the brain and receptor groups. The older antipsychotics were much less selective, working on not only the dopamine and serotonin system, but also a high affinity for the histamine and choline receptor groups leading to a higher level of sedation and side effects (though in some APs, the antihistamine side effects negate the anticholinergic side effects, like in Thorazine). It's also been said that the risk of extra-pyramidal side effects is lesser with atypicals, though I don't know if that's actually been proven. Clinical studies have shown lower rates of TD with the AAPs but I don't think those numbers reflect the results from real-world use. I wish I could design drugs as well as some people can; I'd totally make it my duty to develop a neuroleptic with few side effects.

With regards to efficacy, based on their receptor binding affinities I'd say they are very similar.

Haldal's increased risk of EPS in fact comes from the fact that it is too specific a dopamine antagonist. It's the purist dopamine blocker that's ever been devised but it turns out that's not what they wanted. I'd have to reread Stahl on dopamine pathways to explain the rest of the story, but in short DA specificity produces a greater risk of EPS than the AAPs which are active on more receptor types at more receptor sites.

[nibblerd]

That theory leads to the incorrect conclusion that atypicals are not likely to produce EPS. I say incorrect because of an article I saw recently that claimed 5% of patients that experienced EPS in a clinical trial vs 63% of patients in real-world settings.

Please cite this article, as I would like to read it.

In reality, any drug which modulates the dopamine system this way will have a risk of EPS (like Abilify and akathisia, an acute form of EPS).

Nobody has ever said that any atypical antipsychotic was totally free of EPS, only that the incidence of EPS (especially dyskinesias) seems to be lower among AAPs than the older drugs.

I tried finding that article but I was unsuccessful.. I'll keep looking for it, and I will definitely post it here if I find it.