[LINK] Antidepressants: Bad Drugs… Or Bad Patients?
Illuminating post on Neuroskeptic:
Some Quotes:
Why is it that modern trials of antidepressant drugs increasingly show no benefit of the drugs over placebo?.....
They suggest that maybe it’s the patients fault: Participation that is induced by cash payments may lead subjects to exaggerate their symptoms [i.e. in order to get included into the trial]… Another contributing factor to high placebo response rates may be the extent to which the volunteers in antidepressant trials are really generalizable to patients in clinical practice.
Since the initial antidepressant trials in the 1960s, participants have gone from being patients who were recruited primarily from inpatient psychiatric populations to outpatient volunteers who are often recruited by advertisements. At times, these symptomatic volunteers have participated in other trials. When we contact potential participants to schedule screening, they often ask to be reminded which trial we are screening for or mistake our research trial for a different protocol in which they recently participated.
A few years ago I was running a study recruiting people who’d recovered from psychiatric illness. The main source of volunteers was online adverts..… We recruited about 20 people. No fewer than 3 turned out to have enrolled in other studies and lied about it. After I realized this I Googled the offender’s names and two of them turned up in the court pages of the local newspaper pleading guilty to various petty crimes.
In my view, the authors miss out on the real problem with recruiting depressed people through adverts: depressed people don’t tend to respond to adverts, because depressed people don’t do anything. That’s why they call it depression.
So while you wouldn’t go looking for aquaphobic people in a swimming pool, I’m not sure we should be looking for depressed people through adverts.
Could similar mechanisms hold true for other drugs?
Not exactly. Depression includes both misery and inertia, and they’re somewhat independent from each other. There are people who get a good bit done, but are miserable—sometimes suicidal—for no apparent reason. There are people who can enjoy low-effort hobbies, but have a very hard time doing much of anything else.
I can see that being an issue for subjective side-effect reporting (e.g. headache, nausea), but not for objectively measurable data, such as blood cholesterol levels, survival rates, etc. There you may have the “true” placebo effect, but probably not the described selection effects.
If you want to be included in a study, it is fairly easy to adjust to give yourself some symptoms. I used to eat eggs every morning. When I stopped—boom − 50 point drop in cholesterol. It won’t work for everything, but diet and pharmaceuticals could give you a whole lot of physical symptoms if you were so inclined. Disease symptoms can be cured. Probably at least as easy to induce them. There are lots of ways people sell their bodies for money. Inducing temporary disease symptoms surely isn’t the worst.
This is especially true for antidepressants because some are only effective on more severe cases (eg Zoloft); self-selection will yield a body of faux-depressed and mildly depressed people on whom the drug has no result.
EDIT: Apparently I was thinking of a different drug.
Zoloft has actually been found to be one of the better drugs for cases of mild chronic depression (“dysthymia”).
This is especially true for antidepressants because some are only effective on more severe cases (eg Zoloft); self-selection will yield a body of faux-depressed and mildly depressed people on whom the drug has no result.
Hmm. This issue could actually be quite broad, and taint a lot of pharmaceutical research data pretty badly. How many people do you suppose there are, who go around signing up for every paid trial they can find? They’d have to defraud the researchers, of course; no one would allow a patient like that into their study knowingly. And what do you suppose that sort of person would do, and how would it be reflected in the data?
Well, if you were defrauding researchers to get them to pay you for participating in their studies, you wouldn’t actually take the drugs when they weren’t looking. Normal risk from a drug trial turns into a major risk when you’re in a bunch of trials at once with possible interactions. But you wouldn’t want to make that obvious, because then you might get caught. So you’d start by figuring out whether you were in the placebo group or not, either by trying the pills once and seeing if there was an effect, or breaking them open and seeing if they taste like sugar, or something like that. If in the placebo group, you’d answer all questions consistently with getting no effect. If in the experimental group, you’d try to match the experimenters’ expectations, to avoid attention; which would mean making up generic side effects, and claiming some benefit.
Now, how many fraudsters like that would it take, to ruin a study? Since studies count as successful with small effect sizes, a small percentage will do. Now, how many fraudsters are actually in studies, and do they act like I just described?
I propose a “study on study fraud”. It’s advertised as an antidepressant study, is conducted like one, and pays well. However, all subjects get sugar pills, in a special bottle that looks normal but which contains electronics that log every time it’s opened, and which weighs its contents when it’s closed. Anyone who empties the bottle all at once is a fraudster. This would yield a measurement of the fraud rate, a list of names to strike from other studies and re-analyze the data, and some survey and interviews which show what fraudsters’ responses look like.