No Difference in Outcome between Antidepressants and Active Placebos?
đŽ WATCH THE FULL EPISODE: https://ept.ms/4k7AINXShow more Sixty years ago, studies were done comparing antidepressants with what is called âactive placebos,â drugs that mimic the side effects of antidepressants. The conclusion? Almost no difference in outcome.
Reading about the results of these 1960s studies was a lightbulb moment for British psychiatrist Dr. Joanna Moncrieff. She was a junior psychiatrist at the time working in a mental hospital in the UK, and she started looking into these studies when she didnât observe any obvious improvements in patients on antidepressants.
Larger and more developed trials conducted decades later likewise show such small differences between an antidepressant and a placebo that they do not qualify as a clinically meaningful difference, she says.
In 1998, psychologist Irving Kirsch published a widely publicized paper on this phenomenon called âThe Emperor's New Drugs.â
Psychiatry, she says, hasnât taken trial results seriously from many decades showing the ineffectiveness of antidepressants:
âWhy has psychiatry⊠not said: âOh dear, maybe we should stop giving out these drugs that are having minimal, if any, beneficial effects, and yet are causing side effects, making people dependent, giving people some really severe withdrawal problems, causing sexual dysfunction, making people have falls and bleeds, and causing fetal malformations and all the other things that antidepressants do.â
âInstead of questioning why we were prescribing these drugs so widely and trying to rein in the prescribing, leading psychiatric researchers found ways to present the evidence that made it look a little bit better,â she says. Show less
So at this point, I'm a junior, junior psychiatrist working in hospitals, doing what I'm told to do by the senior psychiatrists and trying to sort of square that with my views and my conscience.
And then I get some research positions, which enable me to do some research and in particular to look at some of the literature on drug treatment in more detail.
And that leads me to investigate the literature on antidepressants versus placebo.
Now, one of the more senior psychiatrists I worked with said to me once, I was saying to him, look, we're giving all these people antidepressants.
Some of them seem to get a bit better, but some of them don't.
They're probably getting better because they've got a new job or they've sorted out their relationship problems.
I'm not sure that I see any obvious benefit of these antidepressants.
And he said to me, oh, no, they're just active placebos.
Go and go and read this study published in the British Journal of Psychiatry, as it happened.
So I went off and read this study, and it was a description of some studies that had been done in the 1960s that compared antidepressants to what was called an active placebo, which was basically a drug that was not thought to be an antidepressant, but mimicked some of the side effects of antidepressants.
And those studies showed no difference between antidepressants and the active placebo.
And that was a real light bulb moment for me.
I thought, oh, yes, of course.
All these placebo-controlled trials where you use a dummy tablet that has no effect are not really measuring the full placebo effect of taking an actual drug that makes you feel a bit different, that gives you some side effects or just maybe just makes you feel as if you're in a slightly different mental state.
And of course, if you, you know, if you're in one of these trials and you think you've got the real drug because you're feeling a little bit different or you've got a dry mouth or you're feeling a bit sick, you're going to have a stronger placebo effect because you think you've got the real thing.
You've been told that you're in this trial to try out this brilliant new treatment that we've got for depression.
And so most people in that situation want the real drug and will get a boost if they think that's what they've got.
And I think that's what accounts for what is actually a very small difference between antidepressants and placebo in the clinical trials that are conducted of them.
So what happened with this study?
I mean, have people been trying to replicate it?
I mean, I haven't been studying this area for that long, but I know quite a number of psychiatrists who are deeply committed to helping people, which one would hope would be the case with most psychiatrists, actually.
And you're describing a study here that's basically saying there's no difference between placebo and SSRI with a whole bunch of side effects.
It kind of suggests an industry that doesn't have this type of care in mind.
I mean, how did we get here?
Yeah.
And not only that, not only do we have these studies that show no difference between antidepressants and placebo, which are quite old.
So, you know, could maybe be dismissed because they were all done back in the 60s and, you know, they've got various, you know, some of them were quite small, various limitations.
But the majority of data from placebo control trials shows very small differences between an antidepressant and a placebo, so small that they would not qualify as actually being a clinically meaningful difference.
And we've known that at least since 1998, when a psychologist called Irving Kirsch published a really widely publicized paper called The Emperor's New Drugs, in which he was saying, look, we're giving people all these drugs, but they don't actually do anything.
Why Psychiatry Ignores Small Differences00:02:05
So why has psychiatry not taken this seriously, not taken this on board, not said, oh dear, you know, maybe we should stop giving out these drugs that are having minimal, if any, beneficial effects and yet are, you know, causing side effects, making people dependent, giving some people really severe withdrawal problems, causing sexual dysfunction,
making people have falls and bleeds and causing fetal malformations and all the other things that antidepressants do.
So instead of doing that, instead of questioning why we were prescribing these drugs so widely and trying to rein in the prescribing, researchers, leading psychiatric researchers found ways to present the evidence that made it look a little bit better.
So they did things, well, first of all, they ignored the fact that there was this problem with the placebo effect and that people could probably work out whether they were getting the real placebo or not, the real drug or not.
Then they presented the data in a different way.
Instead of presenting the actual data that is collected from people, which consists of scores on depression rating scales.
Now, there are lots of questions, you know, sort of questions about whether a depression rating scale really measures depression.
You know, measuring depression is not like measuring blood pressure.
But just putting those aside for a minute, the actual data shows very small differences on these depression rating scale scores between the placebo and the antidepressant groups in these trials.
But if you draw a line through the data and you say people who get above this score will count as responders, people who get below this score will count as non-responders, that massively inflates the difference.
Because if you draw the line in the right place, you can make it look as if you've got a big difference.