Revised: October 21, 2011
Accepted: December 20, 2011
Published online: February 9, 2012
The basic consideration in the field of antidepressants is that tests to model depression do not exist, as depression etiopathology is unknown. So far, any kind of proposed model for depression needs to satisfy construct, face and predictive validities. In the present editorial, this idea is challenged, based on the fact that “old” methods can only reveal therapeutical “me-too” drugs and that there is no longer a need of therapeutical “me-too” drugs in the field of antidepressants. Since reduction in the number of antidepressant non-responders is a real medical need, the predictive validity of animal models will be challenged in the future, as the new methods should be based on antidepressant-insensitive animals. Moreover, antidepressants exert similar effects in depressed and non-depressed subjects, but mood normalization is only induced in depressed patients. This implies that the use of normal cells and animals only involves pharmacological rather than therapeutical actions of drugs. Therefore, the use of environmental-induced changes, in the hope that these can evidence antidepressant-insensitive animals, will predominantly be used in the future. In the choice of experimental settings, other factors need to be taken into consideration: (1) gender of animals, as depression affects females more than males, (2) natural rhythmicity in drug effects; (3) pharmacokinetics; and (4) possible biomarker(s) to be measured. There are no golden recipes to discover new antidepressants but the experimental long-term strategy should very clearly be declared before starting the experiments.