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News - Active placebos versus antidepressants

clinical trials

The breaking of blind by patients in clinical trials may be the key to understanding why all types of different drugs in our metaanalysis, even those that were not antidepressants, had the same effect on depression. When patients are kept blind, they do not know whether they have been given the drug or the placebo. Hence, their expectation of getting better is tempered by their knowledge that they might have been given a placebo.

But when they break blind, their expectations change. If they know they have been given the active drug, rather than the placebo, they become much more confident of improving. Conversely, if they realize that they are in the placebo group, their expectancy of improvement declines. Expectations of improvement are a central factor in the placebo effect. People expect to get better when given a treatment, and in many conditions that expectation can produce the improvement they expect as a sort of selffulfilling prophecy. In other words, patients who break blind in clinical trials might improve more on the active drug than on the placebo, simply because they know they are getting a real drug rather than a sugar pill. If they believe they are on the active drug, they have a greater expectation of improvement, and because of these enhanced expectations they actually do improve more. On the other hand, if they realize they have been given a placebo, they expect – and therefore experience – less improvement.

This is not just speculation. It is backed by evidence. Some antidepressant trials are conducted without placebo groups.

These are called comparator trials, because they compare one antidepressant to another. In comparator trials, all patients are given an active drug, and they know that there is no chance at all of getting a placebo. A group of researchers led by Joel Sneed at Columbia University in New York compared the response of
patients in comparator trials to that of patients in placebocontrolled trials. The researchers found that patients in the comparator trials were significantly more likely to improve. Specifically, 60 per cent of patients responded to antidepressants in the comparator trials, but only 46 per cent were rated as improved in the placebo-controlled trials. 

This difference resulted from patients knowing that they were definitely getting an active drug versus knowing that they might be getting a placebo, as that was the only difference between the two types of trials that were compared. Because it was produced by what the patients believed about the drug, rather than by the drug itself, it can be considered a placebo effect.


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