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  • N&PD Moderators: Skorpio

Treating Schizophrenia with Nuplazid ?

Just reading the AI results-- why is it effective for Parkinson's hallucinations but is labeled as a serotonergic mechanism? (What does a selective 5ht2a drug fix dopamine disease?)
 
In my own lifetime I've read four variations on the schizophrania hypothesis.

I'm very driven and long ago two things were noted in the cerbrospinal fluid of people who were subject to schizoprenia:

1-Elevated levels of DOPAC (a dopamine metabolite)
2Supressed levels of NMDA

Now around 90% of suffers have 1 and 2 while a 10% of all cases only demonstate 2 which is why that class of novel NMDA modulators worked brilliantly for 10% of sufferers, was of no value to the 90% so was dropped. THAT angered me because the class was vastly better tolerated and produced far fewer side-effects but would only ever be a 'niche' product. BUT we may cautiously state that in cases where decresed levels of NMDA are the sole biomarker, modulation of NMDA can be a succesful treatment option.

But I have yet to see any other class of antipsychotic that did not act on the dopamine receptors essentially to block the action of dopamine.

I suggest that it was almost an accidental discovery that medications that also had significant affinity for the 5HT2 receptors (all antipsychotics seemingly being highly promiscuous) so it may well be the case that certain elements of thought disorder are indirectly mediated via the serotonin receptors.

It's just that there are both positive and negative symptoms and I may be wrong but I believe a person only subject to positive symptoms (thought disorders) MAY still be prescribed an antipsychotic because as with all mental illnesses, self-reporting is a key-plank of diagnosis and sad to say paranoia can be a prominent symptom i.e. suggerers may under-report what they just see part of their character rather than part of the illness.

It's become pretty obvious that almost nobody fits into a single neat DSM criteria-based box. That personality disorders are associated and may be at least a driver of the ilness.

So while it would be lovely if a simple 5HT2a antagonist solved all of the thought-disorder symptoms so that councelling rather than a true antipsychotic needs to be prescrbed.

We still know so little about schizophrania. Why in monozygotic twins onlyin 50% of cases will both (identical) twins develop the illness. Why the genetic disadvantage means it's still present in similar percentages of the population as it ever was and if it historically offered a genetic advantage or that individuals that have ALL the biomarkers can be asymptomatic.

Although not strictly medical texts, Foucoult works 'Mental Illness and Psychology', 'Madness and Civilization' and 'Psychiatric Power: Lectures at the Collège de France, 1973–1974' all examine how schizophrnia became 'medicalized' and how before modern medicine people who today we may label 'schizophenic' were viewed as in some way being in closer contact with god; were supported by their community and seemingly were accepted.
 
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Ozymandeus said:
Just reading the AI results-- why is it effective for Parkinson's hallucinations but is labeled as a serotonergic mechanism? (What does a selective 5ht2a drug fix dopamine disease?)
Click to expand...
Just completely handwaving right here, but I would expect the hallucinations from Parkinson's to possibly be linked to some serotonergic circuit. Even if their cause is dysfunction of dopaminergic circuits, possibly antagonizing 5HT-2A could help treat those symptoms (like how clonidine helps with some aspects of opioid withdrawal despite not being an opioid).

4DQSAR said:
In my own lifetime I've read four variations on the schizophrania hypothesis.

I'm very driven and long ago two things were noted in the cerbrospinal fluid of people who were subject to schizoprenia:

1-Elevated levels of DOPAC (a dopamine metabolite)
2Supressed levels of NMDA

Now around 90% of suffers have 1 and 2 while a 10% of all cases only demonstate 2 which is why that class of novel NMDA modulators worked brilliantly for 10% of sufferers, was of no value to the 90% so was dropped. THAT angered me because the class was vastly better tolerated and produced far fewer side-effects but would only ever be a 'niche' product. BUT we may cautiously state that in cases where decresed levels of NMDA are the sole biomarker, modulation of NMDA can be a succesful treatment option.

But I have yet to see any other class of antipsychotic that did not act on the dopamine receptors essentially to block the action of dopamine.

I suggest that it was almost an accidental discovery that medications that also had significant affinity for the 5HT2 receptors (all antipsychotics seemingly being highly promiscuous) so it may well be the case that certain elements of thought disorder are indirectly mediated via the serotonin receptors.

It's just that there are both positive and negative symptoms and I may be wrong but I believe a person only subject to positive symptoms (thought disorders) MAY still be prescribed an antipsychotic because as with all mental illnesses, self-reporting is a key-plank of diagnosis and sad to say paranoia can be a prominent symptom i.e. suggerers may under-report what they just see part of their character rather than part of the illness.

It's become pretty obvious that almost nobody fits into a single neat DSM criteria-based box. That personality disorders are associated and may be at least a driver of the ilness.

So while it would be lovely if a simple 5HT2a antagonist solved all of the thought-disorder symptoms so that councelling rather than a true antipsychotic needs to be prescrbed.

We still know so little about schizophrania. Why in monozygotic twins onlyin 50% of cases will both (identical) twins develop the illness. Why the genetic disadvantage means it's still present in similar percentages of the population as it ever was and if it historically offered a genetic advantage or that individuals that have ALL the biomarkers can be asymptomatic.

Although not strictly medical texts, Foucoult works 'Mental Illness and Psychology', 'Madness and Civilization' and 'Psychiatric Power: Lectures at the Collège de France, 1973–1974' all examine how schizophrnia became 'medicalized' and how before modern medicine people who today we may label 'schizophenic' were viewed as in some way being in closer contact with god; were supported by their community and seemingly were accepted.
Click to expand...
I personally suspect that schizoprenia is a developmental disorder (like how autism spectrum disorders are typified by impaired synaptic pruning), where the topology of different circuits is more important than issues with any specific neurotransmitter system. I have a hard time assigning NMDA and DOPAC levels as causal or as a consequence of more fundamental structural changes.

MedicinalUser247 said:
@Skorpio Can you give us an Explanation ?
Click to expand...
This is getting pretty far from the core of my knowledge. I would say the best way to know is to test it- if it works, it may have fewer side effects than a more promiscuous drug, but it may not work for everyone.
 
But that twin study does confuse me.

I've known one pair of monozygotic twins where both developed schizophrania and another where only one developed it.

All dead now, which is ultimately the awful thing about the disease. With or without medication life-expectancy goes down by a decade (for muliple reasons).
 
The dopamine vs serotonin hypothesis is very interesting. Like the dopamine salience theory which explains hallucinatory delusions.

I don't have schizophrenia, but I have experienced kratom induced psychosis (which often is initially misdiagnosed as schizophrenia because some of the symptoms are identical). I've also experienced dopaminergic induced psychosis from stimulants. I've also experienced LSD induced psychosis.

They all have their different flavors, and they all seem to be exacerbated in unique ways.
 
Ive had psychosis years ago and honestly its nothing like a serotonic psychedelic. Most resembles dramamine imo. Dont think something that affects only serotonin would be that effective for schizophrenia
 
Kratom induced psychosis was far stranger than stimulant or LSD psychosis. The latter two seemed to create external hallucinations, things I could easily identify as hallucinations.

Kratom psychosis was different. The hallucinations were more internal. Had alienated thoughts which was so strange. That inner dialog became someone else. I would hear my own voice saying things I did not think of. It was like there was literally someone who hijacked my mind, killed the pilot, stole his uniform and started pushing buttons. It was bizzare.
 
paranoid android said:
Ive had psychosis years ago and honestly its nothing like a serotonic psychedelic. Most resembles dramamine imo. Dont think something that affects only serotonin would be that effective for schizophrenia
Click to expand...

I'm so glad you mentioned that.

Muscarinic receptors are the latest target.

Can I ask if you use nicotine? The reason being that until it's use was limited in UK psychiatric wards, 95% of the patients would chain-smoke because both nicotinic and muscarenic receptors are cholinergic receptors.

I may be wrong but I seem to recall someone did study nicotinic receptors but ligands get toxic REALLY fast.

But I estimated that nicotine use was just self-medication.

20 years ago once an hour patients would be allowed to go into a (secure) outside area to smoke and holy cow, the queues would start forming 20 minutes before fag-break times.

That was/is one reason why life expectancy is so low.

I even noted patients prescribed nicotine patches could just stop smoking. I mean just STOP. Again, I may only estimate but if they only smoked as self-medication, giving that medication in a much safer form seems like a no-brainer to me but typical, after 6 months prescriptions were halted because of costs. As if a person getting a cancer of the respiratory tract is the cost-free option!
 
Well... The doctor said yes to my experiment, The only problem was it wasn't covered by my insurance so I couldn't proceed with it. It would cost $5000 Dollars out of pocket for me to conduct my experiment. And I said no I don't have the Money for it. Well, I guess I can't do anything until the insurance company can approve it for Schizophrenia. :confused:
 
Some generic antidepressants are 5HT2a antagonists. I think mitrazipine is a potent 5HT2a angagonist, for example.

Cost ≠ effaciacy.

Just because something is a 50+ year old generic doesn't mean it isn't the best option.

But fuck man, you're young. Look after yourself so you end up at the very bottom of that statistical drop in lifespan.
 
4DQSAR said:
I'm so glad you mentioned that.

Muscarinic receptors are the latest target.

Can I ask if you use nicotine? The reason being that until it's use was limited in UK psychiatric wards, 95% of the patients would chain-smoke because both nicotinic and muscarenic receptors are cholinergic receptors.

I may be wrong but I seem to recall someone did study nicotinic receptors but ligands get toxic REALLY fast.

But I estimated that nicotine use was just self-medication.

20 years ago once an hour patients would be allowed to go into a (secure) outside area to smoke and holy cow, the queues would start forming 20 minutes before fag-break times.

That was/is one reason why life expectancy is so low.

I even noted patients prescribed nicotine patches could just stop smoking. I mean just STOP. Again, I may only estimate but if they only smoked as self-medication, giving that medication in a much safer form seems like a no-brainer to me but typical, after 6 months prescriptions were halted because of costs. As if a person getting a cancer of the respiratory tract is the cost-free option!
Click to expand...

Yup i smoke and about everyone n the psych ward i was in smoked to
 
People were developing α7 Nicotinic agonists for use in treating cognititive deficits in schizophrenia.

I have a large number of them in my database. However, not a single one actually passed all of the clinical trials AFAIK.
 
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