11 Comments
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redbert's avatar

your recalibration therapy idea is cool!

Lauren Cortis's avatar

I've bookmarked this to read again, as I'm still processing it. It makes intuitive sense to me though - persistent sexual dysfunction with SSRIs is one obvious example, but there are many other times in practice where I've encountered situations where pharmacological mechanisms aren't enough to make sense of the clinical picture of side effects. Usually these types of adverse effects either get labelled as 'idiopathic', or dismissed and ignored by the prescriber.

Super interesting post Michael - thank you, I'm thoroughly intrigued and will be thinking about this for some time, I'm sure.

Michael Halassa's avatar

Great! Thanks Lauren. If you have any follow up thoughts I’d love to hear them

Lauren Cortis's avatar

For sure. Being a pharmacovigilence nerd, I can’t resist encouraging you to report this adverse effect on FAERS if you haven’t already. We really know so little about the long term safety of these types of medicines when used ‘in the wild’- ADR reporting is all we’ve got to go by a lot of the time.

Charles Stromeyer IV's avatar

Interesting post. In adults age 16-35, high doses of prescription amphetamine (like Adderall) increased the odds of psychosis or mania by 5X which is also interesting since the biology of mania is not well understood:

https://psychiatryonline.org/doi/10.1176/appi.ajp.20230329

Michael Halassa's avatar

Thanks Charles. This is totally congruent with my sense of what I’ve seen. Awesome info, as always.

Maxwell's avatar

I noticed that clozapine is notably absent from that meta-analysis. Do you think this theory could shed some light on its efficacy in refractory or treatment-resistant psychosis, and, if so, how might that work?

Mykyta Nikitenko's avatar

Interesting way to model delusions during psychosis through the machine learning, but it brings very simplificated fragmented vision on this, because psychosis is much more complex and it is not only about only one symptom (delusions). Conclusion that for this particular woman's case was caused by stimulant medication is just dangerous, people might be afraid to start life saving medications because someone just cherry picked random case and made an incoherent conclusion of this.b

Cam Will's avatar

do you truly agree with this?

DC Reade's avatar

Perhaps there should be more research into the upside of "mania" or "manic states", given that the prodrome is associated--anecdotally but persistently--with a disproportionate amount of invention, innovation, and creativity. Granted, some manic states are psychotic, or lead to the neurotransmitter exhaustion associated with depression. But others have produced some amazing art, literature, craft ingenuity, and scientific advance. Maybe mania stops being a problem--or at least, as much of a problem--if it's channeled into a productive outlet.