Why is it that modern trials of antidepressant drugs increasingly showno benefit of the drugs over placebo? This is the question asked by Cornell psychiatrists Brody et al in an American Journal of Psychiatry opinion piece.
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.
They then recount the tale of two "professional subjects" who claimed to be depressed and enrolled in two antidepressant trials simultaneously, without telling the researchers; it only came to light when someone involved in both studies spotted the duplicate names.
I've been the victim of such nonsense myself, as have many of colleagues - it's a perennial watercooler topic. 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.
That study was a learning experience. What I learned is that House was right. 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.
Another volunteer was left handed and, upon realizing that I was only recruiting right-handed people, discretely switched his pen to his right hand and then took 5 minutes trying to fill out a form with his off hand. He didn't make it in, but if I hadn't been paying attention he would have.
So yes, it is a problem. However, it would have to be taking place on a massive scale for it to be having a significant effect on antidepressant trial results and this really seems pretty unlikely.
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.
Getting recruited into a modern clinical trial is actually quite a challenge. There are many pieces of paper to fill in, calls to return, appointments to attend. Turn up late to the screening visit, or otherwise make life difficult for the study staff, and you'll be marked down as "unreliable" and they'll find someone who plays by the rules. Modern trials are very expensive. The last thing a study sponsor wants is a volunteer who will end up forgetting to take their pills on time.
Depression, unfortunately, makes you bad at doing things. You procrastinate, you forget, you put things off until too late, you have a change of heart and decide not to, you get cold feet, you can't be bothered... That goes for things as simple as cooking dinner in severe cases, let alone something as complicated as taking part in a trial.
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.
Brody B, Leon AC, and Kocsis JH (2011). Antidepressant clinical trials and subject recruitment: just who are symptomatic volunteers? The American journal of psychiatry, 168 (12), 1245-7 PMID: 22193668
