Smooth Pebbles

How big is the placebo effect in depression?

The evidentiary landscape regarding antidepressant efficacy seems to grow ever more slippery. Now comes a study, drawn to my attention by the busy-eyed Philip Dawdy at Furious Seasons, that finds that the beneficial effects of placebo treatment of depression last longer than generally thought.

As the study's authors note, "The assumption that the placebo response in depression does not endure is widely held and often stated in writing." In particular, many seem to assume that placebo effects fade while effects of actual medications persist -- another argument for antidepressants.

The point here is not that antidepressants never work. It's that the strength and breadth of the placebo is so strong -- placebo helped 80% as many patients in this study as did real antidepressants -- that it greatly complicates evaluating real antidepressants at either the individual or population level.

I've not had time to closely the study in question, which was authored by a team dran from Duke, Brown, and Tufts. As the authors note, their meta-analysis drew on a fairly large patient base -- 3063 patients -- but included only 8 studies, apparently because they could only find that many that ran the trials long enough to test the question whether placebos worked long-term. (In this case, long-term means 12 weeks. Most antidepressant trials run pretty short, which is another of their many significant limitations.) Even with those caveats in mind, however, this seems a pretty startling and significant finding.

Furious Seasons's take:

Via Furious Seasons

Placebo Effect In Depression Treatment Much Larger Than Previously Thought

CL Psych made me aware of an explosive study in the August Journal of Psychiatric Research which contends that the placebo effect in anti-depressants is much larger than I think anyone in the research world expected. It's a meta study re-analyzing eight anti-depressant trials comprising 3,063 people diagnosed with depression. The study was done by Arif Kahn et al. Kahn is well known in the research world and runs a large clinical research facility in the Seattle area. So he's a long way from being an anti-meds advocate.

In the study, which looked at trials that went longer than 12 weeks (some went as long as 12 months), Kahn found that 79 percent of patients on placebo remained well compared to 93 percent of anti-depressant responders. That would give an overall effect size of the anti-depressants studied of 14 percent, well under the usual 25 percent to 30 percent in shorter anti-depressant trials. I cannot tell from the abstract what specific anti-depressants were involved, but for a sugar pill to perform nearly as well over time is astonishing. Eye-opening even.

Dawdy at Furious Seasons further notes:

In his study, Kahn offered this assessment:

"The widely held – and probably erroneous – belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking."

That was the study's final sentence. It'll be interesting to see if this gets replicated.

GIN, TELEVISION, and COGNITIVE SURPLUS

Hi Readers.

Wanted to clue you in to a couple web pleasures. One is Edge: GIN, TELEVISION, AND COGNITIVE SURPLUS A Talk By Clay Shirky, in which Shirky talks about how society's "cognitive surplus" -- the time and brain power contained in the free time created by the Industrial Revolution and the 40-hour work week -- has moved from building cultural infrastructure (libraries, democracies, museums) in the 19th century to TV in the post-War 20th century and the Internet (at least for many people) in the 21st century.

The benefit of this last move, Shirky argues, is that the Internet can actually put some of this cognitive surplus to work, as it does on, say Wikipedia. (This all came to Shirky's mind, he explains, when a TV producer he knew said of people writing and editing Wikipedia ,"Where do they find the time?" and Shirky thought, "They take it from your TV programs!")

It's a good riff with some interesting implications -- though, as someone who didn't even have time to watch Shirky's whole 16 minute video lecture (I read the transcript instead), I can't quite relate to the free time thing. But then, I don't get TV, and I'm a freelancer, so no 40-hour work week, and these kids ... Oy. Time?

But apparently some people have it, and while some watch TV, Shirky has interesting things about the ones who are using the Internet to apply their cognitive powers by producing rather than just consuming.

Tags: ClayShirky, Very Short List, internet, industrial revolution, leisure time, cognitive surplus

More questions on cell phone/DNA data

You want mail, write about cell phones and DNA.

Earlier today, when I posted a heads-up to a Science story about questions raised about data-tampering in what Science called "The only two peer-reviewed scientific papers" showing strong links between cell phone use and DNA mutations, I noted I was surprised at the lack of press coverage about this, given how heavily most papers on the subject are reported. Two hours later I got a note from Louis Slesin, who blogs on such issues at Microwave News, asserting that the Science story oversimplified the situation. Slesin pointed me to his Sept 3 blog post:

Making sweeping statements about scientific knowledge is always challenging, especially when writing about an unfamiliar field of research. Take, for example, this opening sentence from an article, "Fraud Charges Cast Doubt on Claims of DNA Damage from Cell Phone Fields" by Gretchen Vogel in this week's Science magazine:

"The only two peer-reviewed scientific papers showing that electromagnetic fields (EMFs) from cell phones can cause DNA breakage are at the center of a misconduct controversy at the Medical University of Vienna."

Sweeping ... and wrong. Not counting the two papers from Hugo Rüdiger's lab in Vienna, here are 11 papers that point to changes in DNA breaks following exposures to cell phone radiation:

Slesin then lists those papers as well as some others before concluding:

None of this should be interpreted as indicating that the cell phone–DNA issue is closed. Others have failed to see such genetic effects and the jury is still out. But clearly to state that only two papers have shown DNA breaks is grossly misleading —no, simply wrong. We have been closely following the University of Vienna story for some months and we will be reporting on it in detail sometime soon. The Science story gives but a glimpse of some of the maneuvering going on behind the scenes; in this case, manipulating the media to influence public opinion. At the moment, we are still trying to sort out who is doing what.

Did Science cut to the chase or oversimplify? As I'm trying to finish another story right now, I lack the time to run all this down. But this latest wrinkle in the Do cell phones harm you? debate strengthens my impression that a tangle of passionate interests (profits, reputations, righteousness, and a world of ambivalent feelings about connectedness, technology, and the risks posed by the human-made environment) are at work here, greatly complicating the supposedly-but-rarely-straightforwardly-objective path of science and its understanding.

I'll try to keep up with this and report further. Feel free to keep me posted or chime in via the comments section.

Tags: cellphones, fraud, Science magazine, Louis Slesin, Gretchen Vogel, Medical University of Vienna, cell-phone study, DNA mutations, Hugo Rüdiger, scientific misconduct

Measles is back, and it's because your kids aren't vaccinated: Scientific American Blog

This one's causing a dust-up over at the Scientific American's "60-Second Science" blog

Measles is back, and it's because your kids aren't vaccinated
David Biello

If you didn't vaccinate your kids, you too could find yourself partly responsible for the resurgence of a disease thought eliminated in 2000.

Measles—a highly contagious disease-causing virus—is making a comeback in the U.S., thanks to parents fears over vaccines. Fifteen children under 20, including four babies, have been hospitalized and 131 sickened by the red splotches since the beginning of this year in 15 states and the District of Columbia, according to the U.S. Centers for Disease Control.

The CDC had announced in 2000 that the disease was eliminated in the U.S. thanks to a vaccine that can completely control it. But fears of autism have led some parents to forego this treatment and at least 63 of the sickened children were unvaccinated.

Peditrician Pauline Filipek of the University of California, Irvine told ScientificAmerican.com this spring that parents who don't vaccinate their kids are putting the tykes at risk of long-forgotten diseases, like measles. What they're not doing: preventing autism.

"Many, if not most, of the younger siblings [of autistic children] never have any vaccinations," says Filipek, who believes that autism is not caused by vaccines. "And they are as autistic as the day is long."

Catch more at:

Measles is back, and it's because your kids aren't vaccinated: Scientific American Blog

Tags: measles, vaccines, autism, health, epidemiology, Scientific American

A Fine Flap Over Pharma Influence on Medical Reporting

A couple weeks ago Slate ran a piece asking "Are doctors shilling for drug companies on public radio?", which I took brief note of in a previous post.

Now I've written up a longer reaction (actually a reaction to the reaction to the Slate story) for Columbia Journalism Review's "Observatory" blog, which covers science journalism. The gist:

If journalists ... want the information they present to the public to be taken as credible, they need to err on the side of transparency, presenting not only the voices but also the relevant financial interests of the experts they feature. Failing to do so only damages message and messenger alike. But in the wake of the repeated scandals about drug-company concealment of drug-trial data, it’s strange that I have to spell this out.

As expected, this generated some blowback from people less worried than I about the trust problems created by failure to disclose potential conflicts of interest in experts quoted in medical stories. I expected, for instance, to be accused of trying to end all links between doctors and drug and device developers or to shush doctors with such ties from public discussion, and I was, at least indirectly. Yet as I noted in the comments column:

I am not proposing that doctors or researchers with financial ties to industry be excluded from press stories or public discussion of medicine. That would be destructive. I am arguing that the relevant financial ties of quoted experts should be disclosed so that the public can consider those in considering their positions. Butterworth appears averse to this idea. But it's one that the leading medical journals have embraced, and it seems to have raised rather than eroded faith in the studies published in those journals.

The issue of industry influence on medical opinion is a rich one; may this little squabble shine a bit of light on it. Check it out at "To Disclose or Not to Disclose."

Technorati Tags: Brownlee, Jeanne Lenzer, journalism, Lilly, pharma, Slate

Did Antidepressants Depress Japan?

The Kirsch study published a few weeks ago has stirred much discussion of the placebo power of antidepressants (or is it the antidepressant power of placebos?); it's clear that the act of taking a pill that you expect to help you often does help you.

But can the availability of a pill meant for depression make you feel (or think of yourself as) depressed? That's the question behind another part of the drug debate, regarding whether the drug industry encourages us to medicalize ordinary experience.

In pondering these things I ran across this fascinating New York Times >article from 2004, "Did Antidepressants Depress Japan," about the introduction of the concept of depression in Japan beginning in the late 1990s. Before then, the article asserts, Japanese culture concerned itself little with depression outside of professional psychiatry and medicine. But when drug companies started pushing antidepressants beginning in 1999, a cultural awareness of depression grew -- and with it, the number of people who considered themselves depressed.

All arguments about the reality of severe depression aside, this says remarkable things about how cultures define -- and individuals experience (or not) -- a state of ill-being. The story is excerpted below the break, or read the whole thing here.

Drugs in Your Drinking Water

This one's getting a lot of play: There are traceable levels of prescription drugs in many public water supplies.

The Times includes the AP story, which is both long and good. I bumped into it first on the Wall Street Journal Health Blog:

Health Blog : Big Pharma is in the Water Big Pharma is in the Water Posted by Sarah Rubenstein

It's not so expensive to get pharmaceuticals after all: Just drink water.

An investigation by the Associated Press found trace amounts of scads of drugs in drinking-water supplies around the country. For a list of what was found in the watersheds of 28 metro areas, click here. Among the water's offerings were antibiotics, anti-convulsants, mood stabilizers and sex hormones. There were traces of sedatives in water serving the city that never sleeps.

The drugs get in the water via our own waste.

Clive Thompson looked at the ability to trace drugs in water supplies -- a "community urinalysis," as he called it -- in a brief item in the NY Times Magazine's "Ideas" issue.

Do these drugs have any effects? The drug content is pretty low, but as one scientist points out in the Times story, these drugs are meant to have effects at low doses. As the Times story notes in signing off:

''We know we are being exposed to other people's drugs through our drinking water, and that can't be good,'' says Dr. David Carpenter, who directs the Institute for Health and the Environment of the State University of New York at Albany.

From Wall St Journal: "Employers Pick Workers’ Pockets on Health Insurance"

Why aren't your wages going up? Maybe because you're the one paying for the health insurance your boss is supposedly paying for.

That's the gist of a new commentary in JAMA, which I'd missed till the Health Blog at the Wall Street Journal brought it to my attention: "Who Really Pays for Health Care?," the recent commentary by bioethicist Ezekiel Emanuel and economist Victor Fuchs,  argues that employer-provided health care is not as valuable a benefit as it is cracked up to be because employers basically pull it from pay raises employees would get otherwise. The result, the article says, is that you get flat or declining real wages, which is exactly what many workers have received the last decade or two. Thus along with management taking an increasing share of company income, rising health premiums are a main reason wages have been flat.

"Why does this myth matter?" ask the WSJ Health Blog --

Emanuel says that people’s belief that they’re getting a free benefit is a big reason why they are resistant to a major overhaul of the health care system. But employer-based health care is economically inefficient, Emanuel tells the Health Blog. A substantial chunk of the money goes to pay for things that have nothing to do with health care, such as underwriting, sales and marketing.

Uwe Reinhardt, a Princeton health economist, likens the employer-based health insurance to a garden party where a very slick pickpocket steals your wallet and then buys you roses and chocolates. “You’d be very grateful,” Reinhardt tells the Health Blog. Employers “are pickpockets who very skillfully take it out of your paycheck. Then they say, ‘Now genuflect.’ ”

The JAMA article is here, behind a paywall; the WSJ blog piece is here.

Tags: heath_insurance, health_care

"No more scavenger hunts," says Nature of SSRI-placebo study

A quick heads-up: Nature weighs in on the flap over the Kirsch SSRI study that found antidepressants no more effective than placebo. I've given a lot of attention to the placebo issue. Nature stresses another point: That the Kirsch study underscores the need for clinical trial data to be public. At present it is not, as the drug companies have persuaded the FDA that releasing all trial data might reveal trade secrets. Nature argues -- as have many -- that what's being hidden is not proprietary trade secrets but information vital to public health:

No more scavenger hunts

The recent media flap over antidepressants highlights the need for data to be transparent %u2014 and for a mandatory database of all clinical trials.

It was not the media's finest hour. When a study was released last week challenging the effectiveness of several popular antidepressant drugs, some news outlets, particularly in the United Kingdom, responded with headlines blaring 'the drugs don't work' %u2014 even though the drugs often do work. Yes, the study showed that the drugs often performed no better than a placebo. But what many of the media missed was that the placebo effect can be remarkably strong in psychological and neurological disorders, especially in mild depression. Doctors scrambled to assure patients that they should not abandon treatment.

Almost buried in the hubbub, though, was a more important story. To access the data needed for this study %u2014 a meta-analysis of 35 clinical trials %u2014 the researchers had to file a Freedom of Information Act request with the US Food and Drug Administration. And the information they finally received was incomplete: crucial data were missing for several studies that failed to find a significant benefit of the drug compared with the placebo. The missing data limited the analysis, and forced the researchers to abandon their investigation of two drugs altogether.

Such data chaos has become all too familiar in the world of clinical trials. And that fact, combined with recent scandals about antidepressants, diabetes drugs and cholesterol medications, has spurred an outcry to make clinical-trial registries mandatory.

More at the Nature website.

Slippery Ground: SSRI-Study Fallout Spreads

photo © iStockPhoto/AnikaSalsera

The ripples from the PLOS Medicine antidepressants-don't-work study by Kirsch et alia, which I covered below, just keep spreading. Those who want to follow it can do well by visiting or bookmarking this search I did (an ingenious Google News search for "Kirsch SSRI"). It seems to be tracking the press coverage pretty well. Note that the heavier and higher-profile coverage comes mainly from UK. As far as I can tell, none of the top 3 or 4 US papers have yet covered it.

This blog search should help as well.

Some of the more notable responses since yesterday:

Science weighs in. The Times Online (UK), with a hat top to SSRI as antidepressant, opines that "If it's all in the mind, fine."

The searches above will find more.

As many have noted, that antidepressants barely best placebo is not big big news; other studies have found that the drugs barely best placebo. But the starkness of Kirsch's "no effect" finding -- and the paper's assertion that there seems no reason to prescribe except for the deeply, dangerously depressed -- seems to have sparked a deeper examination of this issue than previous studies have. The anguish you see in many posts and comments, especially by doctors and depression sufferers, is that of an entire discipline and patient base having to confront the profound ambivalence of the data and the plain wierdness of the way in which psychiatric drugs work. Many drugs depend heavily on a placebo effect, of course. But the mind-body mystery raised by placebo effects in antidepressants presses itself more insistently, since "the body" doesn't seem so much in play.

This is slippery territory; not surprising that many are having trouble finding their footing.