An Iron Curtain Has Descended Upon Psychopharmacology

http://slatestarcodex.com/2014/08/16/an-iron-curtain-has-descended-upon-psychopharmacology/

by yummyfajitas • 12 years ago

171 99 12 years ago

narrator• 12 years ago

Even out of patent drugs that have effective off label uses get ignored.

TeMPOraL6• 12 years ago

This is one of my favourite blogs I read. There are many interesting and thought-provoking things there, and the author's style of reasoning makes me regain faith that there is still some level of sanity to be found on this planet.

carbocation2• 12 years ago

The original article says the curtain has descended on Psychopharmacology, which seems an important distinction vs Pharmacology used in the submission here.

jamesash• 12 years ago

Yes, when I read the title I was expecting the article to talk about Alexander Shulgin.

fabian2k2• 12 years ago

The analogies with room temperature superconductors and antigravity suggest that bromantane is some kind of super drug. But the only thing the author bases this on is the summary of a study in russian that the author can't even read.

monochr2• 12 years ago

Believe it or not there is a respectable number of scientists, physicists no less, who make a living doing nothing but bringing 80 year old Soviet Science to the west.

Every so often they get the front pages of nature for essentially finding anti-gravity: http://www.nature.com/news/2008/012345/full/news.2008.1185.h...

Or you find actually build computer architectures and languages which American theoretical computer scientists rediscovered 30 years later as the most efficient possible: https://en.wikipedia.org/wiki/Setun

pinkyand• 12 years ago

I have great appreciation for russian technology, but aren't those exaggeration ?

If setun , the ternary computer was so efficient - how is ithat today we use binary machines(and that in general the russians didn't have a moore's law ) ?

StuffMaster• 12 years ago

One of the many disadvantages of a closed state...

TeMPOraL6• 12 years ago

But the only thing the author bases this on is the summary of a study in russian that the author can't even read.

Not true. He said that "they seem to have pretty good evidential support", and that russian study was used only as an example. Also while comparison tu room temperature superconductivity might be a hyperbole, apparently drug having "both stimulant and anti-anxiety properties" that "millions of Russians have been using for decades and are by and large still alive" is something really big in the field of medicine.

fabian2k2• 12 years ago

The possible evidence is in those other journal articles, but they are in russian as well, which the author admittedly can't read. So I'm wondering how he arrived at his conclusion when all the possibly hard evidence is in a language he doesn't understand?

leonth9• 12 years ago

Imagine that there were no FDA Iron Curtain and doctors prescribed afobazole because "the paper was good" (or more likely because the money was good). Then people taking this drug got hospitalized left and right (or - shudder - found dead) because of side effects.

FDA could not do anything to protect her dear US citizens. She couldn't sue the manufacturer or ask them to do further research or impose black box warning or pull the drug out of the market because it was simply beyond their jurisdiction. Doing any of that would constitute a version of the Iron Curtain.

So FDA is doing the right thing to prevent this from even happening by requiring the manufacturer to have everything in place before the drug sees the market.

Furthermore, a randomized controlled trial is no synonym of "drug is good to use". Do they work on US populations? How big is the sample size? Is the methodology sound? What is the side effect profile? Is there any long-term data (like 1 year after using the drug)? These are answered for FDA-approved drugs, but not necessarily for non-approved ones, especially if you are not a healthcare professional that speak Russian (even then, they have teams of professionals looking at drug applications, are you sure you're not overlooking anything?).

a8da6b0c91d3• 12 years ago

The primary issue here is extremely well understood drugs for which the patent opportunity has expired. The only problem is profit incentive, not any serious question marks about safety or efficacy. There are European drugs in wide use for decades with reams of great research that nobody is ever going to bother pushing through approval in America because ultimately no profit would be made.

leonth9• 12 years ago

But the argument still stands, right? Who will be responsible if the "extremely well-understood drugs" have some problems in the US? They don't care about US population because it is such a small market for them. Let's say we lower teh barrier of entry by waiving these "extremely well-understood drugs" from proper research in US. There are instances of drugs that exhibit different side effect profile due to genetics in different population, and this sometimes tip off the risk-to-benefit balance, how do you account for that?

The more barrier you place for drug approval, the safer it will be. It is a classical risk-versus-benefit trade-off. If there is an option that may be slightly more effective than current practice but has unknown (or perceived less certain) side effect profile, healthcare industry mindset prefers the status quo.

"First, do no harm." http://en.wikipedia.org/wiki/Primum_non_nocere

davmre2• 12 years ago

You're right that the solution shouldn't be automatic US approval for any drug used in Russia. It's reasonable to have standards for drug testing and require that any drug used in the US is tested to those standards.

The problem isn't (only) that US drug standards are strict. The problem is that the financial burden of testing a new drug, which is significant, lies solely on the manufacturer, who can only recoup those costs by selling patented drugs at high prices. This means that the incentives don't line up for drugs not covered by US patents: because there's no profit in selling them, no manufacturer can justify funding the clinical trials to get them approved. This despite the fact that society would, as a whole, benefit from having those studies done.

One obvious solution would be a government program whose mission is to identify promising treatments for which private incentives don't line up, and shepherd them through the approval process by funding clinical trials and so on. You could also imagine a free-market variant, in which the government just auctions off US patent rights for foreign drugs; the auction winner gets exclusive rights to sell the drug in the US for some limited period of time in exchange for agreeing to fund FDA approval.

leonth9• 12 years ago

One obvious solution would be a government program whose mission is to identify promising treatments for which private incentives don't line up, and shepherd them through the approval process by funding clinical trials and so on

You already have this. It's called Orphan Drugs in the US. http://en.wikipedia.org/wiki/Orphan_drug

a free-market variant, in which the government just auctions off US patent rights for foreign drugs

This will probably work. But once the barrier is too low, a lot of "useless" drugs will show up (i.e. providing more choices to prescribers but in reality does not really give much benefit) - and you need to fund those too using the taxpayers' money.

Retric2• 12 years ago

You can get a patent for 'novel' treatments for existing drugs which should in theory fix this issue.

JoeAltmaier3• 12 years ago

Overthinking it. The Russian regulations presumably are adequate to protect her own citizens; its not necessary for US sufferers to sue in Russia to correct manufacturing problems there.

Its hubris, American regulatory groups sticking their fingers in the affairs of other countries. And its beyond their charter to try to regulate what Americans do; they're supposed to regulate what American manufacturers do, not private citizens?

tptacek• 12 years ago

The author is talking about a market category in which successful drugs are worth billions. If these Russian drugs are so effective, why isn't some pharma firm in the US driving them through testing? The answer can't be "because the FDA is capricious and rejects drugs at the last minute", because that problem applies to all drug research, and we obviously have a lot of drug research.

leonth9• 12 years ago

The answer may be one of:

* US pharma is developing a me-too / copycat drug that has very similar molecular structure

* US pharma has tried and it failed before public announcement (oh there are so many of them)

* US pharma negotiated contract and found that the Russians are non-negotiable :)

FBT• 12 years ago

But we have patents, as well. If a major US drug company invents a new superdrug, and spend decades and billions of dollars to get it approved, they can at least be sure that if it gets approved they will get the royalties from its sale.

But if a company spends decades and billions of dollars fighting for the approval of a drug they do not hold the patent on, they are by no means guaranteed making even a single penny of that investment back, even in the best case scenario where it succeeds in getting through the FDA.s

JoeAltmaier3• 12 years ago

Hyperbole. Marketing is how the rest of us sell things. Giant drug company would have many advantages there. They are likely to sell boatloads of product regardless of patents. The patent is a greedy attempt to dominate the market legally in addition to commercially by creating a monopoly.

shabble• 12 years ago

Successful drugs, or successful drugs that are eligible for patent protection? I imagine[1] it would be much harder to turn a profit on the massive upfront costs if you immediately had to compete with the existing manufacturers at generic-scale prices.

It seems like it might be useful (assuming it isn't already) to separate the rights concerning drug discovery and those demonstrating efficacy/safety to allow costs to be recovered.

Then again, it needs to be weighed against the inevitable rent-seeking that pharma has a name for.

[1] but don't have any evidence handy to back it up, so ICBW.

eliben• 12 years ago

Isn't this the normal case of drugs having different names in different countries? I thought this is why the drugs also have a secondary, chemical, name that describes the actual molecules. Even the most popular drugs have different names - Tylenol isn't named like that in Europe or Russia, AFAIK.

bronbron• 12 years ago

It doesn’t count if some foreign scientists already did a bunch of studies. It doesn’t count if millions of Russians have been using the drug for decades and are by and large still alive.

Um, no, it doesn't. What's the FDA going to do if they have additional questions or want additional studies done?

The FDA doesn't approve these drugs for the exact same reason the author doesn't prescribe them.

Lament the situation, sure, but pointing fingers at the FDA seems dumb.

drcode2• 12 years ago

The author doesn't prescribe them because they don't want to get sued.

The fda doesn't allow them because they are (argues the author) run by big pharma.

TeMPOraL6• 12 years ago

The fda doesn't allow them because they are (argues the author) run by big pharma.

The author argues that "big pharma" doesn't seek the FDA approval because there's no way to recoup the expense.

To quote,

"Absent an extremely strong patent on the drug there’s no reason a drug company would want to go forward with all of this. I don’t know what the legalities of buying Russian drug rights from Russian companies are, but I expect they’re complicated and that pharmaceutical companies have made a reasoned decision not to bother."

Note the reasoned decision part. The author's actual point is summarized in the N-2th paragraph:

Everyone follows their own incentives perfectly, and as a result the system as a whole does something insane. Classic multipolar trap..

chimeracoder• 12 years ago

This was the state of HIV medications twenty years ago - the first medications were available in other countries, but not yet in the US. The movie Dallas Buyer's Club depicts this period of history excellently.

lafar6502• 12 years ago

Do you really think America needs more psychoactive drugs?

tim3332• 12 years ago

Maybe the FDAs mandate could be changed to regulate drugs to maximise the benefit to society. That way things like Melatoin should be allowed and the shenanigans detailed in Bad Pharma (book by Ben Goldacre) should be dealt with. There seems a lot of stuff that is not entirely in the public interest at the moment.

drcode2• 12 years ago

Yes, regulation is always improved by additional regulation.

TeMPOraL6• 12 years ago

Unless you can prove that applying additional regulation always leads to bad outcomes, you need to prove that in this case it will before rejecting OP's idea off-hand.

tim3332• 12 years ago

I was thinking more changing the priorities rather than more.

lilsunnybee3• 12 years ago

Melatonin is already easily and cheaply available on any pharmacy or grocery store shelf in the US. Regulation of many older drugs still classed as 'supplements' is in fact very lax.

treekiller2• 12 years ago

so is this article about drugs, presumably a complex molecule involving many elements, or actual new chemical elements?

TeMPOraL6• 12 years ago

About drugs that work well, are deployed around the world and US has no equivalent of, that somehow still don't get imported to America.

Symmetry4• 12 years ago

It's important to look at the FDA's job in terms of diminishing returns, or maybe as a classification problem. You have some number of drugs coming in, some of which are helpful and some of which are harmful. But you don't have any perfect means of figuring out whether a drug is good or bad. If you start from no screening it's very easy to stop a lot of bad drugs without stopping many good drugs, but as you apply tighter and tighter criteria the ration of good drugs you accidentally stop for each bad drug you stop gets higher and higher.[1]

In practice, of course, some of the rejected drugs aren't explicitly rejected by the FDA but rather rejected by the system because they are never put through the FDA screening in the first place, but the principle is the same.

One would ideally want to set the difficulty of getting through FDA testing to maximize some quantity, such as the average effect of an approved drug on people's Quality Adjusted Life Years. But it's clear that this is not actually what happens. When the FDA rejects a drug people never hear about the lives that were not saved by it, but if even a single person is killed by a drug that was let through FDA screening. Every study on the matter that I've seen says that the FDA is actually way too restrictive in how it regulates drugs. And I should mention that this is in contrast to other countries such as most of Europe or Canada or Japan which have much saner drug regulation regimes.

I should also say that this is only a criticism of the FDA in it's role as a drug regulator. It seems to do a pretty good job as a food regulator. I suppose the number of voters involved in food production dwarfs those involved in drug production.

[1] You get more type 1 errors for each type 2 error. http://en.wikipedia.org/wiki/Type_I_and_type_II_errors

refurb6• 12 years ago

You have to keep in mind the history of the FDA. When kids were being born around the world with flippers instead of arms and legs because of thalidomide, that wasn't happening in the US because of the FDA. Incidents like that breed cautiousness.

The pendulum swings back and forth. A decade ago, the FDA got hammered for being too cautious. Then Vioxx happened and they got hammered for being to lenient. I think the FDA does a dam good job to be honest. Mistakes are made, but I'd give them an A- overall.

The other thing to keep in mind is that the US has pretty lenient "supplement" regulations. As long as you can prove it's safe and don't make efficacy claims you can't backup the FDA will often leave you alone. I'm often amazed at what the FDA allows regular citizens to buy.

Symmetry4• 12 years ago

I'll admit that on average the FDA has gotten better over the last few decades. They are genuinely better than when they caused 10,000 excess deaths a year for a decade due to their refusal to permit beta blockers during the period they were in use in other countries. But you can't say "Both Type 1 and Type 2 errors are occuring, so they must be balanced."

dmm• 12 years ago

Thalidomide was very effective in treating morning sickness, it "just" wasn't safe. Why does the danger of thalidomide justify giving the FDA extensive powers to regulate the effectiveness of treatments?

cdr2• 12 years ago

You can't attribute thalidomide being blocked in the US to "the FDA". Frances Oldham Kelsey was practically solely responsible for stalling the drug until sufficient evidence of birth defects emerged to reject it. She was under intense pressure from within the FDA to approve it. In addition, the US benefited from being the last major market to receive the drug - if it had been developed in the US, the US would have almost certainly been hit just as badly as Europe.

The scandal did lead to FDA drug testing reforms, but that was after the fact.

(Also, there were US victims of thalidomide birth defects. There were human clinical trials and the American distributor aggressively distributed "free samples" to employees.)

cbsmith2• 12 years ago

To say the least, the problems with the FDA are pretty well documented: http://www.nap.edu/catalog.php?record_id=11750#toc

cbsmith2• 12 years ago

And I should mention that this is in contrast to other countries such as most of Europe or Canada or Japan which have much saner drug regulation regimes.

Except for example, Canada tends to just accept whatever the FDA accepts.

treekiller2• 12 years ago

Author seems confused as to the naming of chemical elements. Just because the Russians might use different names for elements doesn't mean they have discovered chemically unique elements.

http://en.wikipedia.org/wiki/List_of_chemical_elements_namin...

sgt101• 12 years ago

The first bit of the article is an analogy to highlight the bizarre situation described in the second bit.

leonth9• 12 years ago

I'm not sure about US law, but there should be a provision like importing a non-licensed drug for a named patient, with declaration from the doctor and pharmacist saying that they bear full responsibility in case anything goes bad. Using this the doctor can import any kind of drug as they wish - but of course they must be responsible for it as there is no more "screening" from FDA.

Singapore has this provision because the market is too small for lots of drugs to come in.

davorak• 12 years ago

Singapore has this provision because the market is too small for lots of drugs to come in.

Interesting how do doctors end up bearing "full responsibility"? It seems like something has to work differently in civil court or current culture most be different enough that the doctor is not run out of business after a few patients die after importing and taking responsibility for a drug.

leonth9• 12 years ago

Singapore is not really as litigious a society as US, I don't think there is ever a case where the patient sues the doctor because s/he uses an exemption (non-registered) drug. In some cases the patient probably doesn't even know that the drug is not registered.

Importing a drug under exemption is "serious business" and is usually only done by the most senior doctors (or by approval from a committee of senior doctors). They must exhaust all registered options first before moving to exemption drugs, and the pharmacists play a role in ensuring that (another incentive to do that is the paperwork can be rather significant).

Because you need a pharmacist to do this, it usually happens only in larger establishments like hospitals, where pharmacists are readily available and cooperative.

refurb6• 12 years ago

That kind of already exists. US resident are allowed to import up to 90 days worth of a prescription drug. For drugs that aren't prescription-only, the FDA doesn't really care unless they feel the drugs are unsafe.

Most of the drugs mentioned in the article can be purchased by people in the US through the internet.

jotm2• 12 years ago

I'm more worried about the fact that more and more drugs are reclassified as prescription only. Right now, I can only get green tea or alcohol without a prescription for anxiety - not exactly the best choices.

No Adderall, Xanax or Provigil for me either - the only things I can get right now are Tofranil from a friend (which is technically illegal) and racetams from eBay.

KC8ZKF3• 12 years ago

Why can't you see a doctor about your anxiety?

mindslight2• 12 years ago

Why should he have to?

jotm2• 12 years ago

I'm abroad most of the time. Sure, I could go see a local doctor, but it would be much easier if I could just get the medication I need (and know to be working based on previous prescription) instead of wasting time and practically begging a doctor for those specific pills.

From experience, shrinks will prescribe whatever they want instead of what I ask for, since they know better and I'm a dumb foreigner who can't even explain things properly.

lilsunnybee3• 12 years ago

I understand Xanax, but why Adderall and Provigil? Both of those are stimulants, and if anything they would only increase the anxious tension you are already feeling. Maybe you meant Ativan? Not sure about the modafinil though.

Are you dealing with EDS as a significant symptom in addition to anxiety? ADHD?

acr25• 12 years ago

The analogies in this article are stretched to the point of nonusefulness and the sarcasm makes it difficult to parse what the author is saying.

slyrus• 12 years ago

I think the problem here is that the predictive value of the "pretty good evidential" support and success in a future (acceptable to the FDA) clinical trial isn't as high as you might think.

Admittedly it's for a different indication, but the Medivation experience with dimebon, which is a drug used in Russia as an antihistamine for decades, which had "pretty good evidential support" that the drug might work for Alzheimer's disease is, unfortunately, more likely to be par for the course.

atmosx2• 12 years ago

I study pharmacy in CZ. I know about the categories mentioned and the drugs any US (or western-based) Doctor should know, but also never heard about the Russian drugs that are mentioned.

Very eye-opening article. I remember coming in contact with the Chinese pharmaceutical/medical system through a discussion with a our Chinese guide. After the discussion I was left with the impression that Chinese medicine is still in the dark ages and for some reason doesn't wanna join the 21st century. Then our "History of Pharmacy" teacher let me know that Chinese medicine is as good as ours although their approach is strange to us, works extremely well for them hence there even might be many things worth to copy there. I still remember how stunned I was.

atmosx2• 12 years ago

The problem lies in the so called social contract each society wants to endorse. Either people face drugs as social goods (social economical model) or as goods (liberal model).

If drugs are social goods then, in theory you put the well being of the masses above anything else.

If drugs are just goods to be marketed, then there's no need to bother. Either the financial aspect is lucrative (e.g. reasoned) or you can't have legal access to the drug.

ps. The fact that the US has the worst and most expensive health system in the world of course, says something about healthcare.

caycep• 12 years ago

"Different elements" is a hard sell on this post, because aren't they sequentially increasing protons, neutrons, etc? How can you not have elements on one periodic table vs another?

guelo• 12 years ago

The solution is to have a public pharma: someone, maybe the NIH, that takes unpatentable, unprofitable drugs through the FDA process.

lilsunnybee3• 12 years ago

That would involve maintaining healthy research funding levels, rather than continually making cuts.

lnanek2• 12 years ago

It is considered novel having both stimulant and anti-anxiety properties.

That would be handy. I did take an American anti-anxiety drug for a short while during a painful divorce, but I went from someone who gets hours of work done on the bus to work every day to someone who just stares out the window. Sure, I was happy and not worried and not desperate, but I wasn't getting half the amount of work done either.

perrylaj• 12 years ago

I've had a similar experience with anti-anxiety medications. While they (benzos in particular) do alleviate the 'synergistic cycle of worry/negative thought' I associate with anxiety, that isn't necessarily beneficial in the long-term. At times I feel like low levels of anxiety are almost behaviorally indistinguishable from 'initiative to do un-preferred stuff I should be doing'. If anxiety is triggered by (or a barrier to) not accomplishing things you should, or feel you should, taking such medications could be counter-productive.

But a medication that disrupts the anxious cycles of thought while at the same time stimulating the motivation/energy to complete tasks... well, that sounds almost like magic to me, especially if it doesn't involve the retrograde amnesia associated with benzos like alprazolam, lorazepam, etc.

lutusp4• 12 years ago

I can't believe the linked article never says, "Eventually we'll know what these conditions are in a biological sense, after which this debate about drugs will go away, replaced by actual science, in which a drug either does or does not address an established, known cause."

So long as we administer drugs based only on their effect on symptoms but without understanding root causes, there will be all kinds of abuse and fads.

bayesianhorse3• 12 years ago

God forbid we should use treatments that could reduce suffering in patients...

lutusp4• 12 years ago

Like recovered memory therapy, for example, or prefrontal lobotomy? There's a reason mainstream medicine forbids therapies that have no experimental verification, a wise practice that has yet to take hold in psychology.

asdfologist2• 12 years ago

This is most likely an extremely unpopular opinion here, but mandatory FDA approval is another one of those government regulations that I think the world would probably be better without.

If I'm desperate for medicine and am willing to take a risk by taking a non government-tested drug, then shouldn't that be my right? Also, it's not even entirely clear whether on the whole, the FDA saves more lives than it harms. Sure, it's prevented many bad drugs from going to market, but the astronomical costs (both time/money/energy) associated with getting drugs approved by the FDA 1) slows down good pharma companies and 2) discourages many people from starting good pharma businesses at all.

A free market solution to this would be to have FDA and/or commercial enterprises vet the drugs with open, transparent standards, and the pharma companies can choose at will whether or not they want to be certified by these companies (and list whatever certifications they received on their products). The consumers can then choose at will whether they want to buy products with only these certification(s), or they can take a gamble and buy completely uncertified products.

Entrusting a government agency to retain totalitarian, opaque control over what drugs can make it to the market is just a bad idea.

stefantalpalaru• 12 years ago

Not long ago, the free market solution was snake oil. Literally.

asdfologist2• 12 years ago

And it should be my right to buy snake oil, just as it is my right to pay hundreds of thousands of dollars for Scientology courses.

Grue3• 12 years ago

A lot of these Russia-specific drugs are scams. The papers glorifying their magical properties have no scientific basis, but rather published for bribes. There are serious papers in Russian medical journals describing healing properties of holy water. There are very popular anti-flu drugs like Arbidol that actually do nothing. This is the country where pseudoscience reigns supreme.

An Iron Curtain Has Descended Upon Psychopharmacology

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