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The antidepressant reboxetine: A headdesk moment in science
- srean 16y agoIneffective modification of an existing drug as a means of extending the validity of a patent is a widespread practice. This was possibly not the case here. But given that we are tolerant of such practices and defend them, it comes as no surprise to me that an established drug on the market has no effect on the symptom that it was meant to address.
- nopassrecover 16y agoWell the article discusses a different issue - the drug passes objective animal-based anti-depression tests with flying colours but, for an unknown reason, is ineffective on people. This raises the question of how we should objectively measure anti-depression efficacy.
- srean 16y agoThats not the full story though. The article mentions that the manufacturers were aware of the fact that it was ineffective on humans and hid that data. Discrepancy in animal and human efficacy isnt new by any means, thats why drugs go through a protracted human tests.
- Semiapies 16y agoHow does it follow that questionable patents derived by making small changes to existing drugs leads to drugs that have no effect? I think that's begging the question.
- srean 16y agoI think you got me wrong. I didnt say that questionable patents lead to drugs that have no effect. Infact if you read it again you will find that I explicitly pointed to that possible misinterpretation. My point was that in an environment where it is possible to extend the duration of a patent by adding modifications to the parent molecule that are known to have no benefit, it does not surprise me that a marketed drug has no benefit either. My point was about my lack of surprise, not a cause and effect relation.
- Semiapies 16y agoThe entirety of your comment: "Ineffective modification of an existing drug as a means of extending the validity of a patent is a widespread practice. This was possibly not the case here. But given that we are tolerant of such practices and defend them, it comes as no surprise to me that an established drug on the market has no effect on the symptom that it was meant to address." I only see your explicit admission that the first situation (questionable patents derived by making small changes to existing drugs) might not even apply in this case. You do not "point" to a "possible interpretation", you were breezily suggesting a lazy and fallacious connection. Privileges granted that you disagree with are a different matter than scientific dishonesty. We could remove the whole issue of chemical-tweak patents on drugs by allowing perpetual drug patents, or by ruling that new drugs must be chemically different to some particular degree to not be covered by a patent (expired or not), or by abolishing drug patents entirely, and none of those solutions would imply anything as to the efficacy of future drugs or the trustworthiness of drug research.
- srean 16y agoI still dont see where I made the connection that you ascribe to me. Nevertheless if such a connection is indeed visible in my comments, thats probably my lack of native english skills showing. Suspecting that my comment might be misinterpreted, I attemped to prempt that. Apparently not very effectively. So let me try again: We are tolerant of, or inadequately vigilant of ineffective drugs. One such sign can be seen in a particular apect of the patent system I described. Given this environment, it does not surprise me that a particular drug was found to be ineffective. Your downvotes came with an explanation, which is better than silent downvotes.
- pyre 16y agoQuestions I don't see being asked: * Can/should we be testing anti-depressants on animals at all? * Is it possible that depression in animals is different than depression in humans? (i.e. animal tests are useless) * Is it possible that lab conditions affect the psychology of the animal? (i.e. who won't be depressed spending your life in a cage, especially for larger animals like chimps, but also for social animals like rats which are undoubtedly caged individually) Some of these are fundamental questions that call into question the validity of any tests, yet it seems like the community in question is more concerned with 'finding the right tests' within a framework that they assume to be correct.
- nopassrecover 16y agoI got the impression that the scientifically-relevant (e.g. non-ethical) questions you list would be asked. Having said that, the community should be more concerned with 'finding the right tests' - our "safe" method of testing drugs we suspect are okay is animal testing (whether that is ethically right or wrong), and animals are probably easier to test objectively in this situation, as well as possibly immune to the placebo effect.
- pyre 16y agoI'm under the impression that questions like: "Is it possible that lab conditions affect the psychology of the animal?" aren't asked because: * No one wants to know the answer if it means that we no longer have a test framework to experiment within. If tomorrow we found out that we couldn't use animals as test subjects because the validity of any such experiments was suspect, then how would 'we' generate grant money? * Hand-wavy answers like, "It's impossible to know, so we'll just assume that the answer is no."
- hartror 16y agoWrong! Those are exactly the questions that are asked. The tests use a group of control subjects vs test subjects which is standard throughout science. This means it takes out a factor such as what environment the animal is stored in by simply storing them all in the same type of environment. This is done every time a study is run to remove minor variations. Science is all about controlling the variables, it is actually what scientists spend most of their time thinking about. What really went wrong in this case is when they got to the point of testing humans they stopped doing "science" and started doing "business". If they hadn't sweeped the bad data under the rug they could have published a lovely paper about how the standard tests for depression in animal models failed (in reboxetine's case, one goat a herd does not make, the tests could just be bad for reboxetine for some reason).
- bugsy 16y agoWell all they did is discard all the results that showed it didn't work in order to make billions in profit while causing life threatening side effects. No harm, no foul. Not as bad as that guy Wakefield, who mentioned that one of the patients had an odd formed head, but didn't make enough of a deal about it.
- hartror 16y agoThis isn't being taken lightly as you seem to imply, the scientists responsible for this are a bit screwed career wise. Wakefield got more attention because of the massive damaging effect he and his ilk had on immunization rates.
- j_baker 16y agoAssuming the scientists were responsible. Perhaps it's possible some of the business types blocked some of the reports?
- joe_the_user 16y agoThe scientists were at least responsible for letting the reports be blocked.
- dkarl 16y agothe scientists responsible for this are a bit screwed career wise What, the companies they worked for are just going to hang them out to dry? Not likely, not if they want scientists to keep distorting results for them. The scientists responsible for this might not have the admiration of their peers, but they'll be securely employed.
- spiffworks 16y agoA bit of a nit, but once you distort a result, I think you lose the right to call yourself a scientist.
- angusgr 16y agoTests referred to in the article: Forced Swimming Test http://en.wikipedia.org/wiki/Behavioural_despair_test http://en.wikipedia.org/wiki/Behavioural_despair_test Tail Suspension Test http://www.stoeltingco.com/stoelting/productlist13c.aspx?catid=2592&home=physio http://www.stoeltingco.com/stoelting/productlist13c.aspx?cat...
- angusgr 16y agoAlthough I know it's not at all -literally- why they are used (not to mention that they may not work), these tests seem to say something to me about our understanding of depression, right there.
- redthrowaway 16y agoIt's kind of hard to ask a rat if he's feeling blue. While I agree that the tests are somewhat suspect, they're used because they provide an objective metric that isn't influenced by experimenter bias. We'll likely need to find something else that will work better. In the end, I agree with you, but I'll add this: I think this is a triumphant moment for science. We ran tests, we thought we were getting one result, but we got another. Now, we'll reexamine our assumptions, and attack the problem with renewed vigor. The end result will be a much greater, and much better founded knowledge of depression. I love that science always wins. Even, and especially, when it fails.
- gruseom 16y agoI can't help feeling that there must be ways for us to find our way in this world without torturing other living things.
- joe_the_user 16y agoIndeed, "Wait, and ponder how there is noting quite so cute as a mouse swimming..." It seems a little disturbing that the model for which drugs humans should receive should be "how well does it make animals seem to perform when we torture them"...
- leppie 16y agoI think I was prescribed Edronax in 1999 for a very short while. The side-effect was knocking me out and caused me to sleep for 20 hours a day... I stopped very soon with them.
- srean 16y agoThis is not directly related to the post. But gauging that this topic will attract readers knowledgable about antidepressants, I figured I might get an illuminating response. I often read that a side-effect of a antidepressant is heightened suicidal feelings. That completely mystifies me. Isnt it exactly what it is supposed to be working against ?
- forensic 16y agoAntidepressants motivate people to improve their lives. One obvious way to do this is suicide. If your every moment of existence is painful, suicide is an immediate improvement. It's the motivational aspect that seems to increase suicide - motivation turns people's lethargic depression into a more active form of depression where they find the will to carry out their desires. A common desire among the depressed is the desire for death. Your typical depressed person however is too depressed to even exert the energy or thinking necessary to end his life.
- srean 16y agoAh! it makes more sense now. Thanks
- joe_the_user 16y agoThis may be one explanation of the phenomena but there are others. For example, some anti-depressants disrupt REM sleep, creating a phenomena akin to a waking dream and thus making individuals less sensitive to finality of their actions. http://en.wikipedia.org/wiki/Antidepressant#REM_Sleep http://en.wikipedia.org/wiki/Antidepressant#REM_Sleep Also, the most dangerous time for suicide for a person on anti-depressant is when they suddenly stop taking them - as happened to a good friend of mine. It is hardly the motivational quality that gets people going at that point. Edit: suicidal AND homicidal feelings are "rare" but all-too-common responses to anti-depressants and especially to withdrawal from anti-depressants. I've had friends who had both responses in fashions that are at least very unexpected. Anyone with loved-ones taking such drugs, be on your guard.
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- Estragon 16y agoReboxetine never helped me with depression, but I excelled on the forced-swim test after my doctor prescribed it for me.
- ars 16y agoYou're joking - but that's actually an EXTREMELY interesting question. Would humans on Reboxetine do better on a forced swim test? Because if they do, but they are still depressed then that's clear evidence that the forced swim test is worthless. On the other hand if it has no effect, then humans are different from animals and don't react the same way to drugs, but the test may still be good.
- JonnieCache 16y agoThere is no way you could ever do a forced swim test on a human. You would be sent to prison for a long time. You'll have to go back to the earlier half of the 20th century to see research like that.
- sorbus 16y agoPerhaps not a forced swim test, but having a human swim in place (or tread water) for as long as they can. In a swimming pool, with people around to rescue them if they stop swimming and start drowning, and being removed as soon as they give up by ... I don't know, going over and grabbing the edge of the pool? Or making some unambiguous hand gesture, or yelling a safe word, or whatever. I'm not entirely sure how valid the results from this would be, but there's also controversy over forced swim tests with rats and mice, so it would probably be just as accurate.
- ars 16y agoThe test doesn't measure swimming, but rather how long before they give up. So you could make a rigged test. For example: Tell people you will pay them $200 if they can find the exit of a maze (either real or on the computer). But the maze is rigged, and has no exit. Then time how long it takes before they give up.
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- j_baker 16y ago> Whereas drugs like citalopram and fluoxetine primarily target the neurotransmitter serotonin, reboxetine targets the neurotransmitter norepinephrine. I'm curious if this might be effective as an ADHD drug. This is essentially what Strattera does: http://en.wikipedia.org/wiki/Atomoxetine http://en.wikipedia.org/wiki/Atomoxetine
- gruseom 16y agoSince no one else has mentioned it: it's not just this antidepressant whose effects have been (at best) exaggerated, but pretty much all of them. http://www.huffingtonpost.com/irving-kirsch-phd/antidepressants-the-emper_b_442205.html http://www.huffingtonpost.com/irving-kirsch-phd/antidepressa... (Apologies for linking to huffpo, but the article is by the guy who did the definitive survey of the research.)
- Alex3917 16y agoIn addition to Kirsch's book, I'd also recommend Anatomy of an Epidemic. It does a really good job explaining the biological reasons why SSRI's can't work. (Plus it also outlines all of the different reasons why the science behind them is fraudulent, same as Kirsch.)
- MaxGabriel 16y agoI'll recommend Whitaker's book, too. You can check out some of the original scientific studies he cites on his website, though it of course makes more sense with his context http://robertwhitaker.org/robertwhitaker.org/Depression.html http://robertwhitaker.org/robertwhitaker.org/Depression.html
- Alex3917 16y agoGood call. His blog is also phenomenal, but it would probably be difficult to fully understand unless you've read his book first.
- chopsueyar 16y agoThis all seems like GameGenie for your brain, where big pharma enters random codes. http://en.wikipedia.org/wiki/Game_genie http://en.wikipedia.org/wiki/Game_genie
- dan00 16y agoI have experience with all kinds of antidepressants, targeting serotonin, dopamin and norepinephrine. The norepinephrine one isn't directly changing my mood, or reducing my fears, but it's definetly increasing my drive, in a kind waking me up. Perhaps my depression isn't "typical", because it seems mostly originating from an affection of the pituitary.
- bitwize 16y agoFuck antidepressants. I was on 'em, and I went off 'em of my own volition because I knew they didn't bloody work (and made me tired besides). Wanna cure your depression? There are two ways. 1) Change how you think. Most of the time it requires conscious effort on your part, sustained over months or years; although if being poor has you depressed and you win the Powerball, that can give you an instantaneous new outlook. Cognitive behavioral therapy has proven vastly more effective than any drug. 2) The route Bill Zeller took. For some people that's their only way out of misery and suffering, and the rest of us need to learn how to respect their choice on an individual and societal level.