The DUAG studies showed that in well-designed and rigorously executed multisite drug trials three representatives (citalopram, paroxetine, and moclobemide) from two classes of recent antidepressant drugs were less effective than the standard reference drug, clomipramine. The most important reasons for the superiority of clomipramine was probably that clomipramine was given in a high and fixed dose of 150 mg per day throughout the entire treatment period and that patient compliance was ensured through drug monitoring. When the DUAG studies are compared with "no difference" studies, the difference between DUAG and others lies not so much in a different efficacy of the test drugs but in the efficacy of the reference drugs, where clomipramine in the DUAG studies was more effective than reference tricyclics in most other studies with flexible dose regimens. A relatively high rate of adverse drug reactions with clomipramine administered in high and fixed doses was probably due to a considerable interindividual variability in the pharmacokinetic properties. (Gram 1990), and the development of side effects may be predicted and prevented when better knowledge of plasma concentration and dose-response relations for classical tricyclic antidepressants allow individual dose adjustments. Such studies are under way with in the DUAG. The results of such studies may reduce the need for new antidepressants which, although less toxic than the classical tricyclics, may prove to be also less potent. The DUAG studies were performed in hospitalized, moderately to severely, endogeneously depressed adult patients and conclusions from the DUAG studies about the superiority of clomipramine over three recent antidepressants cannot readily be generalized to cover less homogeneous groups of outpatients with milder depression.(ABSTRACT TRUNCATED AT 250 WORDS)