Although there is no doubt about its efficiency, pharmacotherapy of depression still faces several problems that have to be focused upon and hopefully solved. Besides the problem of drug-resistance and delayed response, the need to achieve remission has become increasingly important.

As for the near future, there is great hope that new mechanisms of action can overcome the limitations of the traditional and current antidepressant medications. Unfortunately, some of the recent developments that raised the most interest either turned out to be less effective than hoped, such as the substance P antagonists, or did not yet lead to a drug likely to be marketed in the near future, such as CRF antagonists, for example. On the other hand the first melatonergic antidepressant, agomelatine, is seen as a successful new development.

Drug development can currently be based on improved brain imaging techniques, better animal models, and an increased knowledge of genetic markers. Hopefully this will result in a change in the pharmacotherapy of depression and psychiatric diseases in general. From a clinical point of view, new antidepressants should target the following unmet needs: early onset of action; increased proportion of remission; broad spectrum of efficacy including physical symptoms, pain, sleep disorders, circadian rhythm disorders, etc; good efficacy in subtypes of depression, such as atypical depression; efficacy in bipolar depression without inducing switches to mania; lack of side effects of TCAs and modern antidepressants, especially lack of cardiac side effects, anticholinergic side effects, sedation, weight gain, sexual side effects, etc.