
Evidence of a nocebo response following a nationwide antidepressant drug switch - EndXA
https://cpe.psychopen.eu/article/29642/
======
kitchenkarma
I think this should be investigated.The use of anti-depressants amount to
performing medical experiments on people. E.g. Let's see this anti-depressant,
then evaluate side-effects, if it doesn't work switch to different one or
adjust the dosage. There is no scientific basis to do that. The supposed
chemical inbalance is not being measured so the doctors really are giving
people random drugs and those drugs are difficult to quit without medical
supervision as well. When you quitting you feel so horrible you rather keep
taking them. This is a huge money making racket for big pharma and make
doctors look like charlatans at the same time casting doubts on medical
profession. This only feeds to another camp like anti-vaxx.

~~~
javadocmd
Forgive me for being blunt, but that's just how modern medicine works. No one
has the Star Trek tricorder that can scan your body, read your genome, and
detect a quantum fluctuation in your synaptic waveform matriculation to
calculate how many CCs to put in the hypospray.

We really only have one amazing piece of technology at our disposal:
statistics. At the absolute best (and I'm not saying it's always the best...),
what comes out of a pharmaceutical development pipeline is a drug that works
for some people some of the time. Sure, sometimes you get broad categories to
try to narrow down effectiveness, but at the individual level there is
ultimately no choice but to try a drug and see if it works. And this is
especially true in psych drugs, in no small part because there are so many
unanswered questions about how our mind works.

And that sucks. I get it. It must be so frustrating to deal with a revolving
door of new regimens and new side effects, all while yearning for relief from
the underlying ailment. Not to mention navigating our nightmarish medical
bureaucracy. But please understand that doctors, generally, are just doing
their best to help given the tools they have. If you don't currently have that
kind of trust and partnership with your doctor, I hope you are able to find
one with which you can. I wish you the best, and hope that this perspective
will make your frustrations somewhat easier to bear.

~~~
hedvig
Oh all of a sudden we should just accept some pathetically weak argument of
"we just don't know". Billions at stake here and yes we can and will severely
penalize anyone on the side of nonscience and profiteering where humans are
harmed. We can do better. Sorry if it means consequences for certain people.

~~~
PhasmaFelis
> _Oh all of a sudden we should just accept some pathetically weak argument of
> "we just don't know"._

But we _don 't_ know, despite enormous and ongoing effort. Hopefully we'll
understand eventually, but right now we don't. I'm sorry if that fact is
upsetting, but you can't will knowledge into existence.

------
beowulfe
On the other hand, sometimes there are significant differences between generic
and brand name formulations. For example:
[https://www.fda.gov/drugs/postmarket-drug-safety-
information...](https://www.fda.gov/drugs/postmarket-drug-safety-information-
patients-and-providers/update-bupropion-hydrochloride-extended-release-300-mg-
bioequivalence-studies)

I wonder how many patients had their complaints written off for the six years
the generic was on the market?

~~~
dontknowme
Absolutely, even when the active compounds are the same but there are changes
in composition.

For instance, I'm an asthmatic and I need to use a spray inhaler. The no-brand
equivalent is exactly the same, and does work the same in normal
circumstances, except has roughly 1/2 of the propellant. But I can tell you
that the missing propellant makes all the difference when you're having a
stronger attack and cannot inhale.

------
Lazare
I'm a bit sceptical here. As it happens, my partner was taking Effexor (a
branded formulation of venlafaxine) and was switched to the generic Enlafax.
She complained to me that she was feeling a little bit worse starting around
this point, and when patient groups started sharing stories of many people who
began feeling worse following the switch (which is what led, eventually, to
the media coverage), she requested switching back to Effexor (which required
paying out of pocket, as it's no longer covered), resumed taking it, and
started feeling better.

She will no doubt be part of the statistics that paper is using to suggest a
nocebo effect, as she only complained publicly after the media coverage
started, but she has notes showing she had noticed the effect _prior_ to
seeing anyone else complain about the generic formulation.

To be clear: her experience is absolutely not proof that Enlafax is in any way
inferior or different than Effexor (for my partner specifically, or for people
in general)! It's very possible her entire experience was a nocebo effect
(triggered, perhaps, by the Enlafax packaging or something) followed by a
placebo effect when she switched back to the branded drug. However, it _could_
equally have been caused by Enlafax being actively inferior for her.

What I think is fairly clear from my partners experience, however, is that the
study is not correctly designed to reject the null hypothesis here. It's
assuming that the people who publicly complained about Effexor after the media
coverage were fine with it until the media coverage, whereas it's just as
plausible that they simply didn't publicly complain until they realised other
people were also having an issue.

Ultimately, any study here that's not a proper double blind test is going to
struggle pretty hard here, and I think this is no exception.

------
50656E6973
The inverse is also true:

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/)

Just goes to show how powerful the media is at shaping/controlling the
individuals reality.

------
rhizome
Where have I been that I'm apparently the only person in this thread who
doesn't already know what "nocebo" means?

~~~
stu_k
It's in the article:

"These switches to generic medical and psychotropic medications have from time
to time caused an increase in reported adverse events, and this is likely to
be due to negative attitudes towards generic medicines rather than
pharmacological differences between the branded and generic versions of the
medication.

This phenomenon is known as the nocebo effect"

~~~
rhizome
I don't know if I'd call that "in" the article. I suppose it's an explanation
of a sort, but really? It looks like it was spit out by a science-bullshit
generator.

------
Lazare
A bit of backstory:

NZ has socialized medicine, with a central drug buying agency (Pharmac) who
tries to save costs where it can. It also has a drug safety agency (Medsafe).
Not uncommonly, Pharmac reckons they can save money by switching brands, and
Medsafe may raise concerns.

In 2017, Pharmac moved from funding a branded formulation of venlafaxine
(Effexor) to a generic formulation (Enlafax). A lot of patients reported
issues (almost 2k, which is a fair number given the size of the country), and
it was a bit of a black eye for Pharmac. So Pharmac went and paid a researcher
at a local university to study brand switches in general and the 2017
venlafaxine switch in particular, and show (hopefully) that the issues weren't
real, hadn't caused significant problems, and that it was totally fine to
switch psychiatric meds. (Which is relevant _now_ , because Pharmac is looking
at switching another medicine, Medsafe has raised strong concerns ("potential
significant safety issues", "goes against international consensus", etc.), and
Pharmac wants to find a way to move forward while covering their ass in case
it turns out Medsafe is right.)

In any case, the result was this study. It could well be right, but uh, do
keep in mind the context, which is that the researchers got paid hundreds of
thousands of dollars to conduct it by an interested party hoping to save
millions of dollars and fend off accusations that they had harmed people and
risked lives.

Any study funded by people with such a strong interest in it having a specific
outcome that then comes out with the exact outcome should be taken with a
grain of salt. Doubly so when the study omits to disclose that funding!

Local NZ article with a good roundup of the current controversy, the 2017
issues, and the linked study: [https://www.rnz.co.nz/news/in-
depth/390615/guyon-espiner-inv...](https://www.rnz.co.nz/news/in-
depth/390615/guyon-espiner-investigates-pharmac-switches-epilepsy-drug-
against-medsafe-advice)

Note: The article says that Petrie received NZ$400k from Pharmac for the
study. For anyone wondering if that's right, the answer is: Yes! Although it
took the NZ equivalent of a FoI request to find out. See
[https://www.pharmac.govt.nz/news/oia-
response-2018-12-12-res...](https://www.pharmac.govt.nz/news/oia-
response-2018-12-12-research-projects/) And note that the study itself
disclosed nothing about funding. Given that Pharmac has a _very_ strong and
very obvious vested interest in this matter, I find this ethically troubling.

------
darkmarmot
Except they used suicidal thoughts as their key symptom -- which is something
that is widely already known to increase in prevalence with media attention,
see: "13 Reasons Why"...

------
arkades
This article does not show any evidence of a nocebo effect. It shows increased
reporting following publicity - without distinguishing whether the result was
increased incidence of perceived harm, or just increased /reporting/ of
perceived harm (for instance, if patients would not have previously attributed
those somatic symptoms to their medication.)

Crap study, just an excuse for a publication.

~~~
nqzero
agree that it's crap study, but even worse than that it's an attempt to
discredit symptom reporting in general

while talking extensively about the nocebo effect, it ignores the fact that
without media coverage a patient may experience side effects but not connect
that effect with the switch from one drug to another, or may think they're
imagining the effect, etc

~~~
Lazare
Absolutely. My long-term partner was in this exact situation: She _did_
experience some fairly mild side-effects, complained about them to me, but
didn't consider that the medication switch might be the cause until she saw
others complaining, checked, and realised the symptoms had begun at the time
she'd changed meds. She had simply assumed that she wouldn't have been
switched to the generic if it wasn't identical, and thus initially assumed
that any symptoms she was experiencing must be caused by something else; the
exact _opposite_ of what the study claimed, despite the fact that she will
have been counted in that study as evidence of a nocebo effect.

------
HillaryBriss
> _...people report a reduced therapeutic effect and more side effects from a
> generic-labelled placebo compared to a branded placebo_

wa? the power of branding -- advertising can be beneficial?

~~~
stordoff
Lots of things can influence the placebo effect, branding is one of them:

> and we know that two placebo sugar pills have a bigger effect than one, and
> that an intramuscular placebo injection is more effective than a placebo
> sugar tablet[...]

> And a four-way comparison, with either sugar pills or aspirin, in either
> unbranded aspirin boxes or mock-up packaging of the Dispirin brand, showed
> that brand-name packaging, and the wealth of advertising and cultural
> background material that packaging plays on, had almost as big an impact on
> pain as whether the pills had any drug in them. So in some ways, it's not
> irrational to believe that costly Nurofen is more effective than cheap
> unbranded ibuprofen, even if they've both got the same active ingredient.

[https://www.theguardian.com/science/2004/apr/15/badscience.s...](https://www.theguardian.com/science/2004/apr/15/badscience.science)

