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Many antipsychotics are actually delirants - why on earth are they still used!?

dopamimetic said:
Yeah, this is exactly what we need all over the world, together with some completely new drugs like sigma & kappa antagonists, 5-HT2A inverse agonists and subtype-selective serotonergics in general, more selective glutamate modulators etc ... (not to forget about the real possibility of opioid agonists that lack tolerance development & respiratory depression) !! :)

Why are there so few creative, innovative people at the crucial positions!?
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All of the drugs you listed have been through clinical trials and they all failed as antipsychotics. There are so many novel drugs that have failed -- it's amazing and quite disappointing. mGlu2 agonists, 5-HT2A antagonists, glycine, D-cycloserine, pomaglumetad, bitopertin, volinaserin, ACP-104, AM-831... All of these drugs, and many more, were found to be ineffective in recent clinical trials. I really don't get why you think there are not creative, innovative people working on this problem? Unfortunately, it turns out to be extremely difficult to discover new classes of antipsychotics.

The only exception has been pimavanserin for Parkinson's psychosis. But that is a special case, because the visual hallucinations in those patients occur due to 5-HT2A supersensitivity. But again, it shows people have been trying to find new drugs.
 
Granted, I have to read up more about these clinical trials you've mentioned, this is indeed interesting and disappointing if they all did not work.

But this is independent from the fact that if we'd try the currently approved antipsychotics, they very probably would fail ridiculously too because of horrible side effects and/or being ineffective. And the current practice of psychiatry is blatantly ignoring human rights every day.

I don't say the researchers are not innovative at all. These recent findings and studies are truly amazing and it gives me hope to see that all this excellent work gets actually done despite all the political and capitalistic shit going on. I'm talking about the average doctors, psychiatry care people and all that.
 
dopamimetic said:
Granted, I have to read up more about these clinical trials you've mentioned, this is indeed interesting and disappointing if they all did not work.

But this is independent from the fact that if we'd try the currently approved antipsychotics, they very probably would fail ridiculously too because of horrible side effects and/or being ineffective. And the current practice of psychiatry is blatantly ignoring human rights every day.

I don't say the researchers are not innovative at all. These recent findings and studies are truly amazing and it gives me hope to see that all this excellent work gets actually done despite all the political and capitalistic shit going on. I'm talking about the average doctors
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What you wrote above is completely untrue. For a new antipsychotic to be approved, you have to run at least one trial head-to-head against an existing antipsychotic medication. So there is ample opportunity to re-examine the effectiveness of existing treatments. Plus, and more importantly, psychiatrists wouldn't continue to prescribe drugs if they found them to be inneffective. There are plenty of other antipsychotics and prescribing rates of inactive ones would end up being very low.

Regarding "average doctors" what else are they supposed to do besides prescribing the medications that are approved and available to them?. I get that you have had bad experiences with antipsychotics, but you seem to be missing the point that they are actually helping many people. In fact, there was a poster above who seems to be better off because they are available. There will always be a certain segment of the population that is intolerant or unresponsive to a therapeutic class. Even if a new class was developed, you still might not like it any better. There isn't some conspiracy to cause side effects in patients by blocking new drugs, its just that it is incredibly difficult to block the symptoms of psychosis.

If there is anyone you should be mad at, then it is probably the FDA. Many drug companies have tried to develop adjunctive antipsychotics, which are drugs that could be added to existing antipsychotics to improve their efficacy, thereby lowering the dose of the antipsychotic and reducing side-effects. Unfortunately, under FDA regs, the drug combination must be MORE effective than existing treatments. This ends up being an impossibly high bar -- it is possible to discover effective adjunctive medications that reduce the side-effects of antipsychotics, but it has proven impossible to find a combination that is MORE effective than existing treatments (which are pretty effective against positive symptoms).
 
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I don't say it's a conspiracy at all - I don't believe in the usual theories, they are too obvious and most can also been disproved easily.

There is real benefit from the currently used antipsychotics of course. But I think really we need to differentiate more, there's a lack of empathy and innovation in everyday practice, so many people could improve if they had more open-minded doctors with more time and less pressure, stigma and all that.

It is a hard reality that (nearly) no one will discontinue antipsychotics if they don't make the delusions go away, but force the people to continue taking them or even add other meds on top of them. Also the practice of unlimited maintenance dosing is just plainly wrong, people should get carefully titrated off in a good setting to see if they need the meds at all ... and at last, my point about anti-excitatory medications / anticonvulsants remains ;)

Edit: Yeah, I fully agree that the restrictions for approval of new drugs are too strict and too expensive in many countries.
 
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All I know is that the generic olanzapine I got was no where near as good as the name brand. You know, if you take a name brand Zyprexa and break it in half, the oxygen in the air will immediately turn the white center yellow! But yeah, I do have a degree in chemistry and stuff so it might be surprising to know that I believe that there is a difference. But all sorts of people believe all sorts of weird things, both logical and illogical, and no one can stop them!
 
These drugs are used because they produce effects of use in people with psychosis.

Sure, they are chemical straightjackets. But they're better than real ones.

The deleriant action of the drugs only appears at higher doses, not used in clinical practice.
 
Not to get off topic but I was under the impression that generics were allowed to have a certain amount of variance in their strength from the brand name, I do know that many people absolutely swear that some generics of Ambien and such are horrible.

Anyways, I hope some of these cholinergic medications get somewhere, they seem to help in PCP/Ketamine models of schizophrenia, and it seems that some of the benefit of D3 antagonism might be due to cholinergic efflux.
 
I have always maintained that any differences in generics are due to mental effects entirely. I've seen instances where you can give the same person the same drug, but tell them it's different, and they get different effects.

Tablets have been manufactured for HOW LONG now? You'd think we would be able to measure out milligram dosages accurately... I mean, all other sorts of industries do it OK?
 
Cotcha Yankinov said:
Not to get off topic but I was under the impression that generics were allowed to have a certain amount of variance in their strength from the brand name, I do know that many people absolutely swear that some generics of Ambien and such are horrible.

Anyways, I hope some of these cholinergic medications get somewhere, they seem to help in PCP/Ketamine models of schizophrenia, and it seems that some of the benefit of D3 antagonism might be due to cholinergic efflux.
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I take generic Ambien (zolpidem tartrate) and I've never really experienced any noticeable difference.
 
sekio said:
These drugs are used because they produce effects of use in people with psychosis.

Sure, they are chemical straightjackets. But they're better than real ones.

The deleriant action of the drugs only appears at higher doses, not used in clinical practice.
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Hey sekio,

Yes, I would rather take my pills than live a life of alienation and extreme distress. I know that this is arguing semantics a bit, but I think that there is more to antipsychotics than just inhibiting emotions. One's family and friends may find the individual who's recently been medicated as having less emotion, and so on. But I think that with time, the medication helps the individual grow into a more competent, mature, even altruistic character than if they hadn't been medicated. You've probably heard that the full effect of antipsychotics can oftentimes not be seen until six months after first taking it--time for the social growth that the anitpsychotic enables.

Again, semantics, but a "chemical straightjacket" can be applied to most drugs. What people seem to miss is that the straightjacket starts loose and tightens over time as one continually abuses drugs, and begins very snug yet loosens with time as one consistently engages in their recovery. That's my take, anyways.

And yes, I agree that one would have to take a whole lot of an antipsychotic before any hallucinogenic effect can be realized. They would sooner pass out.
 
I think the benefit of antipsychotics is you can vary the drugs and dosages. In this day and age there are more than a dozen antipsychotics, back in the 50s there were only a few with awful side effects. Straight jackets only come in one size: too tight.

In an ideal situation, modern drugs can and do control the symptoms of schizophrenia or bipolar to the point where they can function in society as individuals with minimal support. That's pretty close to Biblical for people who would have ended up in an asylum neglected only 100 years ago.

It's really a game of finding out what will be best for an individual. Right now it's just a guessing game, but maybe in the future we can use epigenetics or something to figure out which medicines will respond best.

I've had Haldol 5mg IM before when I ended up in the hopsital. That was not fun, let me tell you. Then again I am pretty mentally healthy, and that's a lot of haldol for anyone.
 
Yes and we are aware that as low a dose as possible of an antipsychotic coupled with therapy leads to better outcomes than a very high dose.

Haldol and Prolixin are still used somewhat. I was on Haldol for a couple months (the shot, as at the time I was in danger of noncompliance). I was also given an optional oral dose, along with optional cogentin. Call me crazy (no pun intended) but I actually liked taking the extra haldol and cogentin to just annhilate everything. I think somehow I learned that lack of emotion is much more safe than a surplus of it, for both myself and those around me.

Semantics again. Regardless, there are certain associations that the human mind has the capacity to create that can only result in pain.

I agree. People were astounded. And many many thousands were able to integrate back into society. Sometimes I do wonder though. This brings up a lot of questions. But would I be happier being constantly doped up on barbiturates (as I believe was the practice of dealing with severe mental illness) and not having to expend much effort, or does more happiness ultimately come from fighting against the disease on a daily basis, but living a more typical human existence (socializing, exploring, learning)? In the short term it's almost always the former, but I'm a firm believer that true happiness can never be found in a drug, but is based on social connection. That starts with not deviating far away from social norms.

Support has to be strong and comprehensive for at least years.

To an extent. But I do know that, for instance, Haldol works particularly well against aggression.

Some people take 40mg of Haldol a day.

But as you implied, the answer to the topic question is pretty similar. Functionally speaking, if we didn't use antipsychotics, the "Welfare State" would take on a whole new meaning.
 
Olanzapine:
Common (1% to 10% ): auditory hallucination, restlessness, abnormal thinking, personality disorder

Quetiapine:
Psychiatric side effects have included psychosis, hallucinations, paranoid reactions, delusions, manic reaction, depersonalization, catatonic reaction, emotional lability, suicide attempt, and euphoria

Clozapine:
Common (1% to 10% ): Disturbed sleep/nightmares, agitation, confusion
Postmarketing reports: Obsessive compulsive symptoms, post-discontinuation cholinergic rebound adverse reactions

Chlorpromazine:
Psychiatric side effects including psychotic symptoms, excitability, and reversible catatonic states have been reported. There may also be rare paradoxical psychiatric effects with chlorpromazine therapy.

Chlorprothixene:
Seems to be rare in the US, but it's frequently used in Europe and has acute delirium listed as common psychiatric side effect limiting it's efficacy because it can't be used in high dosages (despite that, I know of use up to several hundred milligrams!) or in the elderly especially.)

Haloperidol:
Less common: hallucinations (seeing or hearing things that are not there)

Risperidone:
More common: Aggressive behaviour, agitation, anxiety. difficulty concentrating or speaking, inability to move the eyes, memory problems. Okay, this one does not seem to share the ability for worsening psychosis. Fits with that it doesn't antagonise muscarinic receptors.
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Granted, I'm probably looking 'too much' at the dark side of all that and there's a great deal of people who get enormous relief from these meds. But it is a hard fact that we have far too much 'collateral damage', non-responders, people with atypical genetics, hyper sensitive ones in combination with exhausted, stressed professionals who have no time or resources or will for empathy and a very rigid system and much of that could be avoided. I've met too many of these to still count every personal fate. Maybe it's once again my overly sensitive shit that's just driving me crazy because I usually 'feel' straight on if someone's really suffering or if he/she's just playing tricks ... I have high respect for the people working every day in psychiatry etc. and are able to do good work every day (but only these who really try to do their best and not have lost their ideals and are just doing it for the money, not caring about the people..) I wouldn't be able to cope with that.

And I think we all agree more or less that side effects, especially the psychiatric ones, tend to be a bit under-reported. Look at the incidence of SSRI discontinuation syndrome for example, they still list it with 1-10% but I'd say every second person will get it after longer treatment.

But I'd still say that quite some of the non-responders could well benefit from being switched off the traditional meds gradually and having some unconventional ones tried! Something unfortunately seems to be quite prohibited in many places because of the doctors having to fear of consequences if they are innovative / creative.

Low doses of haloperidol have been associated with improvement on cognitive test performance in patients in the early stages of schizophrenia.
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<-- this might confirm my theory about haloperidol & maybe sigma receptors, that it indeed could be better than it's reputation when used very very carefully at low, potentially sub-neuroleptic, dosages because it seems to 'irreversibly' inactivate the sigma receptors, like e.g. a MAOI, so this would sum up over time avoiding the acute adverse effects of dopaminergic blockade.

:)
 
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There's no evidence that antipsycotics help drug enduced psychosis

You come out of it naturally

And the joke is the professionals then want you on the poison long term

A nice earner for the pharmaceutical industry
 
I'd have to read up a bit more about that special topic, because I strongly think that especially drug induced psychosis might be a special case that's a tad different from the usual schizophrenia (partly, depending if one has the underlying genetics and drugs actually triggered a 'true' episode, or if it's real drug induced - in the latter case antipsychotics tend to make things worse probably, especially those with anticholinergic effects and using anti-excitatory agents / sedatives together with empathy and care would be a better thing ...)

Low dosages of the non-anticholinergic ones seem to indeed help some people, like Dresden. But they get prescribed too often and too soon in too high dosages as well as for too many diagnoses. People who are depressed mainly and have e.g. paranoid thinking just as a minor symptom definitely should not get on antipsychotics on the first run.

Also there is a definite link between some forms of delusions or drug-induced psychosis, (less stimulant related but from the psychedelics and dissociatives) spiritual experiences and partial epileptic activity, especially temporal lobe lability. These people should not get on antipsychotics because they tend to overall lower the seizure threshold.

But another point I'd be wary of is that when using them over too long time, they can and do 're-wire' the dopaminergic system and produce rebound symptoms, potentially tardive dyskinesia and this could lead to prolonged unnecessary use of these agents. Physical addiction to antipsychotics if you want so. (Seen this in some cases personally.)

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Oh, and about the generics - this is really the power of placebo if you ask me. Especially mental conditions are truly unpredictable and every time one gets them is different than the last occurrence. Even generic ambien from India is exactly the same as the brand drug - I can confirm this. Just the fillers, colours etc. are different (with retard formulae this becomes a bit more complicated, I really think osmotic systems like used with Concerta should become more common).

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And I'm truly curious over what you think about that dopamine -> homovanillic acid -> oxoloacetate promoting / NADPH oxidase inhibiting -> glutamate scavenging & inflammation / oxidative stress alleviating theorising because the underlying research is really new, just from 2014 or 2015 if I'm right and things like NAC seem to confirm it. :)

Would somewhat make sense that individuals who are sensitive to stress have then less dopamine released, less pleasure, motivation -> more stress, more glutamate excitation going on and eventually leading to a state not too far away from stimulant psychosis (or GABAergic withdrawal, to a lesser extent, which also somewhat resembles psychosis from time to time)? PCP/ketamine psychosis seems to result from similar mechanisms (but actually involving dopamine too, not depletion of it, don't know - possibly both, as at least with ketamine it's more a thing of chronic than acute use) at last.
 
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^I had a generic Indian diazepam that felt quite weak in comparison to Valium (which I customarily took) itself. I'd imagine the actual consituents of the pills differ, just not the active compound, so perhaps its differing rate of digestion, absorption and therefore onset time, etc. that causes what feels like a marked difference in experience. Plus, the placebo effect...
 
These Indian drugs weren't the best example probably because there are actually quite a few fakes circulating (specially from online pharmacies) that have less or no of the substance in them. But the generic zolpidem (and others from Sun Pharma) I had was alright.

The point about the constituents is true of course.
 
Risperidone has been called an acetylcholine release promoting agent.

Could anyone explain how that would work ?
 
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