Bad Science - Washing the numbers, selling the model

[hypnagogue]

Similarly, quacks from the $600 billion pharma industry sell the idea that depression is caused by low serotonin levels in the brain and so – therefore - you need drugs which raise the serotonin levels in your brain: you need SSRI antidepressants, which are “selective serotonin reuptake inhibitors”.

That’s the serotonin hypothesis. It was always shaky, and the evidence now is hugely contradictory. I’m not giving that lecture here, but as a brief illustration, there is a drug called tianeptine – a selective serotonin reuptake enhancer, not an inhibitor – and yet research shows this drug is a pretty effective treatment for depression too.

Meanwhile in popular culture the depression/serotonin theory is proven and absolute, because it was never about research, or theory, it was about marketing, and journalists who pride themselves on never pushing pills or the hegemony will still blindly push the model until the cows come home. Which brings us on to our second new study on antidepressants. Two academics, a lecturer and an associate professor of neuroanatomy, decided to chase journalists, in the style of this column - or rather, in the style of this column on crack - and fired off multiple emails, demanding unrealistic levels of referencing from doubtless irritated and baffled hacks. They proudly document their work with an excessive number of examples, and I will pick just a few.

http://www.badscience.net/?p=607

 

[Ivan Seeking]

About twelve years ago, when I found myself depressed to the point of incapacitation, and after jumping through a bunch of hoops for the doctor, I was put on Prozac. After about six months I didn't like the effect that it was having so I stopped taking it. I then discovered that in order to control the depression, all that was really needed was to control my allergies.

Once again I went through a bunch of crap for nothing; the doctor got it wrong, and I was put on a drug that I didn't need.

 

[Moonbear]

From the above link:

Meanwhile, 22 studies that had negative or iffy results were simply not published at all, and 11 were written up and published in a way that described them as having a positive outcome.

What I would like to know is, did they ATTEMPT to publish those studies? There's a difference between not getting them published and not trying to get them published. There is a bias among reviewers/editors of journals that makes it very difficult to get negative results published, although you'd think it was in the best interest of science to make these studies known. They can get published, but it seems that they hold such papers to higher standards than ones that show positive effects, which is completely contrary to the way I think things should work.

I have similar concerns as that article raises when it comes to the depression literature, or more accurately, the anti-depressant literature. It was several years ago that I heard a talk by someone researching dopamine in depression, and he kept referring to this novel compound as an antidepressant, but the behavioral tests he was using, while fairly standard models, left me a bit baffled as to how they measured anti-depressant effects. So, I finally just asked. The rather disconcerting response is that they are the tests that have positive responses to current anti-depressants. In other words, they don't measure whether something is an anti-depressant, per se, but rather whether something affects some of the same systems as anti-depressants. For all they know, those could all be side effects they are measuring on other dopaminergic systems.

It's a field with an interesting history. I wouldn't brand them as quacks though. It's more that they found drugs with certain known effects that work in treating depression and then an entire field of research sprung up from it trying to figure out how and why these drugs work. It's the reverse of the direction research usually operates in, in which we have a known disease or disorder, try to understand the mechanism responsible for that disease or disorder, and then based on that knowledge, target new drugs to correct that problem.

That’s the serotonin hypothesis. It was always shaky, and the evidence now is hugely contradictory. I’m not giving that lecture here, but as a brief illustration, there is a drug called tianeptine – a selective serotonin reuptake enhancer, not an inhibitor – and yet research shows this drug is a pretty effective treatment for depression too.

This isn't so surprising, and doesn't necessarily disprove anything. There appear to be multiple causes of depression, and that's all that such a finding would support at this time (I thought this was understood by the general public as well, though the gist of the article seems to be that this is not so well known outside of scientific circles).

 

[Moonbear]

About twelve years ago, when I found myself depressed to the point of incapacitation, and after jumping through a bunch of hoops for the doctor, I was put on Prozac. After about six months I didn't like the effect that it was having so I stopped taking it. I then discovered that in order to control the depression, all that was really needed was to control my allergies.

Once again I went through a bunch of crap for nothing; the doctor got it wrong, and I was put on a drug that I didn't need.

This is a problem that is tough to overcome. Too many physicians have been trained to see depression as the disorder rather than as a symptom of another disorder and are quick to put patients on antidepressants and mask the real cause before fully investigating what else could be going on first.

 

[hypnagogue]

What I would like to know is, did they ATTEMPT to publish those studies?

Outlook is hazy.

http://content.nejm.org/cgi/content/abstract/358/3/252

We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both.

My guess is that they didn't attempt to get them published. That in itself isn't an indictment as it seems pretty commonplace even among academics that you only bother trying to get published if you get an effect in the first place. But I can imagine that the motives might be different if there is money on the line in addition to all other considerations.

This isn't so surprising, and doesn't necessarily disprove anything. There appear to be multiple causes of depression, and that's all that such a finding would support at this time (I thought this was understood by the general public as well, though the gist of the article seems to be that this is not so well known outside of scientific circles).

Subjectively it seems as if people are generally quick to draw the inference of chemical imbalance from depression symptoms. Not too surprising as the chemical imbalance hypothesis has actually been marketed in commercials broadcast nationwide; companies have a financial stake in people believing this hypothesis. But of course we can't really say in the absence of evidence to this effect.

 

[Poop-Loops]

This is a problem that is tough to overcome. Too many physicians have been trained to see depression as the disorder rather than as a symptom of another disorder and are quick to put patients on antidepressants and mask the real cause before fully investigating what else could be going on first.

Truth. I know people who in actuality had low testosterone or other hormone levels, or other problems that indirectly caused depression symptoms.

In my case, though, taking Prozac has helped immensely. I doubt it's placebo, because this lasted for a few months before tapering off.

Still, a good doctor will continue to monitor patients to see what changes. The doc I got my Prozac from has had depression for 20 years. He tried all sorts of things and keeps trying them. He told me of all the things he tried and I should try. He (and the therapist I went to) admitted that all this stuff is hard to understand, so they're simply going with the best thing they've got, but it's nowhere near guaranteed to work for everybody.

That's why there's more than 1 drug on the market, if you haven't noticed. Funny thing, the doc told me plain old fish oil has been shown to help with depression and told me to start taking it.

I'd say in this case Bad Science is putting the blame on the drug and not on the bad doctors. The drug works for a lot of people. It's up to the doctors to figure out who.

 

[Moonbear]

Truth. I know people who in actuality had low testosterone or other hormone levels, or other problems that indirectly caused depression symptoms.

In my case, though, taking Prozac has helped immensely. I doubt it's placebo, because this lasted for a few months before tapering off.

Still, a good doctor will continue to monitor patients to see what changes. The doc I got my Prozac from has had depression for 20 years. He tried all sorts of things and keeps trying them. He told me of all the things he tried and I should try. He (and the therapist I went to) admitted that all this stuff is hard to understand, so they're simply going with the best thing they've got, but it's nowhere near guaranteed to work for everybody.

That's why there's more than 1 drug on the market, if you haven't noticed. Funny thing, the doc told me plain old fish oil has been shown to help with depression and told me to start taking it.

I'd say in this case Bad Science is putting the blame on the drug and not on the bad doctors. The drug works for a lot of people. It's up to the doctors to figure out who.

It seems the important thing would be to rule out everything else first, then say, okay, it's not any of these other things, so it must be primary clinical depression. That doesn't mean it doesn't make sense to "bridge" treatment with an antidepressant, but it means one should consider other problems before deciding depression is the primary illness.

For example, I'd start with nutrition and exercise...if someone is eating poorly and not getting enough exercise, fix that first and see if they start feeling better. Endocrine problems are another obvious place to look, anything from low testosterone, as you pointed out, to diabetes or thyroid disorders or side effects of birth control pills could lead to these sorts of depressive symptoms. Or, high or low blood pressure could lead to such symptoms. As Ivan pointed out, allergies can lead to depressive symptoms, and the hardest ones to identify are the otherwise mild allergies where you aren't particularly bothered by things like sneezing and stuffiness, so don't realize the fatigue and lethargy are due to allergies. Other infections could also cause similar problems, such as Lyme disease. Or, just plain old sleep deprivation. With some, it's harder to tell than others, because it's unclear which is the symptom and which is the disorder, particularly with something like sleep disturbances and depression...it's a bit of a chicken and egg question.

 

[hypnagogue]

I'd say in this case Bad Science is putting the blame on the drug and not on the bad doctors. The drug works for a lot of people. It's up to the doctors to figure out who.

It's not about the efficacy of the drugs but rather the truth of the chemical imbalance hypothesis. If the hypothesis is false this doesn't preclude SSRIs from being effective.

 

[Poop-Loops]

Prozac has like 30 years of research into it. And they still don't fully understand what's going on, since there are plenty of non-responders. So yes, it could be something completely different doing the job.

 

[Chronos]

Doctors throw pills at the problem because diagnosis is expensive, uncertain and not routinely covered by insurance. Studies do, however, show that exercise is a very effective treatment for depression.

 

[jim mcnamara]

The HMO setup favors cookie cutter medicine. I had a colleague, a podiatrist. His take on it was that in order to make money, he must pass a patient through his office as fast as possible, and if you're lucky you can 'hand-off' a patient or write a one-time scrip for some pills. He has 80,000 patients assigned to his practice by the HMO. His practice is short on hand-offs and pill pushing, because he is usually on the receiving end of diabetic related secondary vascular disease outcomes on feet. Example, he has a tool that lops off toes. Uses it in the OR. Not the waiting room.

I think the 'one-time scrip' says it all in this case. When a physican is under pressure not to devote time to interact with a patient, the patient loses.