Abstract
Since the introduction of antidepressants to psychopharmacology in the 1960s, the Hamilton Depression Rating Scale (HAM-D) has been the most frequently used rating scale for depression. When used as a scale for prediction of outcome with antidepressants, the HAM-D, by its total score, has obtained limited use analogous to the Diagnostic and Statistical Manual of Mental Disorders. 4th ed (DSM-IV) diagnosis of major depression. Most research has been devoted to the use of the HAM-D to discriminate between placebo and active drugs or to show dose-response relationship in patients with major depression. An improvement in the total HAM-D score during a drug trial does not, however, in itself qualify the drug as an antidepressant, because the total score is not a sufficient statistic. The problem of statistical versus clinical significance when analyzing placebo-controlled trials, including dose-response relationship, is outlined, with the recommendation to use effect size statistics.