Moclobemide: a paradigm of research in clinical psychopharmacology

The pre-clinical development of moclobemide is an example of broad research combined with serendipity. Moclobemide was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and moclobemide was then suspected of being an antipsychotic before its specific and reversible monoamine oxidase (MAO)-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977. In the first stage, multiple, small open and double-blind studies were carried out. Two decisive, large, multicentre, double-blind studies were later performed in Latin America and Austria. Further trials have confirmed the broad antidepressant activity of reversible monoamine oxidase inhibitors (RIMA), which is not confined to any one subtype of depression and which show good tolerability and low toxicity. Since moclobemide has been available on the market, extensive meta-analyses of a large data set provided a series of methodological results: factor structure of the Hamilton Depression Scale (HAMD), optimal criteria of efficacy, predictors of response, onset of action for antidepressants and placebo.