Comment by haldujai | Hacker News Reader

Comment by haldujai | Hacker News Reader

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> Do you know what else sounds like a recipe for killing people? Not allowing people to access therapeutics that might save their life because it hasn't yet gone through regulatory approval yet for whatever reason (delays, too expensive to submit), etc.

You're assuming a therapeutic not tested in humans has a better chance of saving someone's life than something tested and available. Do you have any evidence to support this?

> One of the most tragic is amisulpride. Amisulpride is an antipsychotic medication used to treat schizophrenia and other psychiatric conditions. Some key notes about its regulatory status:

There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

This review compared the effects of amisulpride with those of other so called second generation (atypical) antipsychotic drugs. For half of the possible comparisons not a single relevant study could be identified. Based on very limited data there was no difference in efficacy comparing amisulpride with olanzapine and risperidone, but a certain advantage compared with ziprasidone. Amisulpride was associated with less weight gain than risperidone and olanzapine.

What's so tragic about this? Equally efficacious antipsychotics are available. Once again the alternative to non-approved drug isn't nothing or inferior substance.

I will concede that legacy off-patent drugs are part of the "very limited" gap with the FDA, this doesn't hold for new drug discoveries as discussed in the article.

Even then, there is an ongoing US trial for amisulpride and the substance is approved for nausea/vomiting (granted not in oral form).

[0] https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD...

The issue with antipsychotics tends to be the side effects, not the efficacy

Amisulpride, for a lot of people, would be one of the best antipsychotics.

Antipsychotics are incredibly important medications for a lot of people. It really matters that amisulpride is not available.

https://psychnews.psychiatryonline.org/doi/full/10.1176/appi...

"A comprehensive meta-analysis published in 2019 in JAMA that compared 32 oral antipsychotics helped solidify the sentiments shared by Kahn and other investigators who have conducted clinical studies with amisulpride. That meta-analysis identified amisulpride as the second most effective antipsychotic at reducing overall symptoms in schizophrenia patients (behind clozapine) and the most effective in terms of reducing positive symptoms. The analysis also ranked amisulpride better than clozapine in terms of tolerability and side effects."

> Antipsychotics are incredibly important medications for a lot of people.

Agree.

> It really matters that amisulpride is not available.

Not sure about this, I'm not a psychiatric expert but my cursory lit review shows conflicting meta-analysis as to whether amisulpride is better than 2nd gen. Although your source is newer Cochrane is generally the gold-standard on SRs and the included studies in the 2019 JAMA article predate the Cochrane review, they detail the limitations of comparison.

Looking at Canada, amisulpride is limited to special access and is also not first line.

The UK pharmacotherapy guidelines are also waffly and cite limited evidence to guide firs-line decision making.

A systematic-review from China showed different side-effect profile for both, hard to say which is better. Amisulpride was cheaper.

In any case old drugs that were never approved are part of that "very little" I was referring to that fall through the cracks.

Not sure I'd call this one tragic though given that other countries also don't use it or limit access and there are good alternatives.

The problem with "there are similar efficacy rate alternatives" is that, for most psychiatric drugs, it's not necessarily the _same_ population that is helped by two different drugs at similar efficacy for the same issue, even if the total success rates are comparable.

A number of people have tried many different individual or combinations of treatments before finding something workable, or close enough to workable that you can paper over the cracks. I would strongly suggest against concluding the lack of access to something isn't an issue for some patients because they have alternatives, without very compelling evidence.

A story from my recent past - I've had, historically, no issues swapping between different generic manufacturers, or name brand and generic, if someone stopped making something I was taking, or I moved and the pharmacies stocked different versions, or whatever. So a little over a month ago, when I noticed my meds looked visibly different after getting them filled, I checked to be sure they hadn't given me the wrong thing, but no, same dose, different generic manufacturer, and I stopped worrying.

...until I started getting extremely nauseous to the point of being debilitating, for 6-8 hours every time, when I take this medication twice a day. So I went back and tried the third generic manufacturer the pharmacy had, after a few days of making sure it wasn't a fluke, and the third one had the same issue. We finally ended up switching to the extended release version of the med, which had still more different manufacturers, and did not have this issue, since the first manufacturer had a shortage for over a month and counting.

Medications are a lot less interchangeable than we might hope.

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