OBJECTIVES: To compare the sensitivity to change of the Hamilton Depression Rating Scale (HAMD) and the Montgomery-Åsberg Depression Rating Scale (MADRS) as outcome measures in antidepressant randomised controlled trials (RCTs). METHODS: Data come from 2 RCTs (studies A and B) which assessed the efficacy of SSRIs plus pindolol or plus placebo in patients with Major Depression (MD). Study B recruited treatment resistant patients. Both studies included the HAMD and the MADRS as outcome measures. Study A did 10 follow-up measurements (since day 0 to day 42). Study B did 3 follow-up measurements (since day 0 to day 10). Standardised estimates for the change in the severity of depression since day 0 were calculated by a within-group effect size (dw) which accounted for the correlation between measurement times. RESULTS: Study A showed a decreasing curvilinear pattern for the HAMD effect sizes (0, -0.55, -0.96, -1.25, -1.53, -1.97, -2.27, -2.15, -2.41, -2.57) which overlapped perfectly with the MADRS estimates (0, -0.56, -0.95, -1.23, -1.56, -1.88, -2.13, -2.17, -2.45, -2.64). Similar pattern was obtained in study B (HAMD: 0, -0.32, -0.62; MADRS: 0, -0.22, -0.52). Additionally, our estimates point to a reliable decrease of the severity of depression even since the first post-baseline measurement (study A, HAMD dw = -0.55 [95% CI = -0.73 to -0.37], MADRS dw = -0.56 [95% CI = -0.74 to -0.38]; study B, HAMD dw = -0.32 [95% CI = -0.52 to -0.11], MADRS dw = -0.22 [95% CI = -0.39 to -0.05]). CONCLUSION: Contrary to common beliefs, the HAMD shows an indistinguishable pattern of change from the one obtained with the MADRS, either in common MD populations (study A), or in treatment resistant patients (study B). Also, reliable symptomatic changes seem to appear early on in the course of an antidepressant treatment.