Heroes Not Zombies

Here’s one of the most challenging and thought-provoking articles I’ve read for a long time. It’s by Sharon Begley and the title is “The Depressing News about Antidepressants”.   A lot of people take antidepressants and the consumption is increasing. In the US it’s doubled in a decade (from 13.3 million in 1996 to 27 million in 2005). Most of these people say the antidepressants help them (about 3 out of every 4 people say that).
However, researchers such as Irving Kirsch, of Hull University, have been looking closely at the evidence base to see how much of the benefit can be attributed to the drugs, and how much to the placebo effect.
In 1998 they reviewed 38 trials (all of which were sponsored by the manufacturers of the drugs) and found that in the 3000 patients studied, those who received placebo demonstrated about 75% of the improvement experienced by those on the drugs. Now you might think that means the drugs were more effective than the placebo, and that’s true, but how much more effective? One of the mistakes people often make when reading clinical trials is to assume that in the two groups, the placebo group and those taking the drug, that the placebo effect only occurs in the placebo group. That’s not true, however. The placebo effect occurs in everyone and the results of those trials suggest that three quarters of the improvement experienced by those taking the antidepressants is due to the placebo effect, and only a quarter to the actual drug.
Kirsch then went on to examine unpublished trials. He found that 40% of the trials of these drugs were unpublished (across the board an average of 22% of clinical trials are unpublished so this was an unusually high proportion). He found that in over half of the unpublished studies the drugs performed no better at all than placebo. This pushed the placebo effect in antidepressants up from 75% of the overall effect to 82%. The additional 18% difference was hardly clinically significant (amounting to only 1.8 point extra improvement in the 54 point depression rating scale)
In January this year, Hollon, DeRubeis and others published, in JAMA, their own review of clinical trials of antidepressants and concluded

“Most people don’t need an active drug,” says Vanderbilt’s Hollon, a coauthor of the study. “For a lot of folks, you’re going to do as well on a sugar pill or on conversations with your physicians as you will on medication. It doesn’t matter what you do; it’s just the fact that you’re doing something.” But people with very severe depression are different, he believes. “My personal view is the placebo effect gets you pretty far, but for those with very severe, more chronic conditions, it’s harder to knock down and placebos are less adequate,” “Prescribers, policy-makers, and consumers may not be aware that the efficacy of [antidepressants] largely has been established on the basis of studies that have included only those individuals with more severe forms of depression,” People with anything less than very severe depression “derive little specific pharmacological benefit from taking medications. Pending findings contrary to those reported here … efforts should be made to clarify to clinicians and prospective patients that … there is little evidence to suggest that [antidepressants] produce specific pharmacological benefit for the majority of patients.”

The Newsweek article goes on to consider the issues of using increasingly high doses of antidepressants and switching from drug to another, but nothing shakes the conclusion that by far and away the greatest effect of antidepressants is from the placebo effect. The author also considers the serotonin story showing that lowering brain levels of serotonin appears to have no effect on mood which makes it hard to swallow the theory that SSRIs (Serotonin Selective Reuptake Inhibitors), the most modern form of antidepressant, like Prozac, relieve depression by altering serotonin levels.
But wait! As Jonah Lehrer points out in his excellent post on this article, there is evidence that SSRIs might increase brain plasticity – in other words, maybe they make it easier for you to cope, so let’s not throw them away yet!

So, here’s the first disturbing part of this article – antidepressants are, for most people, not any more beneficial than placebos.
What’s the second issue?
What do we do about that?
A major theme of the article is the “moral dilemma” involved in sharing this knowledge. The point that Sharon Begley makes in this article is that we know the placebo effect is highly dependent on the patient’s expectations and beliefs about the treatment they are receiving (in other words, if you tell someone their treatment is “only” as good as placebo), then the benefit they were experiencing disappears (or at least reduces substantially).  Here’s the summary of the argument –

Friends and colleagues who believe Kirsch is right ask why he doesn’t just shut up, since publicizing the finding that the effectiveness of antidepressants is almost entirely due to people’s hopes and expectations will undermine that effectiveness. Kirsch, he insists that it is important to know that much of the benefit of antidepressants is a placebo effect. If placebos can make people better, then depression can be treated without drugs that come with serious side effects, not to mention costs. Wider recognition that antidepressants are a pharmaceutical version of the emperor’s new clothes, he says, might spur patients to try other treatments. “Isn’t it more important to know the truth?” he asks. Based on the impact of his work so far, it’s hard to avoid answering, “Not to many people.”

This dilemma is such a dilemma in part because the placebo response is so poorly understood, and, I believe mis-conceptualised (cripes! is there such a word?) In particular, many people make the erroneous assumption that a placebo is no better than doing nothing, and/or that it’s effects are only temporary, so not ultimately useful. Neither of these assumptions is justifiable. A benefit, or a harm, from a placebo, or nocebo, can be both powerful and long-lasting.
Kirsch has a new book out entitled “The Emperor’s New Drugs”. In the opening pages he includes this excellent graph.

What the graph shows so clearly is not only that the drug effect is not that much greater than the placebo effect, but that the placebo effect is considerably greater than doing nothing. I think this is a key point which is commonly missed, and which we need to address. If you think the placebo effect is no better than doing nothing, you’ll argue that any treatment which is not significantly greater in its effect than the placebo effect should be withdrawn. But then what? What if everyone who is currently taking antidepressants stopped them because they are no better than placebo? The amount of mental distress and harm would probably go through the roof. Kirsch is at pains to specifically warn against this response in the front of his book.

This is a complicated question. It’s not as simple as dividing treatments into those “which work” and those “which don’t work” on the basis of placebo controlled trials.
Don’t we need to approach this problem from a different angle? Human beings are complex adaptive organisms. Complex adaptive organisms self-organise. That’s a fundamental characteristic of all complex adaptive systems. Self-organisation in human beings includes defence and repair. There is no way for anyone to heal other than through the effective functioning of our self-organisation, or to put it another way, we only become well through the effects of self-healing. It doesn’t matter whether someone receives a drug or a placebo, if they are genuinely healing, it’s self-healing that’s doing it – in both cases. Drugs, at best, are adjuvants to that process. They support the organism as it self-heals.
The question then is what treatments support and promote self-healing? The second question is what potential harms can those treatments cause? A choice about treatment then involves balancing these two aspects – the potential for healing vs the potential for harm. As well as comparing treatment options this way,  we then need to set this against what we’d expect might happen if we did nothing.
I don’t think any of this is easy, and I certainly don’t think I’ve got it all worked out myself yet either, but isn’t it time we started to think about health care differently?

As I said at the start of this post, this is one of the most disturbing and thought-provoking articles I’ve read for a long time. (I’ve added The Emperor’s New Drugs to my reading list!)

Read Full Post »

BBC Radio 4’s Start the Week this week included Professor Steve Jones, the geneticist. He had something very interesting to say. (You can listen here, or download the podcast from itunes)

He was bemoaning the tendency of the media to run headlines like “Scientists discover the gene for……” and then fill in the blank with whatever physical or behavioural characteristic known to Man. He said very, very clearly that this was pretty much always hype. Even where there was a definite gene, say, for example, for bowel cancer in familial bowel cancer, it was only of relevance to members of families who had the familial pattern of bowel cancer, and meant nothing to everyone else who had bowel cancer. He pointed out that scientists have been unable to “find the gene” which determines height, despite the fact that adult height is strongly related to parental height.

Life, it turns out, is just not so simple. We cannot say, “there’s a gene for that…..” We can say “genetic factors influence……” but that’s really not the same thing at all.

John Cleese put the same point across – in my opinion more effectively, and had me laughing out loud – though I do think the way Steve Jones communicates is also strong, clear and enjoyable. Listen to the programme, and take two minutes to watch this video…..

Read Full Post »

The BBC recently broadcast a fabulous programme, “The Secret Life of Chaos”, presented by Prof Jim Al-Khalili. You can find it up on youtube just now, divided into 6 approximately 10 minute parts (I guess, in terms of copyright, it shouldn’t be there, so maybe it’ll disappear).
As well as being a great, crystal clear communication, it’s visually stunning, but the essence of the programme is how scientific discoveries have shown us that the old Newtonian model of “laws” which can be used to accurately predict the future and a universe which works like a giant clockwork really is not a good fit with reality. Over the course of the last hundred years scientists have begun to understand how a better model of the universe is the complex one. There are a couple of particular findings which have changed our view significantly. One is how in a complex system, a small change at the beginning can produce huge changes in the over all system (“the butterfly effect”) and the other is the amazing capacity of complex systems to self-organise.

Both of those findings have shown us that it isn’t possible to accurately know causes, and it isn’t possible to accurately predict outcomes.

Scientists who claim certainty, who with conviction of their own rightness, dismiss anyone who voices doubt or an alternative view, really aren’t up to speed. I like humble scientists who are enthralled by the complexity of reality. I don’t have much time for those who arrogantly claim they know all they need to know about something.

Take a look at this one clip from the programme – it’s the section where he discusses Belousov‘s findings. There are two elements to that story – the amazing, wonderful discovery he made, and the way he was totally dismissed by the ruling orthodoxy because his findings were “against the laws of physics”.

Interesting.

Read Full Post »

As I was walking to the station the other morning I noticed something weird about the digital clock on one of the buildings. I stopped and captured it using the video function of my digital camera. Then, just for fun, I imported it into imovie8 and plopped the opening bars of a Jimmy Nail song into the soundtrack.

Here it is……..weird, huh?

Read Full Post »

One of the key scenes in Le Petit Prince is where the little fox appears. The fox declines the little prince’s invitation to play saying “you are still nothing more than a little boy who is just like a hundred thousand other little boys. And I have no need of you. And you, on your part, have no need of me. To you, I am nothing more than a fox like a hundred thousand other foxes.” This is what it’s like on a busy commuter train or as you weave your way through a crowded city street. You come close to many people; you might sit right next to them for an hour or so; or you might buy a coffee in the cafe right after they do and sit at a neighbouring table; but you don’t know each other, mean nothing to each other, make no kind of connection.

The fox says “Apprivoise moi”. What does this mean? The direct English translation is “Tame me”, but taming in English suggest some subjugation, some domination, and that’s not what is meant by the fox. Instead he means something like “befriend me”, or “captivate me”, “bind yourself to me” or “make me yours”. It’s a loving expression and it conveys the idea of creating a link or a bond between two people, or between a person and a creature. The fox says that if the little prince does this he will make them unique to each other in the world. He will make them special to each other.

The little prince takes this idea and thinks about a bed of roses he comes across and how all of these roses really mean nothing to him compared to the single rose which he has nurtured carefully in his garden. His rose is uniquely his. He is bound to her. She is special to him.

Later, the little prince saw a garden of roses. “You are not at all like my rose,” he said. “As yet you are nothing. No one has befriended you, and you are no one’s friend. You are like my fox when I first knew him. He was only a fox like a hundred thousand other foxes. But I have made him my friend, and now he is unique in all the world… He went on. “To be sure, an ordinary passerby would think that my rose looked just like you. But in herself alone she is more important than all the hundreds of you other roses: because it is she that I have watered, because it is she that I have listened to, because she is my rose.”

It’s an interesting concept, isn’t it? How we create loving bonds between ourselves and others, and in so doing, make people (or animals) special to us, make them unique.

Read Full Post »