Atypical Antipsychotics and PD psychosis ?

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susruta

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I am confused about how clozapine works better for pts with PD.
What is the mechanism by which Clozapine and Quetiapine work better for psychosis in patients with Parkinson's disease?

Thanks

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They're less anti-dopaminergic and so exacerbate less the low dopamine state that occurs in Parkinson's.
 
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Yeah, not necessarily better, or more effective, for the psychosis, but less likely to exacerbate Parkinson’s symptoms. For example, risperidone ‘might’ be more effective for someone’s psychosis, but totally destabilize the movement disorder.
 
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The evidence for Seroquel (quetiapine) is actually very limited, but people still go to it just because clozapine is very scary. Surprisingly enough outcomes with zyprexa have not been good and it's one of the meds to be avoided in patients with Parkinson's.
 
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The evidence for Seroquel (quetiapine) is actually very limited, but people still go to it just because clozapine is very scary. Surprisingly enough outcomes with zyprexa have not been good and it's one of the meds to be avoided in patients with Parkinson's.

people would prefer to go with Seroquel or Abilify as opposed to Clozapine due to the lab monitoring.
 
Actually clozapine is the most effective antipsychotic for PD psychosis and LBD typically we use 25-50mg/day so much tinier doses than in schizophrenia. Seroquel is largely useless. There is at least one study for abilify where it was tolerated but not effective. I have used it for psychotic depression in a pt who also had PD. Some people report significant worsening of Parkinson’s with abilify but I haven’t seen that. In general first line for psychosis is LBD is AChEIs like rivastigmine. In Parkinson’s psychosis try to remove anticholinergics, amantadine, dopamine agonists if possible and reduce sinemet If still problematic and possible. Seroquel is most commonly used but is rarely helpful other than sedating the pt and I would rather use other drugs to calm/sedate pts (e.g. trazodone in bad brains). Clozapine is actually a very powerful dopamine antagonist but because it very effectively fast dissociates from D2 receptors it does not induce the general badness you get in other neuroleptics. It’s certainly even more complicated than that but we don’t fully understand clozaril even though it’s receptor profile is well characterized it’s unclear how this translates into its effects. It’s woefully underused in PD psychosis and LBD psychosis.
 
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Clozapine is actually a very powerful dopamine antagonist
It has the lowest D2 receptor affinity besides Seroquel, and it has a higher affinity to several other receptors. Clozapine certainly binds to D2, but to call it "powerful" in that action seems like a stretch to me.
 
Anyone seeing good results with pimvanserin? I’ve seen several patients on it and never been impressed yet.
 
Actually clozapine is the most effective antipsychotic for PD psychosis and LBD typically we use 25-50mg/day so much tinier doses than in schizophrenia. Seroquel is largely useless. There is at least one study for abilify where it was tolerated but not effective. I have used it for psychotic depression in a pt who also had PD. Some people report significant worsening of Parkinson’s with abilify but I haven’t seen that. In general first line for psychosis is LBD is AChEIs like rivastigmine. In Parkinson’s psychosis try to remove anticholinergics, amantadine, dopamine agonists if possible and reduce sinemet If still problematic and possible. Seroquel is most commonly used but is rarely helpful other than sedating the pt and I would rather use other drugs to calm/sedate pts (e.g. trazodone in bad brains). Clozapine is actually a very powerful dopamine antagonist but because it very effectively fast dissociates from D2 receptors it does not induce the general badness you get in other neuroleptics. It’s certainly even more complicated than that but we don’t fully understand clozaril even though it’s receptor profile is well characterized it’s unclear how this translates into its effects. It’s woefully underused in PD psychosis and LBD psychosis.

Agree with above. Although I think it’s fair to make the argument that the concrete brick constipation that patients will develop is a risk in geriatrics especially. Im surprised that seroquel has been found ineffective. I think it’s often not dosed high enough, but quite effective in relieving psychosis in the patients we treated in Gero. Then it becomes a problem of sedation though, as you mention. Thanks for bringing some sense to this thread.
 
I've seen one successful case with pimavanserin.

But yes, Clozaril seems to be the go to.
 
Agree with above. Although I think it’s fair to make the argument that the concrete brick constipation that patients will develop is a risk in geriatrics especially. Im surprised that seroquel has been found ineffective. I think it’s often not dosed high enough, but quite effective in relieving psychosis in the patients we treated in Gero. Then it becomes a problem of sedation though, as you mention. Thanks for bringing some sense to this thread.

I was told by my Geri Psych attending not to go higher than 200 mg of Seroquel in elderly due to concerns of falls/sedations.
 
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I was told by my Geri Psych attending not to go higher than 200 mg of Seroquel in elderly due to concerns of falls/sedations.

Yeah... unfortunately psychosis puts you at risk of a lot worse. That said, it should only be used when absolutely necessary and at the minimum effective dose.
 
That said, If you can get a patients hallucinations to be tolerable, these people can do just fine.
 
No one here as mentioned Nuplazid? I don't treat this population, so I'm not sure how practically available it may be.
 
I was told by my Geri Psych attending not to go higher than 200 mg of Seroquel in elderly due to concerns of falls/sedations.

Yeah... unfortunately psychosis puts you at risk of a lot worse. That said, it should only be used when absolutely necessary and at the minimum effective dose.

From The Last Psychiatrist it seems that increasing doses of Seroquel may not necessarily be more sedating, and the minimum effective dose may be a concept that doesn't apply as it normally would in a typical linear dose response:

The Last Psychiatrist: The Most Important Article On Psychiatry You Will Ever Read
 
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