[exmadscientist]

Hey, discussion of orexin receptor stuff! As someone with clinically-diagnosed insomnia, I've been lucky enough to/unfortunate enough to have to try the orexin receptor antagonist sleep aids for a while. As recent, on-patent drugs, they are very, very expensive ($360/month was the number marked on the receipt slip, not that that means much in the US; I certainly wasn't paying that)... and they work. They really, really do work. I was prescribed them because I tried every single other class of sleep aid on the market and they were mostly ineffective, had massive side effects, or were benzos (temazepam: best sleep of my life, but better not use it for longer than a month!).

This stuff? Orexin receptor antagonists? They work. Holy crap, do they ever work. Sleep quality better than the Z-drugs, great tolerability, no massive disruption going off them... when these things go off-patent they're going to be massive. Sleep quality was not perfect (maybe 80% of "normal"? I don't know) but that is absolutely minor compared to the alternative.

(And for the record, I'm off them now due to other stuff clearing up such that I don't need this level of sleep assistance anymore. Not because I can't afford them.)

I guess that's a long-winded way to say that if you're going to do questionably-advised sleep biohacking, orexin receptors are probably the place to start.

[rsyring]

> As recent, on-patent drugs, they are very, very expensive ($360/month...

Expensive is always relative to one's income. But, to put that number into perspective relative to another medication given for a good night's sleep:

I'm the parent of a narcoleptic. The meds to get a good night's sleep, Xyrem, are in the $15k / month range. The recently approved generics are 1/2 that.

[raducu]

> Xyrem, are in the $15k.

Xyrem is basically GHB? A 500 ml bottle of GBL used to be what, 50 euros?

I know the medication is pharmeceutical grade, but are these people insane?

[juliusgeo]

Xyrem is just the brand name for GHB. The company that currently owns the rights (Jazz Pharmaceuticals) pled guilty to felony misbranding in 2011, and in 2013 raised the price by 841%. More recently, in 2017, they sued multiple other companies attempting to produce generics, before settling on an exclusive licensing agreement with one of them. Ironically the headline on their website is "Improving Patients' Lives", but I imagine they aren't reducing the price because Xyrem makes up 74% of total sales [1]. The entire thing reeks of PE--tons of acquisitions.

[1] https://en.wikipedia.org/wiki/Jazz_Pharmaceuticals

[zkelvin]

How long have you been taking them? I've heard that an almost universal side effect is terrifying night paralysis on occasion. Have you experienced that yet?

[thelastparadise]

Yeah, this is is true. I've been taking for 3 months now --best consistent sleep of my life, but definitely occasionally the most terrifying sleep paralysis I've ever experienced, or even heard of.

I know it sounds ridiculous, but ~1-2 nights of absolute terror per week is totally worth it compared to how it used to be (getting maybe ~1 good night of sleep every couple weeks.)

[cj]

Is it intended to be used daily or do you get the “only use very sparingly” advice typical of prescription sleep aids?

[currymj]

website marketing materials for Quviviq make a big deal that it should be used daily for best results.

[exmadscientist]

I did not experience night paralysis while using lemborexant.

I can think of a few reasons I might have avoided it, but who knows for sure. I wasn't on it that long (about a year? not going to look it up), I as a general rule do not remember my dreams unless I'm interrupted, the underlying cause of my total insomnia was pharmalogical, I've always had some level of sleep disorder, I've been on every other sort of sleep aid, I used it with melatonin... who really knows.

[gavinray]

I've been prescribed both available Orexin antagonists (Daridorexant and Suvorexant) for insomnia.

They work very well for me and I've noticed no side effects.

I've been taking them about 2-3 years now.

FWIW, I found Dayvigo to work better than Quviviq but they both do the job.

[0xDEAFBEAD]

>(And for the record, I'm off them now due to other stuff clearing up such that I don't need this level of sleep assistance anymore. Not because I can't afford them.)

If it was available over the counter for, say, $50/month -- do you think you would be taking it just for the improved sleep quality?

Also, what was the specific name of the drug you had such a good experience with?

[smallnix]

Afaiu exmadscientist said their sleep quality improved in the context of their condition, but still worse than a healthy person's sleep:

> Sleep quality was not perfect (maybe 80% of "normal"? I don't know)

[exmadscientist]

Yes, it was noticably lower quality than "good normal sleep" (80%?). Better than I got on eszopiclone (60%?) or zolpidem (40%??), worse than trazodone (90+%, but woke up every day like I'd been hit in the head with a frying pan) or temazepam (150%! amazing! but tolerance within a month and then addiction soon after if one is stupid enough to push back on a benzo, so no good).

[jlpom]

For me they significantly increase REM, it seems at the cost of slow wave sleep. (this is logical as orexin agonism prevent REM sleep)

[comboy]

Have tried/responded to modafinil? It's supposed to also impact orexin pathways.