THE NEWER ANTIDEPRESSANT drugs have now been used experimentally and clinically for approximately seven years. Their place in the physician's armamentarium is still far from clear, although many clinicians feel that the drugs are useful and effective. However, controlled clinical trials of these agents have not always led to unequivocally positive findings. Even when such findings have been favorable to the drug under study, the differences between the efficacy of the drug and a placebo have not been as great as one might wish, or as one might have anticipated after reading published reports of uncontrolled studies. Probably two major factors combine to produce this discrepancy. First, depression is, on the whole, one of the psychiatric conditions with the best prognosis for eventual recovery with or without treatment. Most depressions are self-limited and the spontaneous or placebo-induced improvement rate is often high. For example, in a series of nine controlled