Beyond monoamines towards the development of novel antidepressants

Oltre le monoamine al fine di sviluppare nuovi farmaci antidepressivi

M. Fornaro1,2

1 Department of “Scienze della Formazione”, University of Catania, Italy; 2 Department of Psychiatry, Veteran Affairs (VA) Hospital, University of California (UCSD), La Hoya, San Diego, CA, USA


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.


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.


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.

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