Thanks for this Philip. Here are other flaws in the study to consider. The study authors state: “Second, the possibility that subtle adverse events that are recognized by the patient, but not of sufficient severity to be recorded, could influence the expectation of improvement, should not be excluded. However, the relatively low percentage of patients not reporting any early adverse events in most trials argues against side effects being under-reported.” Their conclusion is meaningless. It doesn’t matter what percentage of patients don’t report side effects because ALL of the patients in their first comparison group are in this category. As the authors correctly suggest, just because a patient does not report common side effects does not mean that they do not detect effects of the drug. If they detect effects of the drug, then the double blind is broken. So the part of their article that equated patients not reporting side effects with their not knowing they were receiving the drug has no validity because they did not address the question they claim to be addressing (Do patients receiving SSRI’s benefit from the placebo effect through detecting that they are receiving the active treatment?) The second conclusion, that side effect severity is not correlated with impact of any apparent benefit of the drug, also fails to actually address the researchers’ question. Note that the ratings were done by the psychiatrists (not the patients) so the psychiatrist being blind to whether or not the patient was receiving the drug is the crucial part of the double-blind. However, as soon as the patient reports a common side effect, then the blind is broken; the psychiatrist now knows the patient is receiving the drug. It doesn’t matter if the patient reports two or ten side effects or whether they are mild or severe. If you touch my toe I will know it, and touching it harder won’t make me know it any more. So suggesting that we should expect a stronger placebo effect if the reported side effects are stronger makes little sense. The double blind will be broken for both patient and psychiatrist with only one common mild side effect. The greatest travesty of this article, however, is not what it reports but what it cannot report. The question that the authors purport to answer is fairly easy to address. It would be simple for the FDA to conduct a double-blind study in which both patients and their psychiatrists are asked to “guess” whether the patient is receiving the drug or a placebo. Their confidence in this guess can also be assessed, and done repeatedly throughout the course of the study. If we had this data then WE wouldn’t have to guess about whether the double blind has been broken, or come up with the ridiculous post-hoc analyses that these authors did. In addition, within this same study two placebo groups can be used, one using an “inert” placebo like sugar, and the other an active placebo that has a noticeable effect on the body (e.g. caffeine). The active placebo is more likely to lead patients to believe that they have received the medication, so makes for a more fair and blind comparison. These ideas will not be new to people in the field. The fact that it would be easy to do, yet has not yet been done, while we continue to medicate many millions of people with potentially fatal consequences; that is a travesty.