Beyond monoamines towards the development of novel antidepressants

Objective: Herein, a concise review is presented on the current and most promising antidepressant pharmacological agents for management of depression. Materials and methods: A PubMed search (1966 - February 2012) was performed using the following keywords or their combination: "depression"; "major depressive disorder": "antidepressants"; "novel antidepressant targets"; "monoamine"; "novel antidepressants". Additional literature sources, including most authoritative and updated edited books or pamphlets were examined accordingly. Results: All relevant literature sources written in English were evaluated giving priority to RCTs and meta-analyses. At present, the pharmacological management of depression appears is characterized by a wide variety of different augmentation or switching approaches (Fig. 1). Nonetheless, response rates remain substantially unsatisfactory, thus prompting for the development of novel agents with different mechanisms of action. Conclusions: Shifting the interest for novel antidepressant drugs beyond the monoaminergic modulation represents (Tables I-III) an intriguing opportunity to enhance response rates of depression, although other issues, including revision of current nosological boundaries, should also be considered.