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.

Pebbles I stumbled on this week (notables from the web)

A Chopin Nocturne...

from Derek Bownds' MindBlog by [email protected] (Deric)

Bownds blogs on neuro matters -- and, each week, posts a video of him playing a bit of classical music on his piano. Gotta like it.

FDA To Mine Big Databases For Safety Problems

from Pharmalot

The effort, called Sentinel Initiative,
will be the first time the FDA will have an opportunity to monitor
almost immediately how drugs are affecting the public. To do so, the
agency will mine databases of more than 20 million patients who receive
their drugs through Medicare. The idea, of course, is to catch side
effects that might otherwise go undetected for months or years.

Also covered at the Wall Street Journal Health Blog

A Musical Aptitude Section Of The Genome?

from Scientific Blogging - Neuroscience

Molecular and statistical genetic studies in 15 Finnish families have shown that there is a substantial genetic component in musical aptitude.

Musical aptitude was determined using three tests: a test for auditory structuring ability (Karma Music test), and the Seashore pitch and time discrimination subtests. The study represents the first systematic molecular genetic study that aims in the identification of candidate genes associated with musical aptitude.

File this under "Interesting if true" -- or what scientists call "needs replication."

As General Surgery Ranks Dwindle, Patients May Suffer

from WSJ.com: Health Blog by Sarah Rubenstein

Sexual Dysfunction On Anti-Depressants Higher Than Thought, Longer Lasting

from Furious Seasons by Philip Dawdy

Thanks to CL Psych who flagged this issue the other day and posted one academic paper acknowledging that not only are there weird problems such as genital anesthesia--such a polite term--connected with anti-depressant use in some cases, but that the rate of sexual dysfunction on the happy pills isn't very happy at all. In fact, it's much higher than doctors have commonly assumed and than pharma companies have been willing to admit.

Dawdy -- a fearless chronicler of others' and his own experience with depression and antidepressants -- notes that he himself experienced no sexual side-effects.

The shifting sands of the 'autism epidemic'

from Mind Hacks by vaughan

The Economist has a short but telling article on whether the so-called 'autism epidemic', occasionally touted in the media, may simply be a change in how developmental problems are diagnosed.

It covers a new study that did something really simple - it tracked down 38 people who, years ago, had been diagnosed with a delay in language and re-assessed them using the latest diagnostic interviews.

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

Slate asks: Are MDs shilling for pharma ... on public radio?

In a nifty bit of reporting, veteran health reporters Shannon Brownlee and Jeanne Lenzer revealed in "Stealth Marketers," a story on Slate, that a "Prozac Nation: Revisited," a radio piece on antidepressants and suicide that ran on many public radio stations recently, "featured four prestigious medical experts discussing the controversial link between antidepressants and suicide" who all reportedly have financial ties to the makers of antidepressants -- as does the radio series, known as "The Infinite Mind," that produced the show.

As the story notes, the extent of the financial ties are unknown because those involved won't reveal them. Still, Brownlee and Lenzer argue, the show in question, "Prozac Nation: Revisited," "may stand in a class by itself for concealing bias." (Then follows a troubling paragraph outlining the conflicts of interest involved.)

is that undisclosed financial conflicts of interest among media sources seem to be popping up all over the place these days. Some experts who appear independent are, in fact, serving as stealth marketers for the drug and biotech industries, and reporters either don't know about their sources' conflicts of interests, or they fail to disclose them to the public.

The story goes on to list several examples that point out out badly such influence compromises our ability to trust many news reports.

Conflicts of interest abound even in unexpected places. A recent survey of academic medical centers published in the Journal of the American Medical Association found that 60 percent of academic department chairs have personal ties to industry—serving as consultants, board members, or paid speakers, while two-thirds of the academic departments had institutional ties to industry. Such ties can be extremely lucrative. And according to these articles in the medical literature, researchers who receive funding from drug and medical-device manufacturers are up to 3.5 times as likely to conclude their study drug or medical device works than are researchers without such funding.

Brownlee and Lenzer put some focus on journalists as well. They cite one study of 544 science stories from top outlets (from 4/06 to 4/08) that checked whether the journalists quoted an independent expert and/or made some attempt to report researchers' potential conflicts of interest. "Half the stories failed to meet this requirement."

This doesn't surprise me. This story prompted a very lively exchange on a science writer listserve I participate in. That exchange confirmed that there's wide variation in how consistently researchers (and the institutions they work for) reveal their funding sources and in how often or consistently journalists ASK their sources about their funding resources. Science journalism is a field ever in tension between an excitement over the scientific discoveries in question and the more hard-nosed mission to vet the reported results and examine science as a social, political, and commercial activity. Most science journalists are ever balancing interest and enthusiasm with skepticism and critical thinking. They should do so conscientiously, of course; that's their job.

As Brownlee and Lenzer note, it's impossible to know at this point a) how much money some of the people involved actually got from drug companies and b) of course, how much it influenced them. But it's well-establshed that trust in scientific results -- especially in the much-tainted arena of psychiatric drugs -- depends on a transparency in funding that has been sorely lacking. This sort of thing -- undisclosed funding from pharm interest of a show that purports to EXAMINE the controversy over antidepressants and suicide -- can't help matters.

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

Psychiatry Handbook Linked to Drug Industry

From Well, Tara Parker-Hope's health blog at the NY Times:

More than half of the task force members who will oversee the next edition of the American Psychiatric Association’s most important diagnostic handbook have ties to the drug industry, reports a consumer watchdog group.

The Web site for Integrity in Science, a project of the Center for Science in the Public Interest, highlights the link between the drug industry and the all-important psychiatric manual, called the Diagnostic and Statistical Manual of Mental Disorders. The handbook is the most-used guide for diagnosing mental disorders in the United States. The guide has gone through several revisions since it was first published, and the next version will be the D.S.M.-V, to be published in 2012.

The American Psychiatric Association’s Web site has posted the financial disclosure of most of the the 28 task force members who will oversee the revision of the D.S.M.

It’s not the first time the D.S.M. has been linked to the drug industry. Tufts University researchers in 2006 reported that 95 — or 56 percent — of 170 experts who worked on the 1994 edition of the manual had at least one monetary relationship with a drug maker in the years from 1989 to 2004. The percentage was higher — 100 percent in some cases — for experts who worked on sections of the manual devoted to severe mental illnesses, like schizophrenia, the study found.

Steroids for the Brain? Nature Survey Finds Many Neuro-Pill-Popping Scientists

We've seen our brain on drugs. Here's the dope on brainy people on drugs.

Survey results of 1400 scientists (or Nature readers, anyway) on use of neuroenhancers
Figure from Nature, "Poll results: look who's doping"

With baseball's steroid scandals seemingly behind us now -- or at least considered less newsworthy -- the press has recently turned some of its steroidal attention to neuroenhancement among major league academics. The journal Nature has taken the lead here, publishing a commentary in early March by two Cambridge University researchers who "reported," as a nicely turned New York Times story by Benedict Carey noted, "that about a dozen of their colleagues had admitted to regular use of prescription drugs like Adderall, a stimulant, and Provigil, which promotes wakefulness, to improve their academic performance. The former is approved to treat attention deficit disorder, the latter narcolepsy, and both are considered more effective, and more widely available, than the drugs circulating in dorms a generation ago."

Carey's article (and others, too; see below) is well worth reading.* But the news today is that Nature ran an open, online survey at its web site and found that 20 percent of those responding said they had used neuroenhancers such as Ritalin (an amphetamine used clinically for ADHD) and modafinil (a "wakefulness promoting" narcolepsy drug that has seen wide off-lable use not only for ADHD and depression but for increasing concentration, working memory, and other cognitive assets).

An online survey is hardly scientific, as it's likely to attract respondents with a, um, demonstrated interest in the subject. And this one was likely further warped by press attention that brought outside (i.e., possibly non-scientists) to take it.

That said, the 20 percent figure won't surprise anyone who hangs out at scientific conferences, where use of modafinil is talked of fairly casually. Many of those who use modafinil consider it a healthy substitute for coffee: better effects, fewer side effects, no demonstrated long-term harm. It sharpens attention, adds stamina, increases the power to resist distraction, and creates a smoother energy curve that lacks the jittery buzz that lots of coffee will predictably create. And some find it interferes less with sleep.

So is this bad? That question seems to flummox everyone. On its face, seemingly so: It's a drug, and we don't take drugs just to boost performance. This sits fine until you think about coffee. Is modafinil is simply a better coffee?These questions make it clear we're on a slippery slope. We'll be seeing a lot more handwringing and headscratching on this one.

Some of the more intriguing coverage so far:

The original Nature commentary, "Professor's little helper." (Nature subscription required)

An interesting pro-con discussion among academics at the Chronicle of Higher Education website.

An advice column at Wired about the competitive threat that neuroenhancement poses in the office environment. The answer, unfortunately, completely the cognitive enhancement of the drug in question (modafinil), advising the non-drug-doer to better his modafinilly enhanced coworker-competitor by working smarter rather than longer.

An fake April Fools Day press release from (not really) the NIH announcing "three new initiatives to fight the use of brain enhancing drugs by scientists." This fooled a lot of bloggers.

* The Carey article visits the inevitable comparisons with steroids in baseball. Some quoted in the article argue that academics taking drugs is different than athletes taking drugs because competition in academics in secondary -- an assertion that may strike many as questionable, given the intense competition not only for tenure but for glory and riches once tenure is secured. The most prominent scientists do well indeed. Those that don't make the cut, not so. As one anonymous scientist said of his thrice-daily does of Adderall in the the Times article, "“I’m not talking about being able to work longer hours without sleep (although that helps). I’m talking about being able to take on twice the responsibility, work twice as fast, write more effectively, manage better, be more attentive, devise better and more creative strategies.”

He makes a good point that is often missed: These drugs don't just pep you up; they sharpen and focus the brain, creating a double enhancement.

Roundup of notables: The Certainty Epidemic, Dog Head Poetry, et alia

Some great stuff I've come across, lack time to blog on, but would hate for you to miss:

In On being certain, neurologist and novelist Robert Burton, who writes a column at Slate Salon, looks at the science of what makes us feel certain about things -- even when we're dead wrong about them. His book on the subject, which I read in advance copy a while back, is fascinating fun reading. The most startling (and disorienting) finding he describes is that, from a neurocognitive point of view, our feeling of certainty about things we're wrong about is pretty much indistinguishable from our certainty about things we're right about. Not something to think about when you're in the middle of an argument -- or maybe it is, because maybe it's the other guy who's certain but wrong. Hard to know!

Why are drug costs are going up?"Because they can," say the folks at Managed Care Matters

From Cognitive Daily, When we see a brain "light up," [most of] our brains shut off. How we are suckers for brain-scan pictures.

Mind Hacks drew attention to the wonderful poem below by Wislawa Szymborska, which is a reaction to a not-so-wonderful film, from 40s Soviet science, of a decapitated dog head that (supplied with blood) still reacts to many stimuli. Grim film, beautiful poem. Excellent commentary and links at Mind Hacks.

The Experiment
by Wisława Szymborska

As a short subject before the main feature -
in which the actors did their best
to make me cry and even laugh -
we were shown an interesting experiment
involving a head.

The head
a minute earlier was still attached to...
but now it was cut off.
Everyone could see that it didn't have a body.
The tubes dangling from the neck hooked it up to a machine
that kept its blood circulating.
The head
was doing just fine.

Without showing pain or even surprise,
it followed a moving flashlight with its eyes.
It pricked up its ears at the sound of a bell.
Its moist nose could tell
the smell of bacon from odorless oblivion,
and licking its chops with evident relish
it salivated its salute to physiology.

A dog's faithful head,
a dog's friendly head
squinted its eyes when stroked,
convinced that it was still part of a whole
that crooks its back if patted
and wags its tail.

I thought about happiness and was frightened.
For if that's all life is about,
the head
was happy.

We all seem convinced we're right about politics, religion or science these days. What makes us so sure of ourselves?

News

Feb. 29, 2008 | Certainty is everywhere. Fundamentalism is in full bloom. Legions of authorities cloaked in total conviction tell us why we should invade country X, ban "The Adventures of Huckleberry Finn" in schools, eat stewed tomatoes, how much brain damage is necessary to justify a plea of diminished capacity, the precise moment when a sperm and an egg must be treated as a human being, and why the stock market will revert to historical returns. A public change of mind is national news.

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.

Placebo effect stronger if you pay more

With so much written here lately about placebos and drug effectiveness, I would not want to leave out this remarkable study: Placebo effect is stronger, apparently, if you pay more for the placebo.

This is a fascinating study described in a letter to the Journal of the American Medical Association. A crudely shortened version: Some researchers at MIT (none of them Bill Murray, as far as I can tell) gave light shocks to volunteers, then gave them some placebos that were costly and some that were cheap. The costly ones worked better.

It sounds like a bit of a stunt, but as Respectful Insolence points out in a nice write-up, the finding is perfectly consistent with what we know about placebos. It would seem to have unsettling implications for lowering health-care costs.

An excerpt is below the break; study is here, but behind a pay firewall.