Oince the discovery in the late 1950's of imipramine (Tofranil®), the first tricyclic antidepressant (TCA), and iproniazid, the first monoamine oxidase inhibitor (MAOI), many other TCAs and MAOIs, now being considered the classical antidepressants, have become available. Their effectiveness has been shown in numerous studies, although according to nowadays standards well designed studies (placebo-controlled, defined diagnostic groups, the use of standardized rating scales) with these compounds are relatively scarce.
From the early 1980's the so called modern antidepressants have been introduced: the selective serotonin re-uptake inhibitors (SSRIs), the reversible selective monoamine oxidase-A inhibitors (RIMAs) and a variety of other compounds. All these drugs have been registered after their effectiveness had been shown in well designed, placebo-controlled studies. In defining the efficacy of antidepressants, registration authorities consider two aspects important: statistical evidence and clinical relevance.