Addressing risk of bias in trials of cognitive behavioral therapy.

A recent network meta-analysis by Zhu and colleagues reported in the Shanghai Archives of Psychiatry compared two different comparators (psychological placebo and waitlist control) in trials assessing the effectiveness of cognitive behavioral therapy (CBT) for the treatment of generalized anxiety disorder (GAD). CBT was superior to both of these control conditions, but psychological placebo was superior to waitlist. However, we argue that the term 'psychological placebo' is a misnomer because the impossibility of effectively blinding participants to treatment allocation in CBT trials makes it impossible to control for placebo effects. This failure to blind participants and therapists - and the resultant high risk of bias - was the main reason Zhu and colleagues found that the overall quality of the evidence supporting the conclusion that CBT is effective for GAD is poor. This is a general problem in all psychotherapy trials, which suffer from well-documented methodological and conceptual problems that prevent adequate placebo control and undermine casual inference. We discuss these problems and suggest potential solutions. We conclude that, while it may be difficult to remove potential bias in randomized controlled trials of psychotherapy, we can improve on the status quo by integrating basic science within applied trials to adjust for these biases and, thus, improve the strength of the causal inferences.