4 ms·

Hey, I wrote about monoamine oxidase inhibitors on Scott Aaronson's blog a few months ago: https://www.scottaaronson.com/blog/?p=4933 https://www.scottaaronson.

Hey, I wrote about monoamine oxidase inhibitors on Scott Aaronson's blog a few months ago: https://www.scottaaronson.com/blog/?p=4933 https://www.scottaaronson.com/blog/?p=4933 Basically, there's is an international shortage for one of the most effective treatment for severe depression because of an unfortunate series of events, the drug's long history as a generic and the manufacturers' willingness to replace the drug class, and constantly produce new patented molecules with chemical tricks(ex. just taking one isomer in the citalopram->escitalopram case, or even metabolites in the case of venlafaxine -> desvenlafaxine case) like they are 'annual smartphone model releases', except efficacy even goes down. You can read more about it the drug itself on the blog of Scott Alexander (the rationalist/Bayesian psychiatrist guy) as well: https://slatestarcodex.com/2015/04/30/prescriptions-paradoxes-and-perversities/ https://slatestarcodex.com/2015/04/30/prescriptions-paradoxe... And now some years down the line after his observation, the price has exploded, very few new patients get a prescription due to uncertainty and there's no alternative. Your options are either taking taking an atypical antidepressant like vortioxetine or an experimental ketamine.

caycep 6y ago
selegiline is cheap. Rasagiline is available but I suspect cost inflated. However, I don't think either are targeted at depression, esp at the doses available.
- alphadelta 6y ago
  Those are MAO-B inhibitors; i think the thread was referring to MAO-A inhibitors, which are the mechanism for depression.
  - caycep 6y ago
    I supposed I should have read it more carefully. It refers to phenelzine which is...both. It's nonselective so it's an A and B inhibitor. How good is it, I cannot say as not a lot of people prescribe it anymore. The problem with it is that a risk of hypertensive crisis, especially in combination with tyramine in aged foods, or inducing an overload in combination w/ any other drug that raises monoamine neurotransmitter levels, i.e. SSRI's etc. It's become kind of a bogeyman. So the original source seems to be trying to fight that particular "meme" in medical education. I'm not about to wade into pubmed regarding how often hypertensive crisis happens in a 60 or 70 year old drug, but there may be a point in that as medical students, we memorize the "quick bites" of some of these things as our time and attention is extremely limited in figuring out what to study for the boards. and if we do want to prescribe it, we have a pharmacist pushing back on the other end of the phone because it has this thing as a big scary Black Box Warning on the drug. I will say, MAO-B inhibitors (at least those studied in anti-parkinsonian trials and doses) don't seem to do anything. No hypertensive crisis, but we haven't been able to see a huge therapeutic effect either. The psych people dose them at 6 times the parkinsonian dose though...<shrug> The other potential angle on that post is...this may reflect on some aspect of an unregulated generics market. Aside from phenelzine, I seem to see weird swings in availability and pricing of generics in the past few years.
peteretep 6y ago
> monoamine oxidase inhibitors > citalopram ... venlafaxine God I hate myself for being that guy, but neither of the drugs you’ve listed are actually MAOIs. I’m sure the point still stands though.
- pyentropy 6y ago
  That's exactly the point. The selective classes (SNRI/SSRI) are marketed as a complete and safe replacement for MAOIs, on top of the chemical structure irony. Even the new atypicals with innovative chemical structure (and targets other than 5-HT1/SERT) are of significantly worse efficacy MAOIs I'll edit my parent comment to make it clearer.
  - peteretep 6y ago
    I don’t quite get the point you’re making then, as there’s a lot of generic citralopam on the market, despite escitralopam being patented.

caycep 6y ago

selegiline is cheap. Rasagiline is available but I suspect cost inflated. However, I don't think either are targeted at depression, esp at the doses available.

alphadelta 6y ago
Those are MAO-B inhibitors; i think the thread was referring to MAO-A inhibitors, which are the mechanism for depression.
- caycep 6y ago
  I supposed I should have read it more carefully. It refers to phenelzine which is...both. It's nonselective so it's an A and B inhibitor. How good is it, I cannot say as not a lot of people prescribe it anymore. The problem with it is that a risk of hypertensive crisis, especially in combination with tyramine in aged foods, or inducing an overload in combination w/ any other drug that raises monoamine neurotransmitter levels, i.e. SSRI's etc. It's become kind of a bogeyman. So the original source seems to be trying to fight that particular "meme" in medical education. I'm not about to wade into pubmed regarding how often hypertensive crisis happens in a 60 or 70 year old drug, but there may be a point in that as medical students, we memorize the "quick bites" of some of these things as our time and attention is extremely limited in figuring out what to study for the boards. and if we do want to prescribe it, we have a pharmacist pushing back on the other end of the phone because it has this thing as a big scary Black Box Warning on the drug. I will say, MAO-B inhibitors (at least those studied in anti-parkinsonian trials and doses) don't seem to do anything. No hypertensive crisis, but we haven't been able to see a huge therapeutic effect either. The psych people dose them at 6 times the parkinsonian dose though...<shrug> The other potential angle on that post is...this may reflect on some aspect of an unregulated generics market. Aside from phenelzine, I seem to see weird swings in availability and pricing of generics in the past few years.

peteretep 6y ago

> monoamine oxidase inhibitors > citalopram ... venlafaxine God I hate myself for being that guy, but neither of the drugs you’ve listed are actually MAOIs. I’m sure the point still stands though.

pyentropy 6y ago
That's exactly the point. The selective classes (SNRI/SSRI) are marketed as a complete and safe replacement for MAOIs, on top of the chemical structure irony. Even the new atypicals with innovative chemical structure (and targets other than 5-HT1/SERT) are of significantly worse efficacy MAOIs I'll edit my parent comment to make it clearer.
- peteretep 6y ago
  I don’t quite get the point you’re making then, as there’s a lot of generic citralopam on the market, despite escitralopam being patented.