St John's Wort and Depression

To the Editor: Dr Davidson and colleagues¹ found that sertraline, hypericum (St John's wort), and placebo had similar efficacy for treatment of depression. I agree with Kupfer and Frank,² who stated in their Editorial that the trial had low assay sensitivity. This does not simply mean low power for the primary outcome, however. It also indicates that the process and outcome of the study itself could not answer the postulated question, which is likely due to multiple small factors that enhance what Moerman and I have called the meaning or healing response.³ For example, because sertraline produced more physiological effects than placebo or hypericum, subjects were not completely blinded to treatment assignment. When physiological effects of treatment are experienced by some patients receiving an active treatment in depression studies, effect sizes are falsely elevated unless an active placebo that mimics these effects is used.⁴ Such an active placebo was not used in this study.