drug-induced schizophrenia

[tkadm30]

How can long-term neuroleptic drug (not cannabis) usage trigger psychosis? Is it possible that atypical antipsychotics inverse chemical balance (dopamine/serotonin levels) in the brain? Can atypical antipsychotics cause dopamine hypersensitivity?

 

Thanks.

Edited February 13, 2017 by tkadm30

[Lord Antares]

Is it possible that atypical antipsychotics inverse chemical balance (dopamine/serotonin levels) in the brain?

 

Every stimulant drug does that so it's not the explanation. Search for information about meth or speed (European). Cocaine induces a degree of psychosis, but not to the extent that amphetamine base and methamphetamine do.

They have the most prominent effects, including paranoia, hallucinations, delusions (about somewhone following them, police chasing them, conspiracy theories etc.), thought disorder, and especially eerie, ''meth mites''.

 

I did a quick search on google, and not one single link explains how this happens. They all explain diagnoses, effects, statistics etc. but you could conclude that it's unknown as to how exactly do these drugs trigger psychosis.

 

Here's an article on experiments and statistics you might find of use:

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280383/

[StringJunky]

 

Every stimulant drug does that so it's not the explanation. Search for information about meth or speed (European). Cocaine induces a degree of psychosis, but not to the extent that amphetamine base and methamphetamine do.

They have the most prominent effects, including paranoia, hallucinations, delusions (about somewhone following them, police chasing them, conspiracy theories etc.), thought disorder, and especially eerie, ''meth mites''.

 

I did a quick search on google, and not one single link explains how this happens. They all explain diagnoses, effects, statistics etc. but you could conclude that it's unknown as to how exactly do these drugs trigger psychosis.

 

Here's an article on experiments and statistics you might find of use:

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280383/

I think mental exhaustion from being awake too long and for too often , and being a dopamine agonist is the key to amphetamine hallucinations.

[Lord Antares]

Yes, being awake for too long is a large factor (the main one, as far as I'm concerned), but trust me, it's a lot different than just being awake for too long.

Apart from the effects, one other big difference is that you would be dead-tired after not having slept for 2-3 days while sober, while you might not be sleepy at all during speed comedown.

 

I agree with you that the key is being a dopamine agonist PLUS staying awake for too long, but I do think there is more to it and that there are other differences.

[StringJunky]

Yes, being awake for too long is a large factor (the main one, as far as I'm concerned), but trust me, it's a lot different than just being awake for too long.

Apart from the effects, one other big difference is that you would be dead-tired after not having slept for 2-3 days while sober, while you might not be sleepy at all during speed comedown.

 

I agree with you that the key is being a dopamine agonist PLUS staying awake for too long, but I do think there is more to it and that there are other differences.

I know, I had to take some kind of depressant to make me sleep otherwise I was heading for psychosis. There will be other things going on as it affects most parts of the body in some way.

[Lord Antares]

Ha. You are the last person I would expect to take drugs.

I didn't have access to sleeping pills because I had eaten them all previously so I would have to go through psychosis every single time.

 

By the way, do you find "speed sleep" interesting? I find it very, very weird and interesting. OP might want to research that because that's another difference between just not sleeping for a long time and not sleeping for a long time while on a comedown. It's a very unique feeling.

[tkadm30]

Can atypical antipsychotics inverse dopamine sensitivity?

[Lord Antares]

What do you mean by atypical antipsychotics? I guess what applies to ''tyipical'' antipsychotics also applies to atypical ones, seeing how both are classified as antipsychotics.

[tkadm30]

Atypical antipsychotics (inverse dopamine agonists) are thought to cause fewer extrapyramidal symptoms than typical antipsychotics.

[Lord Antares]

But wait just a minute.

 

First you asked:

 

Can atypical antipsychotics inverse dopamine sensitivity?

 

Then you said:

 

 

Atypical antipsychotics (inverse dopamine agonists)

 

You just answered your own question. You said that Atypical antipsychotics ARE inverse dopamine agonists, which neccessarily means that they do inverse dopamine sensitivty. Then you stated that they:

 

 

are thought to cause fewer extrapyramidal symptoms than typical antipsychotics.

 

So what is the question here exactly? It looks more like a statement to me than a question.

[tkadm30]

But wait just a minute.

 

First you asked:

 

 

Then you said:

 

 

 

You just answered your own question. You said that Atypical antipsychotics ARE inverse dopamine agonists, which neccessarily means that they do inverse dopamine sensitivty. Then you stated that they:

 

 

 

So what is the question here exactly? It looks more like a statement to me than a question.

 

Can inverse (partial) agonism at dopamine D2 receptors trigger dopaminergic hypersensitivity?

[Lord Antares]

Seems so:

 

https://www.ncbi.nlm.nih.gov/pubmed/1130936

 

https://www.ncbi.nlm.nih.gov/pubmed/574284

 

https://www.karger.com/Article/Pdf/117686

 

Although it seems that female rats did not show any signs of hypersensitivity. Other than that, it looks to be true.

But it seems like you already knew that.

[tkadm30]

Seems so:

 

https://www.ncbi.nlm.nih.gov/pubmed/1130936

 

https://www.ncbi.nlm.nih.gov/pubmed/574284

 

https://www.karger.com/Article/Pdf/117686

 

Although it seems that female rats did not show any signs of hypersensitivity. Other than that, it looks to be true.

But it seems like you already knew that.

 

I doubt seriously atypical antipsychotics are comparable to amphetamines. Apart from that, I guess partial (inverse) dopamine agonists doesn't block dopamine receptors like dopamine antagonists.

[Lord Antares]

''The ability of the drug to block the action of dopamine (DA)''

 

referring to atypical antipsychotics, so how would you guess that?

 

Source:

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC167197/

 

I think this article might answer all your questions.

[tkadm30]

Not all atypical antipsychotics are classical dopamine antagonists (blockers). For example, aripiprazole acts like a dopamine D2R antagonist under high extracellular concentration of dopamine. Under low dopaminergic tone, aripiprazole is a selective D2R ligand (agonist):

 

 

Under high dopaminergic tone, aripiprazole acts as a D₂-like autoreceptor antagonist rather than as an agonist. These data show that, ex vivo, alteration of dopaminergic tone by depolarization affects the actions of aripiprazole on D₂-like autoreceptors. Such unusual effects were not seen with the typical partial agonist preclamol and are consistent with the hypothesis that aripiprazole is a functionally selective D₂R ligand.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360222/

 

I'm curious about how theses ex vivo alterations of dopaminergic tone may affect differential sensitivity to dopamine agonists. Could a dopamine system stabilizer like aripiprazole trigger neuroleptic malignant syndrome (NMS) ?

[jbn22]

1.) Postsynaptic dopamin receptors fluctuate in density. This can be influenced by pharmaceuticals, but other environmental or endogenous factors aswell. This feature is not specific for dopamine receptors, but can occur in other neurotransmitter systems as well. This is relevant in clinical settings because it requires constant vigilance for EPS in order to determine the correct dosage. A patient that may be on a neuroleptic for years may still develop early-onset EPS without a change in serum concentration. Similarly, a patient may exhibit psychosis without a change in serum concentration. Both observations show (clinically) that pharmacodynamic effects can vary with time.

 

2.) Aripiprazole rarely causes MNS, but some cases have been reported.

 

----

 

I am unsure as to what cases of "antipsychotics causing psychosis" you're referring to. I haven't seen such a case yet (which doesn't mean they don't exist, I'm just curious as to where you picked that up). I would expect antipsychotics to cause or aggravate negative symptoms, but not productive psychosis.

[tkadm30]

 

I am unsure as to what cases of "antipsychotics causing psychosis" you're referring to. I haven't seen such a case yet (which doesn't mean they don't exist, I'm just curious as to where you picked that up). I would expect antipsychotics to cause or aggravate negative symptoms, but not productive psychosis.

 

Neuroleptic-induced ex vivo dopamine alterations may negatively affect dopamine neurotransmission and hippocampal synaptic plasticity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597980/

 

Impaired synaptic plasticity and NMDA receptor hypofunction are prevalent models of drug-induced schizophrenia.

[metacogitans]

How can long-term neuroleptic drug (not cannabis) usage trigger psychosis? Is it possible that atypical antipsychotics inverse chemical balance (dopamine/serotonin levels) in the brain? Can atypical antipsychotics cause dopamine hypersensitivity?

 

Thanks.

Psychosis from psychoactive substances is in almost all cases reversible and temporary, lasting 1-2 weeks at most.

Ah, now I see neuroleptic withdrawals are the cause. Yes, they are awful, and completely paradoxical - a leftover from old psychiatry when incapacitating a patient was the desired effect of medication.

Although I don't think psychosis from withdrawal should last very long, there are other serious neurological disorders that often come with long-term use of neuroleptics and cessation of taking them, such as psychomotor 'tics' (involuntary muscle movements, and inability to change thoughts or speech patterns, slightly resembling obsessive-compulsive disorder or tourette's syndrome).

Your excitatory neurotransmitters are likely out of whack as well, but really the best thing you can do is eat healthy, follow a schedule, and sleep at a scheduled time for no more and no less than 7-9 hours, and your central nervous system, if at all damaged, will repair itself given the chance to and with the resources needed to (nutritous food and a healthy amount of sleep).

Can atypical antipsychotics inverse dopamine sensitivity?

From what I've read and heard 10+ years ago and haven't heard anything different, they cause pre-synaptic dopamine vesicles to 'pre-load' with dopamine, to be released more frequently than normal, which is likely the cause of 'tics' after a person quits taking anti-psychotics, as the dopamine antagonist is no longer there to dampen dopaminergic activity, and excessive and/or unnecessary action potentials result.

 

They really are unpleasant and terrible medicines; they end up producing neurological and psychological disturbances and long-lasting disorders (I've heard some people say that their 'tics' never went away after being prescribed certain antipsychotics).

The 3 types of schizophrenia diagnosed (paranoid type, disorganized thinking, and catatonic type) are mistakable for behavior caused by stress or trauma. Pronounced symptoms such as 'clanging' / word salad mentioned in literature from the past seems to indicate exposure to neurotoxic compounds (lead, volatile solvents, paints, glue, etc.) which were more common in past decades, rather than wholly attributable to psychosis. Supporting this is the fact that diagnosis of schizophrenia has dropped sharply in modern times, and used to serve as a 'one disorder to lump all cognitive disorders under.

[tkadm30]

I found this study relevant to my OP: https://www.ncbi.nlm.nih.gov/pubmed/25735995