Psichiatria

Pharmageddon

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Q&A: Psychiatrist Dr. David Healy Defines ‘Pharmageddon’

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PHIL ASHLEY / GETTY IMAGES

Dr. David Healy has spent decades delving into the dark corners of the pharmaceutical industry, where, for instance, drug companies have tried to hide the worrisome connection between antidepressant drugs and suicide. In the psychiatrist’s best-known previous books, The Antidepressant Era and Let Them Eat Prozac, Healy explored the often vexing history of the mental health field and its troubled relationship with Big Pharma. In his latest book, Pharmageddon,he presents an even bleaker picture of the way industry has co-opted medicine in general — not just mental health. Healthland spoke with Healy about his findings.

What do you mean by ‘pharmageddon’?

At the moment, treatment-induced death is the fourth leading cause of death [overall], and within the mental health field, it’s probably the leading cause of death.

It’s a little bit like climate change. It may feel great to have a car, the convenience you get is a thing we appreciate each time we hop in the car and drive down to the market. But the use of cars is contributing to the bigger picture of climate change. In the same way, quite a few medications we take produce good outcomes. But we’ve [had a] climate change in medicine, which runs the risk of completely destroying medicine as we’ve known it.

And the key tool in all of this is how companies use the scientific evidence. They construct trials to get the outcomes they want; they only publish positive trials. The study often shows the opposite of what the data actually shows.

In the book, you look at how drug companies sell us on reducing risks — like say, high cholesterol — that may not actually do much to keep us healthy because high cholesterol itself is just a marker for cardiovascular disease risk, not an illness itself.

If you [look at] statins to lower cholesterol or drugs for osteoporosis, there’s no obvious benefit like there is from wearing a parachute when you jump out of a plane. You often just don’t feel good and you may feel a good deal worse. There isn’t even a proven benefit at the end. What you’ve got is proof in the sense of demonstrating that over a six-week period, you can show a marginal change that we have agreed to call a change for the ‘better.’ [The point is that the measure doesn’t necessarily mean your health will improve, but rather is just a marker linked with a reduction in risk.]

Trials get used as tool to persuade doctors to persuade you to have treatment. [And making drugs] available on prescription only is a means to persuade you to take things that if you were more naturally cautious, you’d be less inclined to take.

But don’t we need clinical trials to eliminate quack remedies and look systematically at the best treatments?

There’s two [situations] where trials are useful. There’s an area were you don’t need trials at all, where the treatment really works, such as antibiotics for serious infections. And they’re also really useful when they show that something doesn’t work.

What we’ve got is what’s in between, where in actual fact [some] people would say, for example, if you take all the trials of antidepressants, they actually show that the drugs didn’t work.

MORE: New Research on the Antidepressant-vs.-Placebo Debate

Yet many people say they experience profound changes after taking the antidepressant drugs like Prozac — some positive and some negative.

That’s not saying that they don’t work — a bunch of people swear that they’re working. The problem is that if we had all the data available [including the data that the drug companies hid], we ought to have said, ‘We’re not impressed by these drugs. We need to go to back to the drawing board and find the people who really benefit.’ There’s a bunch of people on [antidepressants] who clearly do well. But the companies have made whatever billions of dollars [selling them to a lot of people who don’t].

What do you think about the link between antidepressants and suicide? You’ve found some pretty damning evidence that healthy people may become suicidal or aggressive when they take these drugs.

There’s a group of people for whom antidepressants in general work awfully well, but there’s also a group for whom they don’t work well and they can become either violent or suicidal. The problem again comes back to the role of the doctor. If doctors can’t see that drugs may be good and may be bad, that they can be useful and problematic — if they aren’t experts and can’t handle a bit of complexity — they’re going to go out of business. The problem with doctors and antidepressants making people commit suicide is when it first came out about some children being suicidal, the American Psychiatric Association said that it believed that antidepressants save lives.

I’ve been trying to say to doctors, this is a professional suicide note. What they should say is, Psychiatry can save lives. We know that these pills are good for some and not others and it takes expertise to manage this. If don’t take that [perspective], well, there are cheaper people like nurses, and if pills have no risk and work well, there are cheaper people going to be prescribing.

Why do you emphasize the issue of prescribing privileges so much?

When you come to me for treatment, in sense you’re my hostage. If I ask you if something is wrong [in terms of side effects, you say], ‘No, things are fine.’ You may be having strange thoughts, you may be getting aches and pains you didn’t have before, but the problem is that you either want to keep me happy and so you don’t mention it, [or you say nothing] because I’ve told you that you have to be on these pills because otherwise you will have a heart attack or stroke. You may not even know that the problem is caused by the pill. As a doctor, I’m not trained to pick up that these things may be going on.

The other I’m thing not trained in is that when things are available by prescription only, it’s me, the doctor that ‘consumes’ the pill. I’m the consumer in the sense that companies market these drugs [to me] — in the case of pharma, they’re spending more on marketing than Apple spends or Microsoft or GM. [While those companies] market to all of us, the amount of dollars per head is small. But pharma markets to doctors. Direct-to-consumer ads are only a small part of budget and they’re designed not [just] to get you to believe in the pill, but get you to bring pressure to bear on doctors.

Wouldn’t a big part of the problem be solved simply by requiring drug companies to release all their data?

There should be a law requiring them to reveal all the data. I think that’s a key thing: there should be access to all of the data from the clinical trials. We take risks with new pills on an understanding that the data is going to be made available to experts to sift through and let us all know what the true profiles of these pills are.

If people entering into trials were asked to sign form saying, ‘Do you agree to have pharmaceutical companies sequester the data from this trial?’ they wouldn’t have signed it. Most assumed that because it appears to be science, that the scientific community will get to scrutinize the trials.

You’re personally working on a project to help bring more of the risks to light.

What we’re trying to do with our colleagues is to open up patient adverse event reporting. It’s called rxrisk.org, which will be a website where both people on pills and their doctors can go to report adverse events that may be happening. The idea is to give you a tool so that if things are going wrong, you can get an expert report from us about what is known about the links between the problem and the pills you’re on and by asking a few questions, try to pinpoint whether the pill actually causing the problem. That will give you a report to take to your doctor to make it easier to overcome the kind of hostage problem most people have when they go to the doctor and want to keep him or her happy. The idea is ultimately to create teamwork between doctors and patients and let them know in real time how many other people have reported this problem also.

We’re trying to put patients and doctors in the kind of position where, if they know that thousands of others have had this problem and then the pharmaceutical company says there’s no linkage, people won’t believe it and will say, This isn’t right. It’s in beta at moment.

So what else can be done?

There are ways to play with the system to get the outcomes we want. At the moment, we have a system that works well for the health of pharmaceutical companies but not so well for our health. I’m just trying to raise these issues. How best we solve them is a different matter, but we can’t begin to try to solve them if we don’t raise them. I’m not hugely hopeful but not entirely pessimistic either.

See more of Healthland’s ‘Mind Reading’ series.

Maia Szalavitz is a health writer for TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland’Facebook page and on Twitter at @TIMEHealthland.

Read more: http://healthland.time.com/2012/03/28/mind-reading-psychiatrist-dr-david-healy-defines-pharmageddon/#ixzz2Jditsmvl

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Senza categoria

Gli antidepressivi come i placebo

SSRI

New Research on the Antidepressant-vs.-Placebo Debate

(Updated) In the 1990s, everyone was “Listening to Prozac,” after best-selling author Peter Kramer described sparkling personality transformations in patients who took the titular antidepressant drug. Then came the backlash: by the early 2000s, studies showed that Prozac and other selective serotonin reuptake inhibitors, or SSRIs, weren’t exactly miracle pills but were instead associated with suicide, especially in kids and teens. Another whiplash-inducing turn came in 2008, when a review of the research found that the drugs were actually no more effective than sugar pills, except in cases of the most severe depression.

Last month, research published in the Archives of General Psychiatry sought to help explain the paradoxical findings on SSRIs and other new generation antidepressant drugs, the increasingly popular medications that are now used by more than 1 in 10 Americans over 12. Using a new statistical approach, researchers led by Dr. John Krystal at Yale University School of Medicine reanalyzed data from seven clinical trials involving 2,515 patients, whose results were used to win FDA approval for the SNRI (a drug that affects both serotonin and norepinephrine) duloxetine (Cymbalta).

Known as growth-mixture modeling, the statistical technique allowed the authors to track how individual patients improved or worsened over time in response to medication or a placebo. The researchers found that roughly three-quarters of patients did better on medication than on a placebo. “That’s much more than half and half. That’s quite favorable,” says Krystal.

However, Krystal adds, just under a quarter of patients did not respond well to drug treatment and in fact did worse on antidepressants than did patients who were given a placebo.

MORE: Report: 1 in 5 American Adults Takes Mental Health Drugs

The benefit of growth-mixture modeling is that it reveals treatment trajectories of patients rather than looking at outcomes on average. When some patients get better while others get worse, the true impact of the drug may be “canceled out” in the data if they are considered only in the aggregate, obscuring both the drug’s harms and its benefits. That may help explain why some research finds that antidepressants work no better than a placebo.

“This has enormous implications for understanding the limits of the effectiveness of our current medications,” says Krystal. “These data really caution against the demonization of antidepressants as merely placebo, but they do raise a concern that some people are better off on placebo than on the antidepressant that they’re getting.”

Irving Kirsch, professor of psychology at the University of Hull in England and author of a 2008 meta-analysis in PLoS Medicine that found little benefit of antidepressants for most patients, is less sanguine about the new study. He characterizes the results as “indeed important” but says they suggest that “while many people may benefit from antidepressant treatment (although most of them to a degree that is not clinically significant), about 1 in 4 are made worse.”

“What makes this particularly problematic is the fact that we don’t know who these people are,” Kirsch says. “Although placebo may not be a viable treatment option, there are other treatments that on average work as well as antidepressants, [such as] physical exercise and cognitive behavioral psychotherapy. As far as we know, these alternatives don’t make people worse.

“This suggests to me that antidepressants should be kept as a last resort, and if a person does not respond to the treatment within a few weeks, it should be discontinued,” says Kirsch.

Krystal agrees that if one-quarter of patients with depression are made worse by antidepressant treatment, “we need to find ways to identify who those people are and find other ways to reach that group of people.”

MORE: Study Shows Antidepressants Affect Brain Differently than Placebo

Krystal’s study also found that people who improved on a placebo did so as quickly as those who improved with medication. This is important because it suggests that using a “washout period,” a technique used in some clinical trials to weed out placebo responders by eliminating participants who respond quickly, may not work with antidepressant studies.

“It counteracts the expectations that the field has that placebo response is fast and drug response is slow. Simply having a brief placebo-exposure period is not likely to eliminate the impact of placebo on outcome,” Krystal says.

That further complicates efforts to figure out the true effects and mechanism of antidepressant drugs. “We’re going to have to study people who are worse off on drug than placebo, and [not knowing who they are] will make it harder to determine whether there’s a statistically significant effect of the drug.” And given that it may be difficult to eliminate placebo responders simply through clever study design, questions about how antidepressants work, and in whom, may not be resolved until genetic or other tests can be devised to predict individual responses.

“This going to remain a challenge for study for some time,” concludes Krystal, whose latest study was funded by the government but who has received industry funding for other research.

MORE: Study: Stress-Depression Connection Sheds Light on Antidepressant Effects

A separate study published in the American Journal of Psychiatry (AJP) in December highlights other potential complications. The authors of that paper report that since 1980, the percentage of depressed patients responding to a placebo in clinical trials has risen by 7% per decade, reaching 50% in some studies.

Why? In the early years, participants for antidepressant trials were recruited from psychiatric hospitals, which meant that only the most severe cases were included. Today, however, participants are often recruited through advertisements and are paid to be in the trials. That introduces two problems that skew study populations: the most seriously depressed people often lack the capacity even to make a phone call in response to an ad and are thus overlooked, while other people may be persuaded to exaggerate symptoms of depression in order to participate in the trials and get the money. The authors of the AJP study report cases of “professional guinea pigs” who faked symptoms or enrolled in several trials at once.

Given the complexities of studying antidepressants — which appear to be placebos for some, poisons for others and miracle pills for yet others — it seems that data analysis in antidepressant research will likely remain a growth industry for decades to come. Until scientists can work it out, patients and psychiatrists will have to try multiple methods to treat depression until they hit on something that helps, keeping in mind that antidepressant drugs may backfire for some patients.

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Correction [Jan. 23, 2012]: The original version of this story mischaracterized Cymbalta as a selective serotonin reuptake inhibitor, or SSRI. The antidepressant drug is an SNRI, which affects both norepinephrine and serotonin.

Maia Szalavitz is a health writer for TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland‘s Facebook page and on Twitter at @TIMEHealthland.

Read more: http://healthland.time.com/2012/01/18/new-research-on-the-antidepressant-versus-placebo-debate/#ixzz2Jdn2N6Ft

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