January 7, 2010
- In interviews with the press, Edward Scolnick, Merck’s research director, laid out his battle plan to restore the firm to preeminence. Key to his strategy was expanding the company’s reach into the antidepressant market, where Merck had lagged while competitors like Pfizer and GlaxoSmithKline created some of the best-selling drugs in the world. “To remain dominant in the future,” he told Forbes, “we need to dominate the central nervous system.” His plan hinged on the success of an experimental antidepressant codenamed MK-869.
- Behind the scenes, however, MK-869 was starting to unravel. True, many test subjects treated with the medication felt their hopelessness and anxiety lift. But so did nearly the same number who took a placebo, a look-alike pill made of milk sugar or another inert substance given to groups of volunteers in clinical trials to gauge how much more effective the real drug is by comparison.
- In subsequent tests, MK-869 turned out to be no more effective than a placebo. In the jargon of the industry, the trials crossed the futility boundary. (the FUTILITY boundary?)
- From 2001 to 2006, the percentage of new products cut from development after Phase II clinical trials, when drugs are first tested against placebo, rose by 20 percent.
- It’s not only trials of new drugs that are crossing the futility boundary. Some products that have been on the market for decades, like Prozac, are faltering in more recent follow-up tests.
- It’s not that the old meds are getting weaker, drug developers say. It’s as if the placebo effect is somehow getting stronger.
- drugmakers are realizing they need to fully understand the mechanisms behind it so they can design trials that differentiate more clearly between the beneficial effects of their products and the body’s innate ability to heal itself.
- Assumption number one was that if a trial were managed correctly, a medication would perform as well or badly in a Phoenix hospital as in a Bangalore clinic. Potter discovered, however, that geographic location alone could determine whether a drug bested placebo or crossed the futility boundary.
- Convinced that what Lilly was facing was too complex for any one pharmaceutical house to unravel on its own, he came up with a plan to break down the firewalls between researchers across the industry, enabling them to share data in “pre-competitive space.”
- Potter’s ambitious plan for a collaborative approach to the problem eventually ran into its own futility boundary: No one would pay for it. And drug companies don’t share data, they hoard it.
- “The placebo effect was considered little more than a nuisance,” he recalls. “Drug companies, physicians, and clinicians were not interested in understanding its mechanisms. They were concerned only with figuring out whether their drugs worked better.”
- Part of the problem was that response to placebo was considered a psychological trait related to neurosis and gullibility rather than a physiological phenomenon that could be scrutinized in the lab and manipulated for therapeutic benefit.
- US scientists had found that a drug called naloxone blocks the pain-relieving power of placebo treatments. The brain produces its own analgesic compounds called opioids, released under conditions of stress, and naloxone blocks the action of these natural painkillers and their synthetic analogs.
- Placebo-activated opioids, for example, not only relieve pain; they also modulate heart rate and respiration. The neurotransmitter dopamine, when released by placebo treatment, helps improve motor function in Parkinson’s patients. Mechanisms like these can elevate mood, sharpen cognitive ability, alleviate digestive disorders, relieve insomnia, and limit the secretion of stress-related hormones like insulin and cortisol.
- Healthy volunteers feel the benefit of medication plus a placebo boost. Patients who are unable to formulate ideas about the future because of cortical deficits, however, feel only the effect of the drug itself. The experiment suggests that because Alzheimer’s patients don’t get the benefits of anticipating the treatment, they require higher doses of painkillers to experience normal levels of relief.
- Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won’t stop the growth of tumors. It also works in reverse to produce the placebo’s evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.
- “Expectations about pain and pain relief work in a similar way. Placebo treatments tap into this system and orchestrate the responses in your brain and body accordingly.” In other words, one way that placebo aids recovery is by hacking the mind’s ability to predict the future.
- In a study last year, Harvard Medical School researcher Ted Kaptchuk devised a clever strategy for testing his volunteers’ response to varying levels of therapeutic ritual.
- One group was simply put on a waiting list; researchers know that some patients get better just because they sign up for a trial. Another group received placebo treatment from a clinician who declined to engage in small talk. Volunteers in the third group got the same sham treatment from a clinician who asked them questions about symptoms, outlined the causes of IBS, and displayed optimism about their condition.
- Not surprisingly, the health of those in the third group improved most. In fact, just by participating in the trial, volunteers in this high-interaction group got as much relief as did people taking the two leading prescription drugs for IBS. And the benefits of their bogus treatment persisted for weeks afterward, contrary to the belief—widespread in the pharmaceutical industry—that the placebo response is short-lived.
- the geographic variations in trial outcome that Potter uncovered begin to make sense in light of discoveries that the placebo response is highly sensitive to cultural differences. Anthropologist Daniel Moerman found that Germans are high placebo reactors in trials of ulcer drugs but low in trials of drugs for hypertension—an undertreated condition in Germany, where many people pop pills for herzinsuffizienz, or low blood pressure.
- But why would the placebo effect seem to be getting stronger worldwide? Part of the answer may be found in the drug industry’s own success in marketing its products.
- “Before I routinely prescribed antidepressants, I would do more psychotherapy for mildly depressed patients,” says the veteran of hundreds of drug trials. “Today we would say I was trying to engage components of the placebo response—and those patients got better. To really do the best for your patients, you want the best placebo response plus the best drug response.”
(go read the whole article at Wired)
WP
Seems Pharma is far more about licensing than anything else these days.
Comment by speedbird — January 7, 2010 @ 5:53 pm
I think it’s being revealed as having been snake oil all along, bandages over an infected wound. But that’s just my take on it. :)
Comment by Ian — January 7, 2010 @ 6:37 pm
You know I takes drugs for a living right?
I know its all bullshit. Most of these drugs don’t do crap. They are just poisons. But, not really strong poisons. Its hard to generalize, they are all different. But most of them don’t do shit and they keep cranking out new ones to keep making money off of them.
So I am a tester. Lots of people find that alarming and would never do it, but at the same time they buy into Western medicine, which I don’t. I would never take a prescription drug, unless I was getting paid to.
Its like I’ll be a whore but not a sucker.
Comment by Ted — January 7, 2010 @ 6:51 pm
So, this proves that people can heal themselves. The racket of the drug companies is about getting people to give away their power and personal sovereignty. Body sovereignty, community sovereignty. Healing used to be a personal thing and a family thing and a community thing and a cultural thing.
But then it slowly became an impersonal capitalist thing and an impersonal government thing. All these Liberals are wrong too. Free Government Healthcare for everyone won’t give people their power back.
All the power will still be in the hands of “experts” and Government Bureaucrats and The same Pharmaceutical companies.
The way to go is to take responsibility for your own health and well being.
Comment by Ted — January 7, 2010 @ 6:59 pm
I guess no effing cursing allowed, eh?
Comment by Ted — January 7, 2010 @ 6:59 pm
Fucking curse all you want to, though it does end up sounding a bit crass after a while.
And anyway, though I think you’re partially right, there’s a place for health care and doctors and medicine. Somewhere in the article it mentions that placebo’s don’t sure cancer. Sure, doctor’s don’t always cure cancer either, but the help. We’re currently, as a culture, in a place where the body’s ability to heal itself (among other abilities) are discounted in favor of more scientifically controllable processes.
And yes, that’s problematic, but how did we get here? The thing is, science is reliable, incredibly so, whereas simply wishing yourself well is not. What’s needed now is a balancing of the two, a way to open up science to the personal experience, to the powers of subjective thought and belief, without either limiting that power, nor abusing people with it (as science, being impersonal, has a tendency to do).
Its only when we can accept the personal world as it relates to the rational world that we’ll be able to make any progress here…
Comment by Ian — January 7, 2010 @ 7:58 pm
Hey, just figured out what you meant by the “no cursing” comment. Dunno why that comment got spammed, except maybe the mention of drugs. Most of the spam I get is for drugs and porn, so maybe that caused some confusion. But the comment is totally approved by me.
You know, I’d always wondered how you made a living. Good to know. It’s not for me, but I guess its as good as anything if it works for you.
I find your attitude interesting though. Is it that you don’t think the medicine has any major effect? And if you don’t believe in Western Medicine, do you have another system you follow?
Comment by Ian — January 8, 2010 @ 9:35 am
Western medicine is /amazing/ when it’s in the right place. Of course, most of it isn’t.
In fact I think you could say that about most things Western. Guns. Music. You name it.
The issue is this out-of-place-ness. Like, ‘who ordered THAT?’.
*
[My head's full of it, so I have to ask: seen Avatar yet?]
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I am reminded of a (apocryphal?) story of early white settlers pursuing ‘Indians’, way up North towards the Canadian border. The border back then was a line of rocks. The Indians cross the line, the white folk stop at the rocks.
The Indians pull up.
They talk.
‘Who’s your chief?’ asks the Indian
‘King George [?],’ replies Whitey.
The Indian considers.
‘He got some powerful medicine,’ says the Indian, and rides off.
Comment by speedbird — January 8, 2010 @ 4:32 pm
I am into herbs and stuff, exercise, controlling my diet, meditating, working on my breathing and nervous system, balancing my chakras and aura etc. If I broke my arm and needed to get a bone set, I would go to a doctor. But as far as taking drugs for getting too fat and developing high blood pressure, heart problems, diabetes etc. or not dealing with my issues and becoming depressed and wanting happy pills- I am not into that crap.
Comment by Ted — January 8, 2010 @ 4:33 pm
Yes! I loved Avatar! Awesome movie. I don’t care if everyone things its awesome too. It still is! Best movie since Star Ward came out in ’78.
I want to see it again. I loved it on so many levels.
Comment by Ted — January 8, 2010 @ 4:36 pm
Speedbird, King George=George Washington?
So what do Brits know about Indians? Are they popular over there? Have you met any yourself?
I’ve had some interesting experiences with indians.
Comment by Ted — January 8, 2010 @ 4:39 pm
@speedbird:
Yeah, that’s exactly it. I think it comes from the fact that Western Science can’t admit that the personal/subjective even exists. It’s world view doesn’t (maybe can’t) involve the first person perspective, so that’s where all it’s faults end up lying.
And, no, I haven’t seen Avatar yet. I do want to, but I do not have high expectations, other than the awesomeness of the effects.
That story brings to mind something from Gurdjieff’s “Meetings With Remarkable Men” where a young Yazidi child is trapped in a circle by some other kids and we learn that the Yazidi people are incapable of breaking out of any complete circle they are placed within. It’s later revealed that Yazidi are “devil worshippers”, though what one had to do with the other was never really clear to me…
@Ted:
Yeah, me either. I’ve refused anti-depressants several times, and am happy to say that I definitely no longer need them.
Comment by Ian — January 8, 2010 @ 4:51 pm
>> I loved Avatar!
Yeah, me too. Possibly the best sci-fi since… well, since ‘Aliens’… ;D
>> King George=George Washington?
Dunno. Maybe King George of England, way back in the day.
‘Indian’ over here means curry. But we studied the settlement of America at school. All sorts of really gnarly stuff like ‘How is the native American’s definition of “medicine” different from the European definition? Discuss.’ And when I’ve had the chance to visit the States and Canada I’ve tried to keep an eye open.
Comment by speedbird — January 8, 2010 @ 5:02 pm
>> I do not have high expectations
I didn’t either, but I was very pleasantly surprised.
>> Western Science can’t admit that the personal/subjective even exists
I guess that’s it. That’s the price the Enlightenment paid for releasing the genie from the bottle.
Comment by speedbird — January 8, 2010 @ 5:07 pm
Well, it can hard to get to know them. I mean, not in the sense of meeting a native person on the street and having a conversation (of course that can be hard too) but in the sense of developing relationships and connecting spiritually.
I wanted to connect with some Indians since I was a little kid and found it to be really hard and also, on one hand its not good to stereotype, even in a positive way, thinking they will all be really spiritually inclined and connected to the Earth, but on the other hand, I find some really are like that. Of course In the UK and Europe there are people living on ancestral lands for generations and generations also.
Comment by Ted — January 8, 2010 @ 7:05 pm