Active Placebo Studies show smaller benefits from Antidepressants

In most of the better clinical studies, a "placebo group" acts as a control. The placebo would consist of something totally inert, such as a capsule with nothing inside, or possibly with a small quantity of a sugar such as lactose.

The idea of an "active placebo" is interesting: in this case, the placebo is an agent shown not to have any beneficial or detrimental effect on the disease in question, but which clearly has side-effects.

An example would be using a tablet of Gravol (dimenhydrinate) as the "placebo". It is not an antidepressant, but it has side-effects (sedation, dry mouth, etc.). In this way, it is a more convincing placebo, since a person taking an agent which produces side effects is more likely to believe that they are taking the "active" agent. If a person is taking a placebo they strongly believe to be a placebo (since it produces no side effects) they are less likely to have any "placebo effect" response, and the whole point of the placebo control will be relatively "unblinded."

There is a body of research literature looking at using "active placebo" vs. antidepressants to treat depression.

http://www.ncbi.nlm.nih.gov/pubmed/9614471

{a 1998 meta-analysis from the British Journal of Psychiatry showing that the effect sizes of antidepressant therapy are only about half as large when compared against an active placebo, rather than an inert placebo}

http://www.ncbi.nlm.nih.gov/pubmed/14974002
{a 2004 Cochrane review with similar findings}

These results support the evidence that antidepressants work -- but they suggest that probably most of the studies overestimate how well they work, because they are measured against inert placebos in most cases.

I think that more clinical studies need to include active placebos.

I post this not to be cynical, or to discourage the use of antidepressants--as you can see from the rest of this blog, I strongly support medication trials to treat psychiatric problems--but I believe that we have to always search for the most accurate, least biased sources of information. We need to be wary of exaggerated claims about the effectiveness of anything, especially since I see in my practice that many of the treatments don't seem to work quite as well as the ads claim they should.