Previously, I blogged about how the placebo effect is at work when you watch a horror movie. As part of my... research for this post I watched quite a lot of them. Here are my thoughts on some recent ones. Roughly in order of best to worst. Some minor spoilers, but nothing worse than you'd get from the trailer.
The Last Exorcism - Very scary, and full of surprises. The trailer makes it look like a shameless clone of The Exorcist; it isn't. Gets Neuroskeptic bonus points for the opening bit where the hero, a preacher who's lost his faith, talks about how he keeps doing "exorcisms" because it's psychologically helpful i.e. a placebo effect.
The Broken - Inventive, intelligent and creepy. A woman starts seeing her own doppelgänger after a car crash. Neuroskeptic bonus points for mentioning Capgras syndrome, a classic neurological disorder. Well worth watching.
The Signal - A mysterious TV glitch sends people crazy. But who's actually affected, and who's just been sent crazy by the fact that everyone else is going crazy around them? A clever twist on the zombie apocalypse genre, and manages to be both frightening and funny.
Carriers - An airborne Ebola virus wipes out almost everyone. Four teens try to escape. The characters and acting are pretty blah, but the concept is good, and it's well produced.
Dread - Student film-makers decide to make a documentary about people's worst fears, but one of them is a psychopath, so they end up making a Saw movie. Good, if a bit predictable.
The House of the Devil - An attempt at the kind of anticipation-horror that I talked about in my past post - nothing really happens, but the build-up is tense. Up to a point. Then it goes on for another half hour and gets tedious. Missable.
Tell Tale- Pretty standard slasher, except that the serial killer... is an internal organ! Actually not all that bad, but nothing special.
Mutants - Zombies attack survivors holed up in a hospital. In France. Extremely generic, there is no point in watching this if you've seen, well, any other zombie movie from the past 5 years.
Mulberry Street - "They're rat people, they're f-king rat people!" Some virus strikes New York, turning people into rat people. Who are also psychopaths. More funny than scary, unintentionally. Apparently this was done on basically zero budget: what's disappointing is that it comes across as quite polished despite that - the budget isn't the problem, the script is.
Previously, I blogged about how the placebo effect is at work when you watch a horror movie. As part of my... research for this post I watched quite a lot of them. Here are my thoughts on some recent ones. Roughly in order of best to worst. Some minor spoilers, but nothing worse than you'd get from the trailer.
The Last Exorcism - Very scary, and full of surprises. The trailer makes it look like a shameless clone of The Exorcist; it isn't. Gets Neuroskeptic bonus points for the opening bit where the hero, a preacher who's lost his faith, talks about how he keeps doing "exorcisms" because it's psychologically helpful i.e. a placebo effect.
The Broken - Inventive, intelligent and creepy. A woman starts seeing her own doppelgänger after a car crash. Neuroskeptic bonus points for mentioning Capgras syndrome, a classic neurological disorder. Well worth watching.
The Signal - A mysterious TV glitch sends people crazy. But who's actually affected, and who's just been sent crazy by the fact that everyone else is going crazy around them? A clever twist on the zombie apocalypse genre, and manages to be both frightening and funny.
Carriers - An airborne Ebola virus wipes out almost everyone. Four teens try to escape. The characters and acting are pretty blah, but the concept is good, and it's well produced.
Dread - Student film-makers decide to make a documentary about people's worst fears, but one of them is a psychopath, so they end up making a Saw movie. Good, if a bit predictable.
The House of the Devil - An attempt at the kind of anticipation-horror that I talked about in my past post - nothing really happens, but the build-up is tense. Up to a point. Then it goes on for another half hour and gets tedious. Missable.
Tell Tale- Pretty standard slasher, except that the serial killer... is an internal organ! Actually not all that bad, but nothing special.
Mutants - Zombies attack survivors holed up in a hospital. In France. Extremely generic, there is no point in watching this if you've seen, well, any other zombie movie from the past 5 years.
Mulberry Street - "They're rat people, they're f-king rat people!" Some virus strikes New York, turning people into rat people. Who are also psychopaths. More funny than scary, unintentionally. Apparently this was done on basically zero budget: what's disappointing is that it comes across as quite polished despite that - the budget isn't the problem, the script is.
The characters are going about their lives, blissfully unaware that something horrifying is about to happen. You the viewer know that things are going to end badly, though, because you know it's a horror movie.
Someone opens a closet - a bloody corpse could fall out!Or they're drinking a glass of water - which could be infected with a virus! Or they're talking to some guy - who's probably a serial killer!And so on.
The effect of this - and a good director can get a lot of mileage from it - is that scenes which would otherwise be entirely mundane, are experienced as scary, purely because you know that something scary is going to happen, so you see potential horror in every innocent little thing. An expectation as to what's going to happen, leads to you interpreting events in a certain way, and this creates certain emotions.
In a medical context, that would be called a placebo effect. Or a nocebo effect when expectations make people feel worse rather than better.
The horror movie analogy is useful, because it shows that placebo effects don't just happen to other people. We all like to think that if we were given a placebo treatment, we wouldn't be fooled. Unlike all those silly, suggestible, placebo responders, we'd stay as sick as ever until we got a proper cure.
I wouldn't be so sure. We're always interpreting the world around us, and interpreting our own thoughts and feelings, on the basis of our expectations and beliefs about what's going on. We don't suddenly stop doing this when it comes to health.
Suppose you have the flu. You feel terrible, and you're out of aspirin. You don't think you'll be able to make that meeting this afternoon, so you phone in sick.
Now, clearly, flu is a real disease, and it really does make you feel ill. But how do you know that you wouldn't be able to handle the meeting? Unless you have an extensive history of getting the flu in all its various forms, this is an interpretation, a best guess as to what you'll feel in the future, and it might be too pessimistic.
Maybe, if you tried, you'd get on OK. Maybe if you had some aspirin that would reassure you enough to give it a go. And just maybe it would still have worked even if those "aspirins" were just sugar pills... Link: See my previous posts I Feel X, Therefore Y and How Blind is Double Blind?
The characters are going about their lives, blissfully unaware that something horrifying is about to happen. You the viewer know that things are going to end badly, though, because you know it's a horror movie.
Someone opens a closet - a bloody corpse could fall out!Or they're drinking a glass of water - which could be infected with a virus! Or they're talking to some guy - who's probably a serial killer!And so on.
The effect of this - and a good director can get a lot of mileage from it - is that scenes which would otherwise be entirely mundane, are experienced as scary, purely because you know that something scary is going to happen, so you see potential horror in every innocent little thing. An expectation as to what's going to happen, leads to you interpreting events in a certain way, and this creates certain emotions.
In a medical context, that would be called a placebo effect. Or a nocebo effect when expectations make people feel worse rather than better.
The horror movie analogy is useful, because it shows that placebo effects don't just happen to other people. We all like to think that if we were given a placebo treatment, we wouldn't be fooled. Unlike all those silly, suggestible, placebo responders, we'd stay as sick as ever until we got a proper cure.
I wouldn't be so sure. We're always interpreting the world around us, and interpreting our own thoughts and feelings, on the basis of our expectations and beliefs about what's going on. We don't suddenly stop doing this when it comes to health.
Suppose you have the flu. You feel terrible, and you're out of aspirin. You don't think you'll be able to make that meeting this afternoon, so you phone in sick.
Now, clearly, flu is a real disease, and it really does make you feel ill. But how do you know that you wouldn't be able to handle the meeting? Unless you have an extensive history of getting the flu in all its various forms, this is an interpretation, a best guess as to what you'll feel in the future, and it might be too pessimistic.
Maybe, if you tried, you'd get on OK. Maybe if you had some aspirin that would reassure you enough to give it a go. And just maybe it would still have worked even if those "aspirins" were just sugar pills... Link: See my previous posts I Feel X, Therefore Y and How Blind is Double Blind?
Bear with me and I'll explain. It's less boring than it looks, trust me.
The Hamilton Scale (HAMD) is the most common system for rating the severity of depression. If you're only a bit down you get a low score, if you're extremely ill you get a high one. The maximum score's 52 but in practice it's extremely rare for someone to score more than 30.
First published in 1960, the HAMD is used in most depression research including almost all clinical trials of antidepressants. It's come under much criticism recently, but that's not the point here. The authors of the new paper, Kristen & von Wolff, simply asked: what does a given HAMD score mean in terms of severity?
It turns out that people have proposed no less than 5 different systems for interpreting HAMD scores. Do they all agree? Ha. Guess.
The pretty colors are mine. Just a glance shows a lot of variability, but the obvious outlier is the second one. That's the American Psychiatric Association (APA)'s official 2000 recommendations. Their interpretations of a given point on the scale tend to be worse than everyone else's.
This is most apparent at the top end. The APA use the terminology "Very Severe", which doesn't even appear on other scales. Much of what they class as "Very Severe" (23-26), two other scales class as "Moderate" depression! Amusingly, British authorities NICE seem to have been so unimpressed with this that they simply copied the APA's scale and toned everything down a notch for their 2009 criteria.
*
Why does this purely terminological debate matter? Well. A number of recent studies, most notoriously Kirsch et al (2008), have shown that antidepressants work better in more severe cases. See also my post here. The cut-off for antidepressants being substantially better than placebo generally comes out as about 26 on the HAMD in these studies.
Under the APA's 2000 terminology, this is well into the "Very Severe" band. Hence why Kirsch et al wrote - in a phrase that launched a thousand "Prozac Doesn't Work" headlines -
antidepressants reach... conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category.
But for Bech, 26 is simply middle-of-the-road "major depression". For Furukawa, it's borderline "moderate" or "severe". Hmm. So if they'd gone with those criteria, Kirsch et al would have written instead
antidepressants reach... conventional criteria for clinical significance only for patients with major depression, of moderate-to-severe severity.
All of these terminological criteria are arbitrary, so this isn't necessarily more accurate, but it's no less so. The irony of the fact that Kirsch et al used the American Psychiatric Associations own criteria to skewer modern psychiatry isn't lost on me and probably wasn't lost on them either.
*
But where did the APA get their system from? This is the most extraordinary thing. Here's the paper they based their approach on. It's an 1982 British study by Kearns et al. The authors wanted to see how the HAMD compared to other depression scales. So they used lots of scales on the same bunch of depressed patients and compared them to each other, and to their own judgments of severity. Here's what they found:
You'll recognize the APA's categories, kind of, but they're all shifted. Why? We can only guess. Here's my guess. The scores in that Kearns et al graph were the average HAMD scores of people who fell into each severity band. The APA must have decided that they could use these to create cutoffs for severity.
How? It's not at all clear. The mean score for "Moderate" was 18, but that's the topend of Moderate in the APA's book; ditto for "Mild". The average "Very Severe" was 30 and the average "Severe" was 21 so the cut-off should have been 25 or 26 if you just went for the midpoint, in fact the APA went with 23. And so on.
That's before we get into the question of whether you should be using these results to make cutoffs at all (you shouldn't.) And the APA seem to have ignored the fact that the HAMD did not statistically significantly distinguish between "Severe" and "Moderate" depression anyway (p=0.1). Kearns et al's graph shows that other scales, like the Melancholia Subscale ("MS"), would be better. But everyone's been using the HAMD for the past 50 years regardless.
In Summary: Interpreting the Hamilton Scale is a minefield of controversy and the HAMD is far from a perfect scale of depression. Yet almost everything we know about depression and its treatment relies on the HAMD. Don't believe everything you read.
Kriston, L., & von Wolff, A. (2010). Not as golden as standards should be: Interpretation of the Hamilton Rating Scale for Depression Journal of Affective Disorders DOI: 10.1016/j.jad.2010.07.011
Kearns, N., Cruickshank, C., McGuigan, K., Riley, S., Shaw, S., & Snaith, R. (1982). A comparison of depression rating scales The British Journal of Psychiatry, 141 (1), 45-49 DOI: 10.1192/bjp.141.1.45
Bear with me and I'll explain. It's less boring than it looks, trust me.
The Hamilton Scale (HAMD) is the most common system for rating the severity of depression. If you're only a bit down you get a low score, if you're extremely ill you get a high one. The maximum score's 52 but in practice it's extremely rare for someone to score more than 30.
First published in 1960, the HAMD is used in most depression research including almost all clinical trials of antidepressants. It's come under much criticism recently, but that's not the point here. The authors of the new paper, Kristen & von Wolff, simply asked: what does a given HAMD score mean in terms of severity?
It turns out that people have proposed no less than 5 different systems for interpreting HAMD scores. Do they all agree? Ha. Guess.
The pretty colors are mine. Just a glance shows a lot of variability, but the obvious outlier is the second one. That's the American Psychiatric Association (APA)'s official 2000 recommendations. Their interpretations of a given point on the scale tend to be worse than everyone else's.
This is most apparent at the top end. The APA use the terminology "Very Severe", which doesn't even appear on other scales. Much of what they class as "Very Severe" (23-26), two other scales class as "Moderate" depression! Amusingly, British authorities NICE seem to have been so unimpressed with this that they simply copied the APA's scale and toned everything down a notch for their 2009 criteria.
*
Why does this purely terminological debate matter? Well. A number of recent studies, most notoriously Kirsch et al (2008), have shown that antidepressants work better in more severe cases. See also my post here. The cut-off for antidepressants being substantially better than placebo generally comes out as about 26 on the HAMD in these studies.
Under the APA's 2000 terminology, this is well into the "Very Severe" band. Hence why Kirsch et al wrote - in a phrase that launched a thousand "Prozac Doesn't Work" headlines -
antidepressants reach... conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category.
But for Bech, 26 is simply middle-of-the-road "major depression". For Furukawa, it's borderline "moderate" or "severe". Hmm. So if they'd gone with those criteria, Kirsch et al would have written instead
antidepressants reach... conventional criteria for clinical significance only for patients with major depression, of moderate-to-severe severity.
All of these terminological criteria are arbitrary, so this isn't necessarily more accurate, but it's no less so. The irony of the fact that Kirsch et al used the American Psychiatric Associations own criteria to skewer modern psychiatry isn't lost on me and probably wasn't lost on them either.
*
But where did the APA get their system from? This is the most extraordinary thing. Here's the paper they based their approach on. It's an 1982 British study by Kearns et al. The authors wanted to see how the HAMD compared to other depression scales. So they used lots of scales on the same bunch of depressed patients and compared them to each other, and to their own judgments of severity. Here's what they found:
You'll recognize the APA's categories, kind of, but they're all shifted. Why? We can only guess. Here's my guess. The scores in that Kearns et al graph were the average HAMD scores of people who fell into each severity band. The APA must have decided that they could use these to create cutoffs for severity.
How? It's not at all clear. The mean score for "Moderate" was 18, but that's the topend of Moderate in the APA's book; ditto for "Mild". The average "Very Severe" was 30 and the average "Severe" was 21 so the cut-off should have been 25 or 26 if you just went for the midpoint, in fact the APA went with 23. And so on.
That's before we get into the question of whether you should be using these results to make cutoffs at all (you shouldn't.) And the APA seem to have ignored the fact that the HAMD did not statistically significantly distinguish between "Severe" and "Moderate" depression anyway (p=0.1). Kearns et al's graph shows that other scales, like the Melancholia Subscale ("MS"), would be better. But everyone's been using the HAMD for the past 50 years regardless.
In Summary: Interpreting the Hamilton Scale is a minefield of controversy and the HAMD is far from a perfect scale of depression. Yet almost everything we know about depression and its treatment relies on the HAMD. Don't believe everything you read.
Kriston, L., & von Wolff, A. (2010). Not as golden as standards should be: Interpretation of the Hamilton Rating Scale for Depression Journal of Affective Disorders DOI: 10.1016/j.jad.2010.07.011
Kearns, N., Cruickshank, C., McGuigan, K., Riley, S., Shaw, S., & Snaith, R. (1982). A comparison of depression rating scales The British Journal of Psychiatry, 141 (1), 45-49 DOI: 10.1192/bjp.141.1.45
I'm reading Le Rouge et le Noir ("The Red and the Black"), an 1830 French novel by Stendhal...
One passage in particular struck me. Stendhal is describing two characters who are falling in love (mostly); both are young, have lived all their lives in a backwater provincial town, and neither has been well educated.
In Paris, the nature of [her] attitude towards [him] would have very quickly become plain - but in Paris, love is an offspring of the novels. In three or four such novels, or even in a couplet or two of the kind of song they sing at the Gymnase, the young tutor and his shy mistress would have found a clear explanation of their relations with each other. Novels would have traced out a part for them to play, given them a model to imitate.
The idea that reading novels could change the way people fall in love might strange today, but remember that in 1830 the novel as we know it was still a fairly new invention, and was seen in conservative quarters as potentially dangerous. Stendhal was of course pro-novels (he was a novelist), but he accepts that they have a profound effect on the minds of readers.
Notice that his claim is not that novels create entirely new emotions. The two characters had feelings for each other despite never having read any. Novels suggest roles to play and models to follow: in other words, they provide interpretations as to what emotions mean and expectations as to what behaviours they lead to. You feel that, therefore you'll do this.
This bears on many things that I've written about recently. Take the active placebo phenomenon. This refers to cases in which a drug creates certain feelings, and the user interprets these feelings as meaning that "the drug is working", so they expect to improve, which leads them to feel better and behave as if they are getting better.
As I said at the time, active placebos are most often discussed in terms of drug side effects creating the expectation of improvement, but the same thing also happens with real drug effects. Valium (diazepam) produces a sensation of relaxation and reduces anxiety as a direct pharmacological effect but if someone takes it expecting to feel better, this will also drive improvement via expectation: the Valium is working, I can cope with this.
The same process can be harmful, though, and this may be even more common. The cognitive-behavioural theory of recurrent panic attacks is that they're caused by vicious cycles of feelings and expectations. Suppose someone feels a bit anxious, or notices their heart is racing a little. They could interpret that in various ways. They might write it off and ignore it, but they might conclude that they're about to have a panic attack.
If so, that's understandably going to make them more anxious, because panic is horrible. Anxiety causes adrenaline released, the heart beats ever faster etc., and this causes yet more anxiety until a full-blown panic attack occurs. The more often this happens, the more they come to fear even minor symptoms of physical arousal because they expect to suffer panic. Cognitive behavioural therapy for panic generally consists of breaking the cycle by changing interpretations, and by gradual exposure to physical symptoms and "panic-inducing" situations until they no longer cause the expectation of panic.
This also harks back to Ethan Watters' book Crazy Like Us which I praised a few months back. Watters argued that much mental illness is shaped by culture in the following way: culture tells us what to expect and how people behave when they feel distressed in certain ways, and thus channels distress into recognizable "syndromes" - a part to play, a model to imitate, though probably quite unconsciously. The most common syndromes in Western culture can be found in the DSM-IV, but this doesn't mean that they exist in the rest of the world.
Like Stendhal's, this theory does not attempt to explain everything - it assumes that there are fundamental feelings of distress - and I do not think that it explains the core symptoms of severe mental illness such as bipolar disorder and schizophrenia. But people with bipolar and schizophrenia have interpretations and expectations just like everyone else, and these may be very important in determining long-term prognosis. If you expect to be ill forever and never have a normal life, you probably won't.
I'm reading Le Rouge et le Noir ("The Red and the Black"), an 1830 French novel by Stendhal...
One passage in particular struck me. Stendhal is describing two characters who are falling in love (mostly); both are young, have lived all their lives in a backwater provincial town, and neither has been well educated.
In Paris, the nature of [her] attitude towards [him] would have very quickly become plain - but in Paris, love is an offspring of the novels. In three or four such novels, or even in a couplet or two of the kind of song they sing at the Gymnase, the young tutor and his shy mistress would have found a clear explanation of their relations with each other. Novels would have traced out a part for them to play, given them a model to imitate.
The idea that reading novels could change the way people fall in love might strange today, but remember that in 1830 the novel as we know it was still a fairly new invention, and was seen in conservative quarters as potentially dangerous. Stendhal was of course pro-novels (he was a novelist), but he accepts that they have a profound effect on the minds of readers.
Notice that his claim is not that novels create entirely new emotions. The two characters had feelings for each other despite never having read any. Novels suggest roles to play and models to follow: in other words, they provide interpretations as to what emotions mean and expectations as to what behaviours they lead to. You feel that, therefore you'll do this.
This bears on many things that I've written about recently. Take the active placebo phenomenon. This refers to cases in which a drug creates certain feelings, and the user interprets these feelings as meaning that "the drug is working", so they expect to improve, which leads them to feel better and behave as if they are getting better.
As I said at the time, active placebos are most often discussed in terms of drug side effects creating the expectation of improvement, but the same thing also happens with real drug effects. Valium (diazepam) produces a sensation of relaxation and reduces anxiety as a direct pharmacological effect but if someone takes it expecting to feel better, this will also drive improvement via expectation: the Valium is working, I can cope with this.
The same process can be harmful, though, and this may be even more common. The cognitive-behavioural theory of recurrent panic attacks is that they're caused by vicious cycles of feelings and expectations. Suppose someone feels a bit anxious, or notices their heart is racing a little. They could interpret that in various ways. They might write it off and ignore it, but they might conclude that they're about to have a panic attack.
If so, that's understandably going to make them more anxious, because panic is horrible. Anxiety causes adrenaline released, the heart beats ever faster etc., and this causes yet more anxiety until a full-blown panic attack occurs. The more often this happens, the more they come to fear even minor symptoms of physical arousal because they expect to suffer panic. Cognitive behavioural therapy for panic generally consists of breaking the cycle by changing interpretations, and by gradual exposure to physical symptoms and "panic-inducing" situations until they no longer cause the expectation of panic.
This also harks back to Ethan Watters' book Crazy Like Us which I praised a few months back. Watters argued that much mental illness is shaped by culture in the following way: culture tells us what to expect and how people behave when they feel distressed in certain ways, and thus channels distress into recognizable "syndromes" - a part to play, a model to imitate, though probably quite unconsciously. The most common syndromes in Western culture can be found in the DSM-IV, but this doesn't mean that they exist in the rest of the world.
Like Stendhal's, this theory does not attempt to explain everything - it assumes that there are fundamental feelings of distress - and I do not think that it explains the core symptoms of severe mental illness such as bipolar disorder and schizophrenia. But people with bipolar and schizophrenia have interpretations and expectations just like everyone else, and these may be very important in determining long-term prognosis. If you expect to be ill forever and never have a normal life, you probably won't.
An unexpected gem from last year's Journal of the American Psychoanalytic Association:Mind over medicine.
Surprisingly, it has nothing to do with psychoanalysis. Rutherford and colleagues performed a meta-analysis of lots of clinical trials of antidepressants. Neuroskeptic readers will be all too familiar with these. But they did an interesting thing with the data: they compared the benefits of antidepressants in trials with a placebo condition, vs. trials with no placebo arm, such as trials comparing one drug to another drug.
Why do that comparison? Because the placebo effect is likely to be stronger in trials with no placebo condition. If you volunteer for a placebo controlled trial, you'll know that you've got (say) a 50-50 chance of getting inactive sugar pills. You'll probably be uncertain whether or not you'll get better, maybe even quite worried. On the other hand if you're in a trial where you definitely will get a real drug, you can rest assured that you'll feel better - and that in itself might make your depression improve.
The paper only presents very preliminary results, but they say that:
Our group at Columbia has completed preliminary work involving metaanalyses of randomized controlled trials comparing antidepressant medications to a placebo or active comparator in geriatric outpatients with Major Depressive Disorder (Sneed et al. 2006). In placebo controlled trials, the medication response rate was 48% and the remission rate 33%, compared to a response rate of 62% and remission rate of 43% in the comparator trials (p < .05). The effect size for the comparison of response rate to medications in the comparator and placebo controlled trials was large (Cohen’s d = 1.2).
They only looked at trials of old age patients, but the same probably applies to everyone else.
Why does this matter? The authors suggest one very important implication. There are quite a few trials nowadays comparing the effects of psychotherapy, medication, neither, or both. How it works is that everyone gets pills, 50% of them real drugs and 50% placebos; also, half the people get psychotherapy while the others remain on the waiting list.
These trials often find that medication plus psychotherapy is better than just medication alone. This has led to the idea that therapy and drugs should be combined in clinical practice, a message which goes down really well, because it gives both psychopharmacologists and therapists the feeling that they have an important job to do. An example of this kind of trial is the influential TADS from 2004, finding that Prozac and therapy both work in depressed teens, and combining them is best. Everyone's a winner.
But as Rutherford et al. point out, there's a problem with this reasoning. The people who only get antidepressants don't know that they're getting any treatment, because they might be getting placebo. But the people who get antidepressants and therapy know that they're getting at least one real treatment (therapy). This is likely to improve their outcome through an expectation effect. (In fact, for some reason, in TADS, the people on combination treatment were told that they were getting both - they specifically knew they would never get dummy pills - which will have made this even worse.)
Now you could say that this doesn't matter: TADS and similar studies show that therapy and medication is better than just medication, and it's purely academic whether that's "just a placebo effect". But the key point is that in real life people always get medication knowing that it's real - so, like the therapy plus medication people in the trials, they get the benefit of the certainty that they are getting a real treatment. In the trials the medication-only group don't know that, but in real life they do - so the benefits of adding psychotherapy might be less, or even zero, in real life.
The authors of the TADS study did acknowledge this in their original paper, but only very briefly - here's all they say about it:
Blinding patients in the placebo and fluoxetine alone groups but not in the CBT alone group (participants knew they would not be receiving fluoxetine) and the fluoxetine combined with CBT group (participants knew that they would be receiving fluoxetine) may have interacted with expectancy effects regarding improvement and acceptability of treatment assignment.
Yet this limitation means they, strictly speaking, all TADS showed is that Prozac works in this group. It doesn't prove that adding (very expensive) therapy benefits anyone, in the real world. This is not to say that psychotherapy doesn't work of course, maybe it does, but the point is that therapy + medication trials may be best without a placebo.
Rutherford, B., Roose, S., & Sneed, J. (2009). Mind Over Medicine: the Influence of Expectations on Antidepressant Response Journal of the American Psychoanalytic Association, 57 (2), 456-460 DOI: 10.1177/00030651090570020909
An unexpected gem from last year's Journal of the American Psychoanalytic Association:Mind over medicine.
Surprisingly, it has nothing to do with psychoanalysis. Rutherford and colleagues performed a meta-analysis of lots of clinical trials of antidepressants. Neuroskeptic readers will be all too familiar with these. But they did an interesting thing with the data: they compared the benefits of antidepressants in trials with a placebo condition, vs. trials with no placebo arm, such as trials comparing one drug to another drug.
Why do that comparison? Because the placebo effect is likely to be stronger in trials with no placebo condition. If you volunteer for a placebo controlled trial, you'll know that you've got (say) a 50-50 chance of getting inactive sugar pills. You'll probably be uncertain whether or not you'll get better, maybe even quite worried. On the other hand if you're in a trial where you definitely will get a real drug, you can rest assured that you'll feel better - and that in itself might make your depression improve.
The paper only presents very preliminary results, but they say that:
Our group at Columbia has completed preliminary work involving metaanalyses of randomized controlled trials comparing antidepressant medications to a placebo or active comparator in geriatric outpatients with Major Depressive Disorder (Sneed et al. 2006). In placebo controlled trials, the medication response rate was 48% and the remission rate 33%, compared to a response rate of 62% and remission rate of 43% in the comparator trials (p < .05). The effect size for the comparison of response rate to medications in the comparator and placebo controlled trials was large (Cohen’s d = 1.2).
They only looked at trials of old age patients, but the same probably applies to everyone else.
Why does this matter? The authors suggest one very important implication. There are quite a few trials nowadays comparing the effects of psychotherapy, medication, neither, or both. How it works is that everyone gets pills, 50% of them real drugs and 50% placebos; also, half the people get psychotherapy while the others remain on the waiting list.
These trials often find that medication plus psychotherapy is better than just medication alone. This has led to the idea that therapy and drugs should be combined in clinical practice, a message which goes down really well, because it gives both psychopharmacologists and therapists the feeling that they have an important job to do. An example of this kind of trial is the influential TADS from 2004, finding that Prozac and therapy both work in depressed teens, and combining them is best. Everyone's a winner.
But as Rutherford et al. point out, there's a problem with this reasoning. The people who only get antidepressants don't know that they're getting any treatment, because they might be getting placebo. But the people who get antidepressants and therapy know that they're getting at least one real treatment (therapy). This is likely to improve their outcome through an expectation effect. (In fact, for some reason, in TADS, the people on combination treatment were told that they were getting both - they specifically knew they would never get dummy pills - which will have made this even worse.)
Now you could say that this doesn't matter: TADS and similar studies show that therapy and medication is better than just medication, and it's purely academic whether that's "just a placebo effect". But the key point is that in real life people always get medication knowing that it's real - so, like the therapy plus medication people in the trials, they get the benefit of the certainty that they are getting a real treatment. In the trials the medication-only group don't know that, but in real life they do - so the benefits of adding psychotherapy might be less, or even zero, in real life.
The authors of the TADS study did acknowledge this in their original paper, but only very briefly - here's all they say about it:
Blinding patients in the placebo and fluoxetine alone groups but not in the CBT alone group (participants knew they would not be receiving fluoxetine) and the fluoxetine combined with CBT group (participants knew that they would be receiving fluoxetine) may have interacted with expectancy effects regarding improvement and acceptability of treatment assignment.
Yet this limitation means they, strictly speaking, all TADS showed is that Prozac works in this group. It doesn't prove that adding (very expensive) therapy benefits anyone, in the real world. This is not to say that psychotherapy doesn't work of course, maybe it does, but the point is that therapy + medication trials may be best without a placebo.
Rutherford, B., Roose, S., & Sneed, J. (2009). Mind Over Medicine: the Influence of Expectations on Antidepressant Response Journal of the American Psychoanalytic Association, 57 (2), 456-460 DOI: 10.1177/00030651090570020909
There's a rather timely article in the current American Journal of Psychiatry: Assuring That Double-Blind Is Blind. Generally, when the list of the authors' conflicts of interest (550 words) is nearly as long as the text of the paper (740 words), it's not a good sign, but this one isn't bad. Perlis et al remind us that if you do a double-blind placebo controlled trial:
The blind may be compromised in a variety of ways, however, beginning with differences in medication taste or smell. Of particular concern may be the emergence of adverse effects, particularly when those adverse effects are known to be associated with a specific medication ... Indeed, when the degree of unblinding is assessed in antidepressant trials, multiple reports suggest that it is extensive: at least three-quarters of patients are typically able to correctly guess at their treatment assignment.
The point of a placebo-controlled trial is that neither the patients nor their doctors know whether they're getting the placebo or the real drug. Hence the strength of the placebo effect should be the same in each group, allowing the "real" drug effect to be measured.
But if the drug causes side effects, as pretty much all do, then people could work out which group they're in by noticing whether they're feeling side effects or not. This might enhance the placebo effect in the drug group, and make the drug seem to work better than it really does. Or it might not. But the possibility that it might is worrying.
This is called the active placebo effect. It's why I'm skeptical of claims that scopolamine and ketamine have rapid-acting but short lived antidepressant effects. I may be wrong, but while both of these drugs have been shown to work better than placebo, bothhave very pronounced subjective effects, so there's no chance the blind will have been intact.
Whether the active placebo effect also underlies the efficacy of established antidepressants like Prozac is very controversial. There have been 9 trials comparing antidepressants to active placebos, i.e. drugs that have similar side effects to antidepressants and that should therefore help to preserve the blind. (The active placebos were all atropine which is basically the same as scopolamine.)
The trials were reviewed by antidepressant critic Joanna Moncrieff et al who found that the overall effect size of antidepressants vs. active placebos was d = 0.39. That's not very high, although it's not too bad, and ironically it's actually higher than the effect that Moncrieff's friend and fellow Prozac-baiter Irving Kirsch found in his famous 2008 antidepressant vs. sugar pill placebo meta-analysis, d=0.32. So if you take that seriously, the active placebo effect plays no part in antidepressant efficacy. However the active placebo trials are mostly small and old, so to be honest, we don't really know.
*
A point that's often overlooked is that a drug could have an active placebo effect via having a "real" psychoactive treatment effect. Diazepam (Valium), for example, has basically no peripheral side effects at all: unlike scopolamine it doesn't cause dry mouth, nausea, etc. But it is a tranquillizer; it causes calmness and, at higher doses, sleep. They're pretty noticeable. So if you were to give a depressed person Valium and tell them that it's not only a tranquillizer, it's an antidepressant, then the active placebo problem would arise.
In fact, any active drug will also produce active placebo effects - almost by definition, if you think about it. These may be hard to disentangle from the "real" effects. Say you're anxious about giving a speech so you take some diazepam hoping to feel calmer. A short while later you feel the lovely warm tranquillizing feeling setting in. Phew, you're calm now, anxiety's gone, the speech will be no worry. That thought might well be tranquillizing in itself. In other words the anti-anxiety effects of diazepam are partially driven by active placebo responses due to... the anti-anxiety effects of diazepam.
*
This leads onto another point. Suppose a drug has a genuine effect which improves some of the symptoms of a disease. Does that drug "treat" that disease? In a weak sense, yes, and it might be a helpful drug, but it's not a specific treatment. Morphine's very helpful in cancer, because it treats pain, but it doesn't cure cancer. Likewise insomnia is a symptom of depression, but we feel that in order to qualify as an antidepressant a drug has to treat the core symptoms: mood, anxiety, etc. rather than just being a sleeping pill.
But suppose someone suffered from low mood and you gave them a treatment which stopped them feeling any moods or emotions. That solves their low mood problem: no mood, no problem. But is that a specific treatment for depression? It's a bit of a grey area, but many would say no.
Many people say that this is exactly what SSRI antidepressants do: they blunt your emotions. That doesn't mean they're not helpful in depression: a lot of people find them very useful. I did. But then are they really "antidepressants", or just anti-mood? SSRIs are the drugs of choice not just for depression but also most anxiety disorders, and obsessive-compulsive disorder, etc. In fact they work better in OCD than they do in depression, relative to placebo. So are SSRIs actually antiobsessives that happen to be helpful in some cases of depression? Good question.
Here's Chris Rock on the issue of non-specific effects...
*
Perhaps an ideal clinical trial of a drug for a psychiatric condition should have 4 groups: the drug you're studying, another psychotropic with non-specific effects (e.g. Valium, or caffeine if you want a stimulant), an active placebo with purely peripheral side effects, and sugar pills. But even then, if the active drug performed better than the other 3 groups, a die-hard skeptic could say that maybe it's just more effectively causingnon-specific sedation, or blunting, or whatever, than the Valium. Ultimately, a randomized controlled trial can never prove that a psychotropic drug has a specific as opposed to a non-specific effect.
So where do we stand? Does that mean we don't know what drugs do? No - unless we're some cloistered soul who only reads papers as opposed to talking to people, reading subjective reports, or taking drugs themselves. I know what alcohol does, not because I've read papers about it, but because I've drunk it. I've also been depressed and taken antidepressants, and for what it's worth, in my experience, some of the drugs currently marketed as antidepressants do have a specific anti-depression effect, although others don't. Overall, though, my view is that we know surprisingly little about what antidepressants actually do.
Perlis RH, Ostacher M, Fava M, Nierenberg AA, Sachs GS, & Rosenbaum JF (2010). Assuring that double-blind is blind. The American journal of psychiatry, 167 (3), 250-2 PMID: 20194487
Moncrieff J, Wessely S, & Hardy R (2004). Active placebos versus antidepressants for depression. Cochrane database of systematic reviews (Online) (1) PMID: 14974002
There's a rather timely article in the current American Journal of Psychiatry: Assuring That Double-Blind Is Blind. Generally, when the list of the authors' conflicts of interest (550 words) is nearly as long as the text of the paper (740 words), it's not a good sign, but this one isn't bad. Perlis et al remind us that if you do a double-blind placebo controlled trial:
The blind may be compromised in a variety of ways, however, beginning with differences in medication taste or smell. Of particular concern may be the emergence of adverse effects, particularly when those adverse effects are known to be associated with a specific medication ... Indeed, when the degree of unblinding is assessed in antidepressant trials, multiple reports suggest that it is extensive: at least three-quarters of patients are typically able to correctly guess at their treatment assignment.
The point of a placebo-controlled trial is that neither the patients nor their doctors know whether they're getting the placebo or the real drug. Hence the strength of the placebo effect should be the same in each group, allowing the "real" drug effect to be measured.
But if the drug causes side effects, as pretty much all do, then people could work out which group they're in by noticing whether they're feeling side effects or not. This might enhance the placebo effect in the drug group, and make the drug seem to work better than it really does. Or it might not. But the possibility that it might is worrying.
This is called the active placebo effect. It's why I'm skeptical of claims that scopolamine and ketamine have rapid-acting but short lived antidepressant effects. I may be wrong, but while both of these drugs have been shown to work better than placebo, bothhave very pronounced subjective effects, so there's no chance the blind will have been intact.
Whether the active placebo effect also underlies the efficacy of established antidepressants like Prozac is very controversial. There have been 9 trials comparing antidepressants to active placebos, i.e. drugs that have similar side effects to antidepressants and that should therefore help to preserve the blind. (The active placebos were all atropine which is basically the same as scopolamine.)
The trials were reviewed by antidepressant critic Joanna Moncrieff et al who found that the overall effect size of antidepressants vs. active placebos was d = 0.39. That's not very high, although it's not too bad, and ironically it's actually higher than the effect that Moncrieff's friend and fellow Prozac-baiter Irving Kirsch found in his famous 2008 antidepressant vs. sugar pill placebo meta-analysis, d=0.32. So if you take that seriously, the active placebo effect plays no part in antidepressant efficacy. However the active placebo trials are mostly small and old, so to be honest, we don't really know.
*
A point that's often overlooked is that a drug could have an active placebo effect via having a "real" psychoactive treatment effect. Diazepam (Valium), for example, has basically no peripheral side effects at all: unlike scopolamine it doesn't cause dry mouth, nausea, etc. But it is a tranquillizer; it causes calmness and, at higher doses, sleep. They're pretty noticeable. So if you were to give a depressed person Valium and tell them that it's not only a tranquillizer, it's an antidepressant, then the active placebo problem would arise.
In fact, any active drug will also produce active placebo effects - almost by definition, if you think about it. These may be hard to disentangle from the "real" effects. Say you're anxious about giving a speech so you take some diazepam hoping to feel calmer. A short while later you feel the lovely warm tranquillizing feeling setting in. Phew, you're calm now, anxiety's gone, the speech will be no worry. That thought might well be tranquillizing in itself. In other words the anti-anxiety effects of diazepam are partially driven by active placebo responses due to... the anti-anxiety effects of diazepam.
*
This leads onto another point. Suppose a drug has a genuine effect which improves some of the symptoms of a disease. Does that drug "treat" that disease? In a weak sense, yes, and it might be a helpful drug, but it's not a specific treatment. Morphine's very helpful in cancer, because it treats pain, but it doesn't cure cancer. Likewise insomnia is a symptom of depression, but we feel that in order to qualify as an antidepressant a drug has to treat the core symptoms: mood, anxiety, etc. rather than just being a sleeping pill.
But suppose someone suffered from low mood and you gave them a treatment which stopped them feeling any moods or emotions. That solves their low mood problem: no mood, no problem. But is that a specific treatment for depression? It's a bit of a grey area, but many would say no.
Many people say that this is exactly what SSRI antidepressants do: they blunt your emotions. That doesn't mean they're not helpful in depression: a lot of people find them very useful. I did. But then are they really "antidepressants", or just anti-mood? SSRIs are the drugs of choice not just for depression but also most anxiety disorders, and obsessive-compulsive disorder, etc. In fact they work better in OCD than they do in depression, relative to placebo. So are SSRIs actually antiobsessives that happen to be helpful in some cases of depression? Good question.
Here's Chris Rock on the issue of non-specific effects...
*
Perhaps an ideal clinical trial of a drug for a psychiatric condition should have 4 groups: the drug you're studying, another psychotropic with non-specific effects (e.g. Valium, or caffeine if you want a stimulant), an active placebo with purely peripheral side effects, and sugar pills. But even then, if the active drug performed better than the other 3 groups, a die-hard skeptic could say that maybe it's just more effectively causingnon-specific sedation, or blunting, or whatever, than the Valium. Ultimately, a randomized controlled trial can never prove that a psychotropic drug has a specific as opposed to a non-specific effect.
So where do we stand? Does that mean we don't know what drugs do? No - unless we're some cloistered soul who only reads papers as opposed to talking to people, reading subjective reports, or taking drugs themselves. I know what alcohol does, not because I've read papers about it, but because I've drunk it. I've also been depressed and taken antidepressants, and for what it's worth, in my experience, some of the drugs currently marketed as antidepressants do have a specific anti-depression effect, although others don't. Overall, though, my view is that we know surprisingly little about what antidepressants actually do.
Perlis RH, Ostacher M, Fava M, Nierenberg AA, Sachs GS, & Rosenbaum JF (2010). Assuring that double-blind is blind. The American journal of psychiatry, 167 (3), 250-2 PMID: 20194487
Moncrieff J, Wessely S, & Hardy R (2004). Active placebos versus antidepressants for depression. Cochrane database of systematic reviews (Online) (1) PMID: 14974002
Imagine there was a nasty disease that affected 1 in 100 people. And imagine that someone invented a drug which treated it reasonably well. Good work, surely.
Now imagine that, for some reason, people decided that 10% of the population need to be taking this drug, instead of 1%. So sales of the drug sky-rocket. Eventually some clever person comes along and asks "This is one of the biggest selling drugs in the world - but does it work?" They look into it, and find that it doesn't work very well at all. For about 9 out of 10 people, it's completely useless! What a crap drug.
Of course the drug hasn't changed, and what's crap was the decision to prescribe it to so many people.
*
Back to reality. According to accepted DSM-IV diagnostic criteria, close to 50% of people suffer from a mental illness at some point; a large fraction of this being depression. 10% of Americans took antidepressants last year according to the best estimates.
Guess what? Clever people have started asking "Antidepressants are amongst the biggest selling drugs in the world - but do they work?"And their answer is - not very well. The latest such claim came from Fournier et al and appeared in JAMA a couple of weeks ago: Antidepressant Drug Effects and Depression Severity.
These researchers re-analysed the data from six clinical trials testing antidepressants against placebo pills. The drugs were the tricyclic imipramine and the newer SSRI paroxetine. The total sample size was a respectable 718, and most trials lasted 8 weeks, which is longer than average for this kind of study. Here's what they found -
Grey circles are people on antidepressants, white circles people on placebo. What this shows is that the more severe the patient's depression, the more they get better - when they're given either drugs or placebos. However, because the improvement on antidepressants rises more steeply, the benefit of antidepressants versus placebos correlates with severity. The thin blue line marks the minimum severity for which the average effect of the drugs over placebo was "clinically significant" according to NICE criteria (although these are arbitrary).
*
So, this study says that antidepressants work better in more severe depression. This is not a new claim - Kirsch et al (2008) famously found the same thing, and long before that so did Khan et al (2002). However this new analysis has some advantages over previous ones. First, Fournier et al looked at what happened to each patient individually, whereas the previous studies found that in trials where the patients were more severely depressed, on average, antidepressants worked better.
Second, the patients in this analysis spanned a wide range of severity scores, from 10 points on the Hamilton Scale to nearly 40. In Kirsch et al almost all the trials had average severities in the narrow range of 22 to 29. Finally, none of the trials in the new paper used a placebo run-in period. These are meant to exclude people from the trial if they improve "too well" during an initial week or so of placebo pills. In theory, they bias trials against finding large placebo effects; it's not clear they actually work, but either way, it's good to know it wasn't a factor.
*
Overall, the evidence all seems to point to the idea that people with more serious clinical depression respond better to antidepressants vs. placebos in clinical trials. The exact details are debatable, there's the issue of whether antidepressant clinical trials are realistic, and the question of how clinically effective antidepressants are is also controversial, but I'm not aware of any studies which have contradicted this central claim.
But when you start to think about it, this is a very odd result. Fournier et al say that
The general pattern of results reported in this work is not surprising. As early as the 1950s, researchers conducting controlled investigations of treatments for a wide variety of medical and psychiatric conditions described a phenomenon whereby patients with higher levels of severity showed greater differential (i.e., specific) benefit from the active treatments.
and refer to a couple of papers from the 1960s. But I must admit that I do find this very surprising. We don't wait until someone's nearly dead from a bacterial infection before we give them antibiotics, we give them early, when the disease is still mild. Doctors unfortunately don't tell people "Good news! You've got advanced-stage cancer - just the kind where drugs work best." Why is depression so different?
Look a little closer, and a possible answer emerges. Severity, in all of these studies, was measured using the Hamilton Rating Scale for Depression (HAMD). The HAMD has 17 items, and each asks whether you're suffering from certain symptoms; the more symptoms you have, and the more pronounced they are, the higher your total score. You get 1 point if you have "occasional difficulty falling asleep", 2 points for "nightly difficulty falling asleep", 4 points for "Hand wringing, nail biting, hair-pulling, biting of lips". Here's the whole thing.
The HAMD was designed in 1960 by a psychiatrist, Max Hamilton, and it was originally intended for use by staff at psychiatric hospitals for use on depressed inpatients. So it's not a measure of severity per se: it's a measure of how well your symptoms match those considered to be characteristic of severe depression in 1960.
Psychiatry's concept of depression - not to mention the wider culture's - has changed greatly since then. 1960 was a full 20 years before the DSM-III criteria of depression were published, which form the basis for today's DSM-IV criteria. A quick comparison of the DSM-IV alongside the HAMD reveals a lot of differences. It's quite possible to meet DSM-IV criteria for "Major Depressive Disorder" yet score low on the HAMD.
Which brings us back to the imaginary scenario at the start of this post. My personal interpretation of results like those of Fournier et al is this: antidepressants treat classical clinical depression, of the kind that psychiatrists in 1960 would have recognized. This is the kind of depression that they were originally used for, after all, because the first antidepressants arrived in 1953, and modern antidepressants like Prozac target the same neurotransmitter systems.
Yet in recent years "clinical depression" has become a much broader term. Many people attribute this to marketing on the part of pharmaceutical companies. Whatever the cause, it's almost certain that many people are now being prescribed antidepressants for emotional and personal issues which wouldn't have been considered medical illnesses until quite recently. (Antidepressants also have a long history of use for other conditions, like OCD, but this is a separate issue.)
My imaginary story used made up numbers: I'm not saying that only 10% of the people on antidepressants have "classic" depression. I don't know what the % is. But apart from that, in my opinion (and I don't think I'm alone), it's far from fantasy.
Fournier, J., DeRubeis, R., Hollon, S., Dimidjian, S., Amsterdam, J., Shelton, R., & Fawcett, J. (2010). Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis JAMA: The Journal of the American Medical Association, 303 (1), 47-53 DOI: 10.1001/jama.2009.1943
Imagine there was a nasty disease that affected 1 in 100 people. And imagine that someone invented a drug which treated it reasonably well. Good work, surely.
Now imagine that, for some reason, people decided that 10% of the population need to be taking this drug, instead of 1%. So sales of the drug sky-rocket. Eventually some clever person comes along and asks "This is one of the biggest selling drugs in the world - but does it work?" They look into it, and find that it doesn't work very well at all. For about 9 out of 10 people, it's completely useless! What a crap drug.
Of course the drug hasn't changed, and what's crap was the decision to prescribe it to so many people.
*
Back to reality. According to accepted DSM-IV diagnostic criteria, close to 50% of people suffer from a mental illness at some point; a large fraction of this being depression. 10% of Americans took antidepressants last year according to the best estimates.
Guess what? Clever people have started asking "Antidepressants are amongst the biggest selling drugs in the world - but do they work?"And their answer is - not very well. The latest such claim came from Fournier et al and appeared in JAMA a couple of weeks ago: Antidepressant Drug Effects and Depression Severity.
These researchers re-analysed the data from six clinical trials testing antidepressants against placebo pills. The drugs were the tricyclic imipramine and the newer SSRI paroxetine. The total sample size was a respectable 718, and most trials lasted 8 weeks, which is longer than average for this kind of study. Here's what they found -
Grey circles are people on antidepressants, white circles people on placebo. What this shows is that the more severe the patient's depression, the more they get better - when they're given either drugs or placebos. However, because the improvement on antidepressants rises more steeply, the benefit of antidepressants versus placebos correlates with severity. The thin blue line marks the minimum severity for which the average effect of the drugs over placebo was "clinically significant" according to NICE criteria (although these are arbitrary).
*
So, this study says that antidepressants work better in more severe depression. This is not a new claim - Kirsch et al (2008) famously found the same thing, and long before that so did Khan et al (2002). However this new analysis has some advantages over previous ones. First, Fournier et al looked at what happened to each patient individually, whereas the previous studies found that in trials where the patients were more severely depressed, on average, antidepressants worked better.
Second, the patients in this analysis spanned a wide range of severity scores, from 10 points on the Hamilton Scale to nearly 40. In Kirsch et al almost all the trials had average severities in the narrow range of 22 to 29. Finally, none of the trials in the new paper used a placebo run-in period. These are meant to exclude people from the trial if they improve "too well" during an initial week or so of placebo pills. In theory, they bias trials against finding large placebo effects; it's not clear they actually work, but either way, it's good to know it wasn't a factor.
*
Overall, the evidence all seems to point to the idea that people with more serious clinical depression respond better to antidepressants vs. placebos in clinical trials. The exact details are debatable, there's the issue of whether antidepressant clinical trials are realistic, and the question of how clinically effective antidepressants are is also controversial, but I'm not aware of any studies which have contradicted this central claim.
But when you start to think about it, this is a very odd result. Fournier et al say that
The general pattern of results reported in this work is not surprising. As early as the 1950s, researchers conducting controlled investigations of treatments for a wide variety of medical and psychiatric conditions described a phenomenon whereby patients with higher levels of severity showed greater differential (i.e., specific) benefit from the active treatments.
and refer to a couple of papers from the 1960s. But I must admit that I do find this very surprising. We don't wait until someone's nearly dead from a bacterial infection before we give them antibiotics, we give them early, when the disease is still mild. Doctors unfortunately don't tell people "Good news! You've got advanced-stage cancer - just the kind where drugs work best." Why is depression so different?
Look a little closer, and a possible answer emerges. Severity, in all of these studies, was measured using the Hamilton Rating Scale for Depression (HAMD). The HAMD has 17 items, and each asks whether you're suffering from certain symptoms; the more symptoms you have, and the more pronounced they are, the higher your total score. You get 1 point if you have "occasional difficulty falling asleep", 2 points for "nightly difficulty falling asleep", 4 points for "Hand wringing, nail biting, hair-pulling, biting of lips". Here's the whole thing.
The HAMD was designed in 1960 by a psychiatrist, Max Hamilton, and it was originally intended for use by staff at psychiatric hospitals for use on depressed inpatients. So it's not a measure of severity per se: it's a measure of how well your symptoms match those considered to be characteristic of severe depression in 1960.
Psychiatry's concept of depression - not to mention the wider culture's - has changed greatly since then. 1960 was a full 20 years before the DSM-III criteria of depression were published, which form the basis for today's DSM-IV criteria. A quick comparison of the DSM-IV alongside the HAMD reveals a lot of differences. It's quite possible to meet DSM-IV criteria for "Major Depressive Disorder" yet score low on the HAMD.
Which brings us back to the imaginary scenario at the start of this post. My personal interpretation of results like those of Fournier et al is this: antidepressants treat classical clinical depression, of the kind that psychiatrists in 1960 would have recognized. This is the kind of depression that they were originally used for, after all, because the first antidepressants arrived in 1953, and modern antidepressants like Prozac target the same neurotransmitter systems.
Yet in recent years "clinical depression" has become a much broader term. Many people attribute this to marketing on the part of pharmaceutical companies. Whatever the cause, it's almost certain that many people are now being prescribed antidepressants for emotional and personal issues which wouldn't have been considered medical illnesses until quite recently. (Antidepressants also have a long history of use for other conditions, like OCD, but this is a separate issue.)
My imaginary story used made up numbers: I'm not saying that only 10% of the people on antidepressants have "classic" depression. I don't know what the % is. But apart from that, in my opinion (and I don't think I'm alone), it's far from fantasy.
Fournier, J., DeRubeis, R., Hollon, S., Dimidjian, S., Amsterdam, J., Shelton, R., & Fawcett, J. (2010). Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis JAMA: The Journal of the American Medical Association, 303 (1), 47-53 DOI: 10.1001/jama.2009.1943
