
The antidepressant reboxetine: A headdesk moment in science - J3L2404
http://www.scientificamerican.com/blog/post.cfm?id=the-antidepressant-reboxetine-a-hea-2010-11-30
======
bugsy
Well 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
This 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.

~~~
dkarl
_the 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
A bit of a nit, but once you distort a result, I think you lose the right to
call yourself a scientist.

~~~
dkarl
And yet they will look like scientists to us unless and until someone happens
to shine a light on them. Something to keep in mind.

------
gruseom
Since 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/antidepressa...](http://www.huffingtonpost.com/irving-kirsch-
phd/antidepressants-the-emper_b_442205.html)

(Apologies for linking to huffpo, but the article is by the guy who did the
definitive survey of the research.)

~~~
Alex3917
In 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
I'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>

~~~
Alex3917
Good call. His blog is also phenomenal, but it would probably be difficult to
fully understand unless you've read his book first.

------
pyre
Questions 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.

~~~
hartror
> _Can/should we be testing anti-depressants on animals at all?_

Would you prefer we test these things on humans? Scientists must put
everything pass an ethics committee, testing on animals isn't ideal but the
alternatives are far worse.

I have a vegetarian friend who works on vaccines, he doesn't like it but every
now and again he injects a couple of hundred mice with something and a period
of time later does them in for testing. He does it for the greater good, and
it is done as humanly as possible.

This whole thing has been done to death (pardon the pun) and there isn't an
alternative. If we want to save human lives we have to accept sometimes some
small furry creature is going to lose it's squeak.

Cosmetics on the other hand . . .

> _Is it possible that depression in animals is different than depression in
> humans?_

Mentioned in the article that the tests on animal models of depression need
re-evaluating.

> _Is it possible that lab conditions affect the psychology of the animal?_

See above.

~~~
bioh42_2
_Would you prefer we test these things on humans?_

Yes. I would prefer we test all drugs on humans as soon as volunteers can be
found and the researcher thinks it would be beneficial.

I am assuming a volunteer free from political or even financial pressure,
doing it out of desire to help. And possessing great and detailed knowledge of
the side effects and both the known and potential dangers. I admit this is a
bit of a straw man.

There are two reasons I want this.

1\. Political. I am a libertarian and and thus think that if an adult wants to
jump off a bridge they should be fully within their right to do that. The same
goes if they want to test completely unproven or even fully known to be unsafe
drugs.

2\. Practical. This would speed up research tremendously, it would speed
things up by years. We would save more lives.

~~~
amalcon
_And possessing great and detailed knowledge of the side effects and both the
known and potential dangers._

How, precisely, would you propose that the participants in the first ever test
of a drug obtain such knowledge?

~~~
bioh42_2
Just assume there is a 99.9999% chance it will kill you. Many people would
still take the chance to make a difference.

------
angusgr
Tests referred to in the article:

Forced Swimming Test <http://en.wikipedia.org/wiki/Behavioural_despair_test>

Tail Suspension Test
[http://www.stoeltingco.com/stoelting/productlist13c.aspx?cat...](http://www.stoeltingco.com/stoelting/productlist13c.aspx?catid=2592&home=physio)

~~~
gruseom
I 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
Indeed,

 _"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"...

------
srean
This 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
Antidepressants 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.

~~~
joe_the_user
This 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>

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.

~~~
ZoFreX
Seconding the sentiments on withdrawal. I went off Citalopram cold turkey due
to an incompetent doctor (who incidentally had not informed me that it was a
dependency forming drug). I have never, ever felt that shit in my entire life,
and hope I never do again.

If you ever launch into a profanity-laden tirade at the top of your lungs in
public because a car was inching forwards at a red light, you might also be
going through withdrawal.

Tip for those who want to avoid this: Fluoxetine. Switch to it before
quitting, it has a really long half-life so you can just stop taking it, and
the levels in your body slowly tail off. Much nicer.

------
Estragon
Reboxetine never helped me with depression, but I excelled on the forced-swim
test after my doctor prescribed it for me.

~~~
ars
You'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
There 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
Perhaps 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.

------
dan00
I 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.

------
srean
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.

~~~
Semiapies
How 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
I 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
The 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
I 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.

------
bitwize
Fuck 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.

------
j_baker
> 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>

------
leppie
I 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.

