LAUSR

289 of spontaneous remission, about half was due to nonspecific factors that would occur in any given treatment, and only about a sixth was due to the specific effects of presumably “active” treatments. Because all of the studies that he included in his meta-analysis were randomized controlled trials, he could legitimately draw a causal inference with respect to the nonspecific factors. After decades of process research that sought to determine how treatments work, but could not answer the question as to whether they actually do work (have a causal effect), Cuijpers has provided a most compelling answer and a very clever roadmap for others to follow. I do think, however, that it is premature for Cuijpers to conclude that there is no evidence that CBT works through cognitive change to produce change in depression. As he points out, the problem is that it is easier to detect an effect than it is to explain it, largely because we can use powerful experimental methods to test for causal effects of treatment on both the purported mediator and the outcome, but are left to rely on purely correlational methods to try to draw a causal inference regarding the link between me diator and outcome. That being said, I think he is wrong when he asserts that the absence of specificity denotes an absence of causal effect. If cognition did not change over the course of CBT then it could not be a mediator, but the fact that it shows comparable change in ADM does not rule such a causal process out. The problem is that a given process can be both a cause and a consequence of change. In an earlier trial we found that change in depression-relevant cognition predicted subsequent change in depressive symptoms with CBT but not with ADM, which likely worked through other causal mechanisms. The issue is one of moderated mediation in which the treatment affects the nature of the relation between the purported mech anisms and the outcome. While CBT produces change in cognition that leads to (mediated) subsequent change in depression, ADM produces change in depression through other mechanisms that lead to subsequent change in cognition. Absolute change in cognition was comparable between the two treatment modalities, but the causal paths that led to that change were likely quite distinct. Whereas moderated mediation as a consequence of differential treatment tends to obscure mediational effects that might be present, because it alters the apparent relation between the mediator and the outcome, moderated mediation as a function of individual differences among patients can be used to amplify that signal. As Kazdin first pointed out, any instance of moderation suggests that different causal mechanisms may be at work in different patients. This means that tests of mediation can be made more precise (and therefore more powerful) if we include patient by treatment interactions in those analyses. I agree with Cuijpers that mediation is difficult to detect, but a more sophisticated approach that takes moderated mediation into account may help to clarify the process.