Jan 22 2009
Through the CAM Looking Glass
A newly published systematic review of a controversial anti-migraine drug, migrostat, shows that it works no better than placebo. The review for the Cochrane Collaboration looked at 33 trials, involving a total of 6,736 patients. Those patients treated with migrostat had a reduction of frequency and severity of migraines of about 30%, but this was no better than the placebo group which experienced a similar reduction (there was a “slight” advantage for tension headaches, likely noise in the randomness) – a response rate typical of placebo treatment for subjective symptoms.
The lead author of the review, Dr. Jacob Bayous, who works for the Pharmaceutical Industry Research Center, is quoted as saying:
“Much of the clinical benefit of migrostat might be due to non-specific effects and powerful placebo effects, meaning selection of specific chemical constituents may be less important than industry proponents have traditionally argued.”
Despite the fact that this review clearly shows that migrostat is no better than placebo – the standard scientific interpretation of which is that it does not work – industry proponents (who are eager to get FDA approval for migrostat) claim that the drug works – “as placebo.” They argue that migraine sufferers still find relief from taking migrostat, and that relief is valuable, even if it is only an effect of the “power of the mind.”
Bayous advocates for further research, saying:
“Doctors need to know how long improvements associated with migrostat will last and whether higher doses of migrostat will achieve better results than lower doses.”
This negative review of migrostat is not the first of its scientific problems. The drug has stalled for years, failing to gain scientific support because it’s “active” ingredient appears to be pharmacologically inert. Evidence suggests it is broken down in the stomach and not absorbed as an intact molecule. In fact, it’s breakdown products are mostly glucose – sugar. It is therefore not surprising that the “drug” is no more effective than placebo. The manufacturer, however, is not willing to give up on what they hope will be a profitable drug.
Dr. Jeremy Kewless from the British Medical Pharmaceutical Society is trying very hard to put a positive spin on these negative results, saying:
“We certainly don’t call migrostat a “placebo”, as we believe there is growing evidence for a mechanism behind the drug.
“However, we still don’t fully understand what is happening pharmacologically, although these reviews suggest that for certain conditions, it is effective.”
Surprisingly, the press is eating up this blatant manipulation. One headline reads:
“Traditional, Non Traditional “Drugs” Both Effective Against Headaches”
So now placebo is a “non traditional drug.”
Are you outraged yet? Imagine the audacity of the pharmaceutical industry – trying to promote a drug that is literally no more than a sugar pill as an effective treatment, in the face of a negative systematic review that shows that it is no more effective than placebo. They actually think they can turn medical science on its head by simply stating that the placebo must also be effective, and calling it a “non traditional drug.” Even more outrageous is the degree to which the mainstream media is simply swallowing this self-serving fiction.
By now you may have seen through my satirical deception. Migrostat is a fiction, but this story isn’t. Simply replace “migrostat” with “acupuncture” and the story is real. Acupuncture works no better than sham acupuncture. It doesn’t matter where you stick the needles – contradicting the entire basis for acupuncture. Jacob Bayous is really Klause Linde, who works at the Center for Complementary Medicine Research at the Technical University of Munich, Germany. Kewless is Dr Mike Cummings, medical director of the British Medical Acupuncture Society.
Of course, when acupuncture is compared to “placebo acupuncture” using opaque sheaths and dull needles that do not penetrate the skin, there is still no difference. Therefore it not only doesn’t matter where you stick the needles, it doesn’t matter if you stick the needles.
The same is true for other pain conditions. A recent review of the literature concluded, for example:
Overall, when compared to sham, acupuncture did not show a benefit in treating knee OA or LBP, but acupuncture was better than a wait-list control and standard of care, respectively.
OA is osteoarthritis and LBP is lower back pain – again, not better than sham (i.e. it doesn’t work) but the emphasis is placed on the unblinded (and therefore less reliable) results. If the proponents of acupuncture were honestly science-based, it would have been discarded years ago. But instead proponents have chosen not to listen honestly to the scientific research. Rather they seek to go through the looking glass where black is white and up is down. If their treatment works no better than placebo – then placebos must also be effective. Further they are shifting to uncontrolled and unblinded studies, because those are the ones that generate positive results. Imagine the pharmaceutical industry lobbying the FDA for unblinded trials because double-blind placebo controlled trials are difficult and often negative.
CAM is all about creatively and deceptively using language to create a double-standard – to defraud the public with ineffective and unscientific treatments.
29 Responses to “Through the CAM Looking Glass”
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Having googled ‘migrostat’ during the first paragraph, I thought Dr. N was losing his grip. Nice twist on presentation.
Yes, you still had me there, Doctor. Although, I was also thinking that “Dr. Jeremy Kewless” was almost too perfect of a name for a guy who appeared to be that clueless. Good job!
I think most people, scientifically literate or otherwise, would be outraged if the pharmaceutical industry behaved as in your story. And yet, the clueless CAM advocates get away with it with hardly a scowl from the media or the public. We must keep working tirelessly to change that situation.
We can go further–how outraged would people be if doctors sold the drugs they prescribe ( and therefore made money by selling drugs)? How outraged would people be if drug companies didn’t state what was actually truly in the bottle (thinking of herbal products that may or may not contain what the label says they do, and also thinking of chinese/ayurvedic herbs that contain actual drugs, heavy metal contaminants, etc). How outraged would people be if the drugs were only tested in vitro and then marketed? It’s clear that CAM plays only by the rules it makes up for itself.
Acupuncture? Funny, I thought it was going to be about homeopathy.
Yes I am outraged! I am just as outraged as the time an ob/gyn of my college of medicine faculty improperly represented acupuncture as a viable treatment. She was clearly awash with the fervor of spiritual & “energy”-based medicine. It’s unfortunate that her past research in alternative birthing methods and C-sections makes her relatively valuable to the program.
How do you deal with someone like this? I wanted to rip her a new one and call her on all her BS, but she is on faculty, and I am just a lowly medical student. I did send an email out to the class with some links to genuine research on acupuncture, but I’m sure very few people took the extra time to read them. For now my plan is to attend every meeting of the CAM interest group and make sure that genuine scientific research gets a fair representation. Anyone with other ideas would be appreciated! I’ve thought about starting a pro-science organization, but I’m not sure the interest would be high. We already have journal club where people present a research paper every week. They do a really great job of teaching students how to properly assess research papers.
You completely had me going for a while. Of course migraine is something that should be quite amenable to the placebo effect because migraine is caused by low NO, by the neurogenic induction of ischemic preconditioning in the brain (sometimes via mast cell degranulation (but there can be other triggers too).
The low NO of ischemia triggers ischemic preconditioning, the high NO following restoration of perfusion causes resolution of the ischemic preconditioning.
The symptoms of migraine are consistent with it being ischemic preconditioning, and very nearly identical with what is called spreading depression. In spreading depression the O2 consumption of brain tissue falls (because ATP consuming pathways are turned off by ischemic preconditioning). There is sufficient O2 present for brain metabolism in spreading depression; it is the regulation of O2 consumption that is off.
OMG! You need to do this as a youtube video. Make the beginning as convincing as possible, cutting to video of actors proving the quotes as soundbites. Then ask your readers and listeners to spread the links around. This one has viral potential!
Geez, guys, just do what I do.
Make Stuff Up and call it the Truth.
it’s so much easier… and profitable.
Daedalus –
If the symptoms of migraines are due to ischemic preconditioning, then what is the mechanism of action for the symptomatic relief seen with caffeine? I know caffeine is a stimulant and vasoconstrictor. Does it act differently in the brain?
medmonkey, It sounds like your ob/gyn faculty member confuses diagnosis using phlebotomy with actual treatment. She could be equating acupuncture with her confidence in other method.
“By now you may have seen through my satirical deception.”
Oh Steve, you’re such a card.
I think the idea that migraine is caused by or associated with vasodilation is mistaken.
http://www.ncbi.nlm.nih.gov/pubmed/18502781
Migraine is reliably triggered by nitroglycerine, however there is no increased perfusion associated with migraine triggered by nitroglycerine.
I go into some detail into the connection between migraine and low NO in my blog on vascular effects of NO. The section on migraines is almost at the end.
http://daedalus2u.blogspot.com/2008/10/role-of-low-basal-no-in-capillary-and.html
I am not sure how caffeine fits into migraine. I have experienced caffeine withdrawal headaches myself, I do not experience migraines. A quick look doesn’t tell me how similar/different they are. Caffeine physiology is pretty complicated. It is an adenosine mimic and adenosine is involved in regulation of energy status and ischemic preconditioning too.
The major treatment for migraine is sumatriptan, which is a serotonin agonist. It also can cause sulfhemoglobinaemia, which is caused by H2S attaching to hemoglobin (and turns blood green). There is cross-talk between NO and H2S. Serotonin is one of the major activators of mast cells, which when activated generate ROS.
I’m guessing you mean reactive oxygen species, daedalus2u, but when I saw ROS, my first thought was “rodents of size.”
[Mental Note: Do not play poker with Dr. Novella...]
Dr N.
I’m not sure if you read the actual articles, but you seem to be missing the point—
http://www.cochrane.org/reviews/en/ab007587.html
“We reviewed 11 trials which investigated whether acupuncture is effective in the prophylaxis of tension-type headache. Two large trials investigating whether adding acupuncture to basic care (which usually involves only treating unbearable pain with pain killers) found that those patients who received acupuncture had fewer headaches. Forty-seven percent of patients receiving acupuncture reported a decrease in the number of headache days by at least 50%, compared to 16% of patients in the control groups.”
That means those who did not receive acupuncture experienced more days of unbearable pain than those who did get acupuncture. Given that, wouldn’t it be sane to ask for the acupunture? (I’m not a big fan of unbearable pain…)
http://www.cochrane.org/reviews/en/ab001218.html
“In the four trials in which acupuncture was compared to a proven prophylactic drug treatment, patients receiving acupuncture tended to report more improvement and fewer side effects. Collectively, the studies suggest that migraine patients benefit from acupuncture, although the correct placement of needles seems to be less relevant than is usually thought by acupuncturists.”
In this case the people getting acupuncture did better than those getting the ‘proven drug’. This is the reason we switch treatment generally, right? I mean when one works better than the other we go with the one that works.
Is there some other point I’m missing?
Yes – these studies were not blinded as to whether or not he subject was getting any acupuncture – only “real” vs “sham”. So as I wrote – the unblinded aspect showed an effect, which is pretty worthless for a subjective outcome like pain. The blinded part was negative.
Also – for those studies that have used the placebo acupuncture, no difference either.
So – we can say it does not matter where or if you stick the needles. That means that any effect was do to other things, like the attention given, conditioning, the ritual aspect of getting acupuncture, the introduction of a novel therapy, etc.
It is the things acupuncture is associated with that is helping – not the acupuncture. Acupuncture does not work.
Just give the patients attention and relaxation.
I’d say lying to effect a “cure” can offer at best a short term benefit. The inference being that there’s a certain neglect involved of potential long term consequences.
But I could be wrong.
Deliberate pretence that a treatment is effective, given to a patient knowingly as a placebo is unethical because of the phenomenon of ‘placebo sag’ where the effect is attenuated over time, and also because evidence exists (do a pubmed search of Ted Kaptchuk or Franklin Miller’s work for example) that deception is actually not even necessary for placebo to be effective as analgesia, or for relief of anxiety-related physical symptoms.
I completely agree with the outrage that would occur if doctors sold their own medications. I recently sent out a group email to seven prominent Australian homeopathic websites asking for some information about how they ensured quality and safety of their preparations, and so far after 3 weeks I have only received one reply. The big companies have not replied at all, and one who did rang my receptionist and complained that she had just taken over the business, and was too busy to respond to my stupid questions. Since it must have taken her several minutes to actually find my office number (which wasn’t on the email) and then several minutes of her time complaining to the receptionist about how hard this internet business stuff is, I still am not sure how she couldn’t have sent me a three-line email about the very rigorous quality control of her products…
[...] will have a very thorough discussion on these reviews. Let’s wait and see… UPDATES Steven Novella discusses the reviews with a very tasteful introduction — Footnotes:* Granted, acupuncture might have a plausible [...]
It is my understanding that migraine is a chronic condition. Treating a chronic condition acutely is not usually the best way. Treating a chronic condition with a placebo such as acupuncture is malpractice.
It is my understanding that every time a migraine attack occurs, there is (or is the potential for) “pruning” of neurons via excitotoxicity. Hyperintense regions are observed in migraineurs and migraine is associated with other cardiovascular disease and with other brain lesions.
http://stroke.ahajournals.org/cgi/content/full/37/4/1109
@daedalus2u – I’ve done caffeine withdrawal once, and it felt very similar to having a migraine. Extremely bad headache, nausea, lethargy, disorientation. But it lacked some indescribable ‘edge’ that migraines have. I wouldn’t reccommend it anyway.
There is so much contradicotory info on migraines out there and it’s terribly frustrating.
My doctor put me on Verapamil as a preventative, and it has decreased the frequency and severity of my migraines. Or at least I think it has. I sometimes wonder if it might just giving me a placebo effect. Is that even possible if I’m suspicious of it?
You can search Verapamil and find that it works reliably for migraines, or it sort of works for migraines, or it doesn’t really work for migraines, or it can’t possibly work for migraines because it’s a vasodilator and that’s what causes them….
And it’s the same for everything else. Foods can trigger migraines, or they can’t. Stress can trigger migraines, or it can’t.
You seem to have some knowledge on the subject, and you’re not coming at it from the angle of a migraineur. How can a lay person sort through the rubbish and find good info? Can you reccommend good sources, or at least warn off of bad ones?
Dr. N- I understand what you are saying about the unblinded and sham acupunture. But-
http://www.cochrane.org/reviews/en/ab001218.html
“In the four trials in which acupuncture was compared to a proven prophylactic drug treatment, patients receiving acupuncture tended to report more improvement and fewer side effects.”
If that statement is true, then the ‘rituals’ of acupunture work better than the ‘proven prophylactic drug treatment.’
So wouldn’t it be wise to do what works? That is the actual question, right? If a ritual is a better pain reliever than a chemical- why not use the ritual? (I’ll bet there is less liver damage from the ritual…)
“I’ll bet there is less liver damage from the ritual…”
Are the proven drugs in these trials known to cause liver damage?
Sonic said >> “So wouldn’t it be wise to do what works?”
Yes Sonic, it would be wise to do what works. That’s why the scientific method exists – to weed out methods that don’t work so we can apply our limited resources to the ones that do work. If it is determined that the sticking of needles in the body is no better than placebo, we must determine what about the “ritual” IS working. For this there is significant evidence that stress relaxation and attention are very important in pain perception and coping. This is why those psychological aspects deserve in depth study, and acupuncture does not.
[...] Yesterday I wrote about a new Cochrane review of acupuncture and migraines. The most significant result of the review was that published studies show no difference between “real” acupuncture and “sham” acupuncture. This is the part of trials that can be blinded – well, single-blinded at least (the subject does not know which is real vs sham, but the acupuncturist does). This blinded data is negative, indicating that it does not matter where you stick the needles, which is a strong indication that the underlying philosophy of acupuncture is false. Further, now that acupuncture studies are being done with placebo acupuncture – opaque sheaths and dull needles that do not penetrate the skin, allowing for double-blind studies – these are also coming out negative. [...]
This was a nicely constructed piece. It’s worth noting, however, that big pharmaceutical companies are not always innocent of the sort of behaviour mentioned in the article. The response to the recent meta-analysis of anti-depressants, which showed that such drugs only have significant benefits for the most depressed patients, is a case in point.
Wilsontown – I completely agree. Pharmaceutical research needs to be kept to the highest standards and transparency, and protocols should be a tight and objective as possible. I simply decry the double-standard for CAM – I want the same high standard for all science-based medicine.
caly, there is no substitute for having an experienced and competent clinician to work with and who uses evidence and science based treatment. I think that is especially true for something like migraine which is common enough for some clinicians to get a lot of experience in it, but with enough individual variation that wide experience is necessary.
Physiology is really complicated and there is more that we do not understood about it than what we do understand. Simply because there are gaps in our knowledge is no excuse to fill them with magic or guesses. There necessarily is a lot of trial and error in finding out what works and what does not work.
I was on verapamil once and had a terrible reaction to it. I had anxiety and depression such as I had not experienced in many years. These effects were obvious after only 2 doses, but I took another dose just to “be sure”. I have PTSD, and this was essentially a continuous flash-back. I understood what was happening so was able to compensate (to some degree). There was no “content” to the anxiety and depression, so I was able to dissociate somewhat from them.
Okay, I didn’t get it like others did until Dr. Novella dropped the ruse. However, who else was thinking “It’s sugar isn’t it? I’m in the placebo group!” while reading it?