1 Boring Old Man

Antidepressants and the Sound of One Hand Clapping
Psychiatric Times
By Ronald W. Pies, MD
October 10, 2011

^{Two hands clap and there is a sound. What is the sound of one hand?}

^{—Hakuin Ekaku [Rinzai Zen Master, 1686-1768]}

^{… Nearly all acute efficacy studies of ADs make use of the HAM-D, which is actually subject to a variety of confounds, such as the training of the HAM-D raters. And, depending on whether one considers a mean change of 2 or 3 points on the HAM-D to be clinically significant, meta-analyses of acute AD efficacy studies lead to different conclusions. Furthermore, placebo responses have been rising in recent years because of a variety of factors, such as multisite studies and use of less severely depressed patients. It is hard to apply the results of randomized, placebo-controlled studies to clinical practice. Thus, in a superb review, Prof Hans-Jürgen Möller concludes:}

^{“In interpreting such mean [HAM-D] score differences, it has to be stated that the mean of the pre-post differences of the placebo groups and the verum [active medication] groups only give a global estimation of efficacy under the artificial conditions of placebo-controlled trials, in which, due to the principal characteristics of the design, the verum response is underestimated and the placebo response is overvalued… One cannot conclude very much from this for everyday clinical practice, especially not on the efficacy for special patient subgroups or even for individual patients.”}

^{Furthermore, as an extensive critique of the much-discussed Kirsch meta-analysis pointed out,}

^{“Perhaps the most overlooked aspect of the data included in Kirsch et al. [2008] is that it is not about the effects of antidepressants upon depression, but rather about the effects of antidepressants on the HAMD … [and the HAM-D] describes a construct of depression which corresponds poorly to that found in DSM-IV…}

^{Having recently reviewed the extensive antidepressant literature for a paper in press, my own conclusion is that ADs show, overall, modest-to-moderate efficacy compared with the placebo condition in acute treatment studies — depending on the type and severity of depression… The most robust AD effects in acute treatment studies seem to emerge in more severely depressed patients … and among those with melancholic features. However, a recent re-analysis of the Kirsch data by Ghaemi and Vöhringer found acute antidepressant efficacy in both moderate and severe — but not in mild — major depression. This should not really surprise us. All other factors being equal, the farther we move down the continuum from severe melancholic major depression toward normal sadness, the less pronounced the difference between specific and nonspecific interventions…}

^…

^{And so, overall, what is my verdict on antidepressants? In my estimation, our present medications for depression are only mediocre. For moderate to severe, and especially melancholic, cases of major depression, ADs are effective and sometimes lifesaving, particularly when part of a comprehensive treatment plan that includes psychotherapy. And, there is convincing evidence that ADs prevent relapse at least during the 6 months or so after a bout of major depression. For mild, non-melancholic cases of depression, I generally favor beginning with psychotherapy, given the “costs” of antidepressant side effects. In this regard, we urgently need to find antidepressants that are more effective and better tolerated… In sum: I do not hear loud applause for our current antidepressant armamentarium. I believe I hear the sound of one hand clapping…}