R.P. Greenberg, S. Fisher, Examining antidepressant effectiveness: findings, ambiguities and some vexing puzzles, in R.P. Greenberg and S. Fisher (eds), The Limits of Biological Treatments for Psychological Distress - Comparisons with Psychotherapy and Placebo, [Hillsdale, New Jersey: Lawrence Erlbaum Associates, 1989], 1-37.

CM writes: I wish I'd come across this important, high protein review before publication of ADWEB, though it does not specifically touch on SSRIs. It is nevertheless, thoroughly relevant to the question "Do antidepressants work?" for what it says about the limitations of trials' design and their effect on reported outcomes. It  includes especially good reviews of antidepressant versus active placebo studies, and of the significance of newer versus older trial investigations. One of several excellent chapters between the two same covers, this paper concludes as follows:

"Overall, we would underscore that the purpose of our critique is to raise questions about the magnitude of the therapeutic efficacy of the antidepressants and also the scientific methodology employed to test that efficacy. It is important to emphasize that we are not suggesting that antidepressants are simply dramatic placebos. It may well be that the action of, for example, the tricyclics at specific brain sites significantly decreases depressive symptomatology. However, until adequate studies involving active placebos are carried out, it is difficult to disentangle the direct physiological variance from that due to placebo amplification. Depressed patients who detect improvement in their state, upon receiving an antidepressant may perceive this as a dramatic signal that there is hope of recovery. Such an expectation plus the vivid body experiences that are usually initiated by antidepressants plus the perceived positive therapeutic expectation of those administering the treatment may well synergistically result in considerable clinical improvement. Overall, it is difficult to see how a fair therapeutic evaluation can be attained unless an active placebo is included in experimental designs. If one generalizes, this would apply also to the evaluation of any drug directed at symptoms with a large psychological component".

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