Predictors of placebo response in a randomized, controlled trial of phytotherapy in menopause.

Objective: The aim of this study was to evaluate predictors of the placebo response in a randomized, placebo-controlled, double-blind trial of a phytotherapeutic combination for the treatment of menopausal symptoms.

Methods: A post hoc analysis was conducted on data from 46 placebo participants completing the study. Variables at baseline were investigated for prediction of improvement on any of the endpoints of flushing, depression measured on the Hamilton Depression Inventory, and menopausal symptoms measured on the Greene Climacteric Scale. Hierarchical linear regression analyses were carried out on the individual endpoints, controlling for baseline scores. Multivariate linear regression analysis was also conducted on these three endpoints in combination.

Results: Higher anxiety at study entry predicted placebo response on all three outcome measures individually (flushing: R = 0.33, P = 0.03; depression: R = 0.34, P < 0.001; and Greene Climacteric score: R = 0.24, P = 0.04); and in combination (P = 0.002), as did total Greene Climacteric scores at study entry (R = 0.24, P = 0.005). Improvement during nontreatment run-in predicted placebo response for depression (P = 0.005), menopausal symptoms (R = 0.28, P = 0.013), and the three combined endpoints (P = 0.015). Severity of scores at baseline predicted subsequent improvement on the Greene Climacteric scores only (r = 0.038, P = 0.009).

Conclusions: These findings may facilitate identification of potential placebo responders in future randomized controlled trials on menopausal symptoms and have relevance to study design in this context. Further research is required.