Given that you have a large stake in your own market, please could you clarify your criteria for 'reputable proof'? Especially if that includes community-generated proof, which is unlikely to be unbiased.

For instance, I think a good level of proof would be 3+ formulations of medicines licensed for ADHD in US/UK/Europe being found by a third party lab, reported in a formal Certificate of Analysis (or equivalent) to be containing ingredients other than stated in the Summary Product Characteristics (UK thing) or other country's equivalent, or the expected ingredients in proportions/quantities other than stated.

This would be a rigorous standard of proof, relatively unbiased, and also easily achievable given the apparent scale of concern here.

@WXTJ In hindsight I think this standard of proof being directly verifiable is unlikely even all standards are met. I would suggest that reporting from reliable (subjective) vaguely mainstream professional journalists of evidence like this would be adequate, and that only one widely available (eg in US only would be fine) ADHD medicine would be adequate.

I also sold my 'no' stake because I saw a story about Pfizer owned company manipulating quality control for an extended release methylphenediate (quillivant XR), to hide that it wasn't dissolving as easily/quickly as it should. It is an XR oral suspension indicated in children (I don't know if it is also licensed for adults, but many are used off label in adults anyway). This is 7-10y ago. FDA were at the time receiving some 'lack of effect' reports about the product which didn't go anywhere (Pfizer said, plausibly, that this related to dose titration).

This is the Reuters story about it. This is the (very long) 'plaintiff's first amended petition' from the court case.

It seems plausible that this would cause a more extended, lower level effect from this drug. But it seems unlikely it would cause no effect. It was also a long time ago so probably unrelated to the currently reported issues. And there is no claim that the active ingredient was not present in the expected amount, and no evidence relating this solubility issue to clinical effects.

I sold my stake because I thought this story might get exaggerated as proof, and there is no good resolution criterion on this market currently.

Every single drug has massive tolerance and reversibility of tolerance. Most stimulants in particular have wildly variable effects.

Amphetamines are pretty famous for their ability to induce nervousness and paranoia, and even caffeine will do this.

You do the math on what happened (leaving aside how suggestible people are)

(bored, wanted to write some)

The physical world has a complexity hierarchy based on distance. Larger, more complex things are built of smaller, simpler things. And molecules are pretty small, and pretty simple, often made of a couple dozen "atoms". There aren't that many distinct configurations available.

So, for the drugs lisdexamfetamine and amphetamine, which are small molecules - there's not a lot of room for variation. Amphetamine has two optical isomers - but not a few thousand! A beam of steel can have hidden structural weaknesses in the arrangement of its molecules, caused by the distribution of temperature when it was formed. A program can have malicious code hidden in a few thousand of its million bytes. A drop of saliva can have literal viruses. A molecule of amphetamine can't. Your amphetamine pill has a certain amount of levoamphetamine, a certain amount of dextroamphetamine, and a bunch of other inactive stuff, binders, flavor, whatever. (er, in theory manufacturers could add other substances along with the standard ingredients, and those could do all sorts of things - but that'd be a much larger breach of ethics/laws/standard practices than '20% less active ingredient' or 'different binder', so I doubt that)

And due to said simiplicity, modern tech (for example) can quickly figure out what sorts of molecules are in something, and how much is present. If a significant amount of Vyvanse didn't have any lisdexamfetamine, that'd be trivially demonstrated, both with cheaper tests and more expensive techniques. And the same is true of 'XX% less inactive ingredient'. If you genuinely think there's been such modification, and can find old and new pills, see if you can convince a friend who can run a lab test. (I don't think it's worth doing though)

Also, the FDA requires testing of manufactured pharmaceuticals, and they're pretty good about it.

What's happening, then? Certainly at least half of it is just placebo and dumb people being dumb, especially the "negatives on drug tests", which is a bit out there.

Is that it? Maybe not - that inactive stuff above could play a role. It easily affects absorption (both amount and rate) of the drug - and different concentrations in the blood over different durations often means different effects. As a result the FDA requires bioequivalence tests for generics, to ensure that, with the new formulation and inactive ingredients, similar amounts are present in the blood for similar durations. But there are all sorts of arguments online that this isn't as good as it should be. I'm not actually sure here - it's possible that, despite that, different generics might have meaningful differences. There are many reports of 'my doctor switched me to a generic and I felt different' - along with some reports of 'my pill stopped working, i couldn't figure out why, until I realized I was switched to a generic, I switched back and it's back to working'. That might play a role, not sure.

One hint is the in-thread anecdote says something's been off for "much longer". If there was a widespread change in ADHD medicine, precipitated by the supply shortage, it'd probably happen around the same time for a large group of people - but people start 'feeling off' at a fairly constant (and non-insigificant) rate.

@jacksonpolack

In terms of not containing the active ingredient, I agree.

ADHD medications made me realize the dosing rate /delivery method really changes the perceived experience and side effects. Taking Ritalin 20mg 3x daily can be experienced differently than 60mg biphentin, and one might cause perceived irritability while the other doesn’t.

Complaints with different delivery methods on generic vs brand name ADHD medications have happened before as listed below. I think the scenario is unlikely, but there’s more complexity than I would have initially expected. Need to consider delivery method and not just measurable drug.

https://www.goodrx.com/concerta/certain-generics-are-no-longer-equivalent-to-brand-name-concerta

https://www.fda.gov/drugs/drug-safety-and-availability/methylphenidate-hydrochloride-extended-release-tablets-generic-concerta-made-mallinckrodt-and-kudco

@jacksonpolack not saying it is the case here, but it is compatible with the timeline of a crystal polymorph kerfufle, which would not necessarily be detected by the usual analytical methods. Though it ought to be detectable by bioequivalence tests, it may be that the polymorph shift is recent, and the test are from before.

https://pubmed.ncbi.nlm.nih.gov/11474792/

For example, the ritonavir polymorph thing took time to take hold, didn't trigger at all plants at the same time.

Anecdotal evidence, but my partner and I (especially my partner) have been noticing that something has felt off with our ADHD medications for much longer than we've known that it's a widespread conspiracy theory. My guess is that if this is true - and I dunno if I'd put odds higher than 60% on that - we might not know definitively for a long time. It would be a massive scandal if it's true, and pharamceutical companies would definitely like to cover it up.

@evergreenemily There seems to be groups of people organizing testing and other investigations. You are right than an official outcome might take years, but I would be willing to resolve yes if there is well created community proof.

There are a lot of confounding factors. People switching medications due to shortages may find the delivery method less effective but that isn’t a conspiracy. But they are potentially lumping in with Vyvanse generic truthers and other miscellaneous complaints to create a wide spread discussion.

It seems like it would be quite possible to resolve the negative testing complaints relatively fast at the very least. Other complaints may be more difficult.

@evergreenemily Occam's razor suggests that your bodies are developing a tolerance to your medication, or that something that's changed in your diet or your environment has made your ADHD medication less effective (I prefer the latter theory, personally - I have read a paper that suggests certain preservatives can affect ADHD symptoms, for example, but I think that it showed correlation not causation).

@evergreenemily what do you say to @RobinGreen's Occam's Razor argument?

@RobinGreen Our diet and environment haven't changed significantly in the past six months or so. My partner has also expressed that one month's supply felt "more like 10 (milligrams) than 30" while the next felt significantly better to them despite no change in the dosage labeled on the bottle.

@evergreenemily @RobinGreen also the complaint isn’t limited to just one couple. Since it’s quite widespread it would have to be something like: 1. real medication alteration 2. Change in dose required due to Covid stressors and environment change. 3. Mass suggestibility. (Or a mix of multiple factors)

ADHD medications aren’t necessarily associated with strong tolerance development and certainly not in a synchronized fashion.

Multiple people report an immediate difference between one bottle of medication and the next

@BrodieFerguson No it would not have to be! It could be due to e.g. increasing air pollution in a given area (Ohio train derailment, anyone!?) or increasing contamination of the water supply in a given area. Even if you get your water in bottles, you could still be affected by water pollution getting into the food chain.