Background. The number of antidepressant drugs
available in the market has grown rapidly in the
last few years. The present paper underlines some of the pre-clinical
and clinical problems that call
close attention from the regulatory authorities when approving new drugs.
Methods. We present here a review of the literature.
Results. A wide heterogeneity in the action of the various
antidepressants precludes any single
theory about the pathogenesis and therapy of depression. Antidepressant
activity, in fact, may be
achieved by acting on a number of different monoaminergic mechanisms. The
variety in the
neurochemical effects of antidepressants is not reflected in clinical
trials, which tend to stereotypy.
In many cases clinical trials aim at demonstrating equivalence rather
than differences in efficacy.
Regulatory authorities should, therefore, pay attention in accepting
the equivalence of effects of a
new drug in relation to a reference one: most clinical trials of new
antidepressant drugs do not have
the power to detect clinically relevant differences.
Conclusions. Unconventional new pre-clinical tests are
needed to generate antidepressants with a
different mechanism of action. Clinical studies are needed to promote objective
evaluation of the cost, benefits and toxic effects of new antidepressants.