13 ms·

Evidence of a nocebo response following a nationwide antidepressant drug switch

153 points by EndXA 7y ago

50656E6973 7y ago
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.
arkades 7y ago
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.
- mikehall314 7y ago
  This is also my take on this paper. It records an increase in reported side effects, which is not the same thing as an actual increase in side effects. Patients may have been experiencing these side effects anyway, but either didn’t report them, or didn’t associate them with the intervention. Knowing these side effects are associated with the intervention would likely be enough for Confirmation Bias to increase the reported instance.
- nqzero 7y ago
  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 7y ago
    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.
kitchenkarma 7y ago
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.
- dangrossman 7y ago
  You're commenting on such an investigation. As for the try-and-evaluate method of matching antidepressants to patients, that is the best medicine has to offer right now. There's not a better way that they're choosing not to use, and the drugs do have measurable, significant benefits for patients once they find one or more that's effective for them. The "supposed chemical imbalance is not being measured" because that's more a figure of speech than a scientific theory, and there is no practical way to measure it and correlate it to mood imbalance, depression or other symptoms. What alternative do you propose?
  - seieste 7y ago
    Until recently, few pharmaceutical companies pre-registered antidepressant trials, which allowed them to selectively publish. This means that antidepressants may be nowhere near as effective as commonly believed, and so doctors are overweighting the benefits compared to the costs of side effects. . “While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/ If this is true, then many people who currently take antidepressants may actually be better, not worse, without them, since at least they’d avoid the side effects. Further, the “chemical imbalance” theory that is propagated through paid advertising has no applicability to a doctor prescribing an antidepressant, since the doctor has no way of measuring and monitoring that imbalance should one exist.
beowulfe 7y ago
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-patients-and-providers/update-bupropion-hydrochloride-extended-release-300-mg-bioequivalence-studies https://www.fda.gov/drugs/postmarket-drug-safety-information... I wonder how many patients had their complaints written off for the six years the generic was on the market?
- dontknowme 7y ago
  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.
- nerdponx 7y ago
  I wonder how many patients had their complaints written off for the six years the generic was on the market? Or who didn't even bother reporting their complaints in the first place.
HillaryBriss 7y ago
> ...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?
- deleted 7y ago
  [deleted]
- stordoff 7y ago
  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.science https://www.theguardian.com/science/2004/apr/15/badscience.s...
darkmarmot 7y ago
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"...
rhizome 7y ago
Where have I been that I'm apparently the only person in this thread who doesn't already know what "nocebo" means?
- LeoPanthera 7y ago
  It's the negative equivalent of a placebo. It usually manifests by patients experiencing the listed side-effects of a drug, even when given a placebo.
- stu_k 7y ago
  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 7y ago
    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.
prison-pills 7y ago
Some people do not want an antidepressant. Some people would rather lead a normal, waking life that is not depressing.
sandra101 7y ago
My ex ruined my credit due to his incessant extravagant spending spree, I found myself in a big mess. I talked to a credit repair company and I was told that it would take me non less than a year to fix my credit. I was devastated, that's a very long time which I can't cope with. I looked online and came across Neo's contact, took the bold step of messaging him even though I was skeptical about the whole thing and to my greatest surprise, my credit was repaired 3 working days, my credit was restored from 337 -710. Tbh I was shocked and it didn't cost me too much. I advise you to contact him on (neogonzalezhacks at g mail dot com )for all credit issues, he replies quickly and you can text him on +1 773 688 9662 .
Lazare 7y ago
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.
Lazare 7y ago
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-investigates-pharmac-switches-epilepsy-drug-against-medsafe-advice https://www.rnz.co.nz/news/in-depth/390615/guyon-espiner-inv... 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-research-projects/ https://www.pharmac.govt.nz/news/oia-response-2018-12-12-res... 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.

153 points by EndXA 7y ago

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.

arkades 7y ago

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.

mikehall314 7y ago
This is also my take on this paper. It records an increase in reported side effects, which is not the same thing as an actual increase in side effects. Patients may have been experiencing these side effects anyway, but either didn’t report them, or didn’t associate them with the intervention. Knowing these side effects are associated with the intervention would likely be enough for Confirmation Bias to increase the reported instance.
nqzero 7y ago
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 7y ago
  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.

kitchenkarma 7y ago

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.

dangrossman 7y ago
You're commenting on such an investigation. As for the try-and-evaluate method of matching antidepressants to patients, that is the best medicine has to offer right now. There's not a better way that they're choosing not to use, and the drugs do have measurable, significant benefits for patients once they find one or more that's effective for them. The "supposed chemical imbalance is not being measured" because that's more a figure of speech than a scientific theory, and there is no practical way to measure it and correlate it to mood imbalance, depression or other symptoms. What alternative do you propose?
- seieste 7y ago
  Until recently, few pharmaceutical companies pre-registered antidepressant trials, which allowed them to selectively publish. This means that antidepressants may be nowhere near as effective as commonly believed, and so doctors are overweighting the benefits compared to the costs of side effects. . “While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/ If this is true, then many people who currently take antidepressants may actually be better, not worse, without them, since at least they’d avoid the side effects. Further, the “chemical imbalance” theory that is propagated through paid advertising has no applicability to a doctor prescribing an antidepressant, since the doctor has no way of measuring and monitoring that imbalance should one exist.

beowulfe 7y ago

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-patients-and-providers/update-bupropion-hydrochloride-extended-release-300-mg-bioequivalence-studies https://www.fda.gov/drugs/postmarket-drug-safety-information... I wonder how many patients had their complaints written off for the six years the generic was on the market?

dontknowme 7y ago
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.
nerdponx 7y ago
I wonder how many patients had their complaints written off for the six years the generic was on the market? Or who didn't even bother reporting their complaints in the first place.

HillaryBriss 7y ago

> ...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?

deleted 7y ago
[deleted]
stordoff 7y ago
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.science https://www.theguardian.com/science/2004/apr/15/badscience.s...

darkmarmot 7y ago

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"...

rhizome 7y ago

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

LeoPanthera 7y ago
It's the negative equivalent of a placebo. It usually manifests by patients experiencing the listed side-effects of a drug, even when given a placebo.
stu_k 7y ago
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 7y ago
  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.

prison-pills 7y ago

Some people do not want an antidepressant. Some people would rather lead a normal, waking life that is not depressing.

sandra101 7y ago

My ex ruined my credit due to his incessant extravagant spending spree, I found myself in a big mess. I talked to a credit repair company and I was told that it would take me non less than a year to fix my credit. I was devastated, that's a very long time which I can't cope with. I looked online and came across Neo's contact, took the bold step of messaging him even though I was skeptical about the whole thing and to my greatest surprise, my credit was repaired 3 working days, my credit was restored from 337 -710. Tbh I was shocked and it didn't cost me too much. I advise you to contact him on (neogonzalezhacks at g mail dot com )for all credit issues, he replies quickly and you can text him on +1 773 688 9662 .

Lazare 7y ago

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.

Lazare 7y ago

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-investigates-pharmac-switches-epilepsy-drug-against-medsafe-advice https://www.rnz.co.nz/news/in-depth/390615/guyon-espiner-inv... 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-research-projects/ https://www.pharmac.govt.nz/news/oia-response-2018-12-12-res... 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.