Schizophrenia drugs may have been off target for decades, study finds
1–10 of 131 posts
Re: Schizophrenia drugs may have been off target for decades, study finds
#2Situation normal.
Consider the discovery of valproic acid:
"Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder."
To this day, nobody knows exactly how it works, apart from the fact that it hits more than a few targets. (And it's a particularly potent inhibitor of the epigenetic modulator histone deacetylase.)
Apart from a subset of very clear-cut cases -- steroid hormones, peptide hormones, and certain aggressive chemotherapeutic drugs -- there's no clear model for most small molecule drugs. Even really mundane ones like metformin and paracetemol are very imperfectly understood.
Re: Schizophrenia drugs may have been off target for decades, study finds
#3Link to the actual paper: https://www.nature.com/articles/s41593-023-01390-9
Re: Schizophrenia drugs may have been off target for decades, study finds
#4Re: Schizophrenia drugs may have been off target for decades, study finds
#5The brain is really complicated, and all psychiatric medications affect multiple receptors and subsystems. Framing this study as "antipsychotics were off target" is an editorial choice. The title could just as easily have been "Improved understanding of antipsychotic action means we may be able to design better antipsychotics."
Edit: It also ought to be noted that the study was on mice that had been given amphetamines to mimic psychosis. Which is interesting and good science, but seems far from enough evidence for the press to write stories with headlines like "Everyone Was Wrong About Antipsychotics" or "Schizophrenia Drugs May Have Been Off Target For Decades, Study Finds."
This sort of internet story bothers me because I've spent time around schizophrenics who are recovering from a psychotic episode. Schizophrenia can get really, really bad, in a way that I don't think most people who haven't had contact with the psychiatric medical system understand. Antipsychotics have awful side effects, but for many people the alternative is uncontrolled psychosis, which can be vastly worse.
There's a decent chunk of people who inherently and vocally dislike psychiatric medication, and these media stories are in that tradition. But the only people who ought to be involved in the decision about using antipsychotics are the patient, their family, and their medical providers. Writing headlines that are too broad for the evidence that supports them does not help improve the lives of people with schizophrenia.
Re: Schizophrenia drugs may have been off target for decades, study finds
#6It's amazing how far the medical world has come in treating ailments of the body, but we've made comparatively little headway in ailments of the brain.
Re: Schizophrenia drugs may have been off target for decades, study finds
#7It's amazing how far the medical world has come in treating ailments of the body, but we've made comparatively little headway in ailments of the brain.
If instead of saying brain you say "The most complicated structure found in the known universe so far" it starts to make a little more sense on the enormity of the problem at hand.
Most organs are composed of one or only a few types of cells and their particular arrangement doesn't matter that much. For example swapping kidneys between people doesn't change who they are (mostly, smaller edge conditions apply here). But we can't swap brains because the brain encodes your 'youness'.
Re: Schizophrenia drugs may have been off target for decades, study finds
#8Same study discussed previously:
https://news.ycombinator.com/item?id=37057135
(50 points/3 days ago/51 comments)
Re: Schizophrenia drugs may have been off target for decades, study finds
#9The brain is really complicated, and all psychiatric medications affect multiple receptors and subsystems. Framing this study as "antipsychotics were off target" is an editorial choice. The title could just as easily have been "Improved understanding of antipsychotic action means we may be able to design better antipsychotics." Edit: It also ought to be noted that the study was on mice that had been given amphetamine…
The story could just as easily be "Improved understanding of antipsychotic action means we may be able to design better antipsychotics"
And that would be a more accurate understanding of it - and I hope its true. Current antipsychotics are helpful but imperfect.
Re: Schizophrenia drugs may have been off target for decades, study finds
#10The study used a mouse model where amphetamine is used to simulate schizophrenia. Obviously, it's not guaranteed to map to real humans having real schizophrenia.
That doesn't mean it's a useless result, but everyone should remember that research is an accumulation of decades of many little pieces of information. This is another clue, not a "nail in the coffin" of old theories.
The ultimate evaluation of medication is how well it actually performs in studies. If someone can develop a new medication that is more selective for D1 and show that it performs better and/or has fewer side effects then this would be a great result.
However, don't get too excited. The pharmaceutical industry is often 10 steps ahead of public findings like this. A selective D1/D5 antagonist with negligible D2 affinity has already been trialed for schizophrenia without good results: https://en.wikipedia.org/wiki/Ecopipam
Many of the most prescribed schizophrenia medications already have significant D1 affinity, too, so it's not really correct to say that we're "off target"
These findings tend to be very aggravating to computer scientists who are familiar with systems that (mostly) obey clear-cut rules and can examined in extremely fine detail with enough equipment and motivation. Neuroscience is not so simple, but that doesn't mean it's all wrong. Each finding is one more piece of the puzzle.