Thursday, January 05, 2006

Got Placebo?

It was just over 3 years ago, and reporters breathlessly heralded the news: "St. John's Wort Is Ineffective For Depression". Unfortunately, they got the story wrong, and missed the real story sitting right under their noses.

Here's what happened. The National Institutes of Health had just sponsored a large outcome study in which hundreds of depressed patients were randomly assigned to one of three treatment conditions: Zoloft (the best-selling antidepressant), St. John's Wort, or Placebo (an inert sugar pill). None of the treatments worked particularly well. After 8 weeks, the following proportions of patients were found to be recovered within each treatment group:

Placebo - 32%
Zoloft - 25%
St. John's Wort - 24%

Notice anything interesting? Yes, oddly enough, the sugar pill yielded the best results of all.(Statistically speaking, though, the 3 treatments were judged to be in a virtual tie.) Now, in order for medical researchers to conclude that any given drug is effective, it has to outperform a placebo control condition. Clearly, this didn't happen for St. John's Wort (hence the headlines) . . . but it didn't happen for Zoloft either (a fact that was completely ignored by the press)!

However, at this point, perhaps you're thinking, "Surely this study is some sort of anomaly. A fluke outcome. We already know that Zoloft and similar drugs are much more effective than a sugar pill." But do we?

Clinical researcher Irving Kirsch and his colleagues recently petitioned the Food and Drug Administration under the Freedom of Information Act for data on the 47 drug trials submitted by the pharmaceutical industry in their quest to get FDA approval for 6 of the most popular antidepressant medications (Prozac, Paxil, Zoloft, Celexa, Effexor, and Serzone). Most of these drug studies had never even been published, as drug companies tend only to publish the studies that show their drugs in a favorable light . . . but the FDA keeps permanent records of every such trial.

What did the FDA records show? Remarkably, Kirsch and colleagues found that in the majority of these drug trials, the antidepressant did not beat the placebo. In fact, when the researchers averaged across all 47 studies, they found that the placebo led to symptom reduction that was fully 85% as large as that of the active medications. This amounted to a 2-point average difference on a 52-point symptom rating scale; this magnitude of difference is not considered to be clinically significant.

Does this mean that Zoloft and similar drugs don't work? No. It's clear that they lead to complete remission for about 1/3 of the patients who take them (and to some improvement for many others) . . . It's just that much of this benefit for many patients is based on the placebo effect. The data on this point are crystal clear.

And how does the placebo effect work? This will be the subject of an upcoming post . . .

7 comments:

Dr. Deborah Serani said...

The Power of the Placebo effect never ceases to amaze me...

Looking forward to your next post. I linked you on my blog.

Have a great weekend,
Deb

Heidi said...

I saw your reply on Dr. Deb's blog and this entry caught my attention.

Years ago I was involved in a clinical study for anxiety/depression with Zolot.

The particpants were told some will get the " medication" and some " placebo". My gut instincts are very strong and I just knew that I ended up with the Placebo.. Why ..because the pill was sweet!

I was really upset but wanted to be 100% sure because the DR's don't know themselves as we were told.

I went to a nearby drugstore..Told the pharmacist the situation and if I can just " taste" 1 zoloft pill. I was determined and convincing because he ended up giving me one..I was actually shocked he did but I was right..The medication was bitter as I knew it would be.

I called the Dr. who was in charge of the Study and dropped out.

My question is..Is there such a thing as a " bitter" tasting placebo pill?

Psych Pundit said...

Deb - Thanks so much for the link! I'll do my best to return the favor this week . . .

Heidi - I appreciate hearing about your experience with placebo. Typically, when researchers ask patients whether they think they're getting placebo or active medication, about 75% of patients on placebo think they're getting the active drug! However, in some cases (like yours) the investigators don't do a very good job of ensuring that the placebo looks, feels, and tastes exactly like the drug (it's supposed to). My guess is that the taste-free coating on your placebo pill was too thin, such that it quickly dissolved and allowed you to taste the sugar (that shouldn't happen). Make sense?

Heidi said...

It makes perfect sense...Thankyou :)

Blair said...

Good post.. Keep it up...

L K Tucker said...

Both the study and the investigation that followed assumed that the pill taken, real or placebo, was the only active agent during the testing.

I have searched for five years and cannot find any study that controls for Subliminal Distraction.

SD was discovered when it caused mental breaks for office workers. The cubicle solved that problem but it is so simple that the circumstances for exposure can be created almost anywhere.

If exposure decreases symptoms decrease. An increase would cause a responding increase in symptoms.

It would take only one or two subjects with this exposure to change study results.

VisionAndPsychosis.Net is the only source of information about this phenomenon on the Internet.

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