Algo más que monoaminas en el tratamiento de la depresiónmecanismos neurobiológicos emergentes de los antidepresivos del siglo XXI

  1. Cecilio Álamo González 1
  2. Francisco López-Muñoz 2
  3. Cristina Zaragozá 1
  1. 1 Universidad de Alcalá

    Universidad de Alcalá

    Alcalá de Henares, España


  2. 2 Universidad Camilo José Cela

    Universidad Camilo José Cela

    Villanueva de la Cañada, España


RIECS: Revista de Investigación y Educación en Ciencias de la Salud

ISSN: 2530-2787

Year of publication: 2020

Volume: 5

Issue: 2

Pages: 49-80

Type: Article

DOI: 10.37536/RIECS.2020.5.2.214 DIALNET GOOGLE SCHOLAR lock_opene_Buah editor

More publications in: RIECS: Revista de Investigación y Educación en Ciencias de la Salud


Classically, the pharmacological treatment of depression has been carried out with monoaminergic antidepressants, which present a series of limitations, such as a slow onset of action, an inadequate antidepressant response, sexual dysfunction or a tolerability that can be improved. In this review we will analyze new pathophysiological mechanisms involved in depression as targets for the search for different antidepressants. In the field of endocrinology, the results are disappointing, ephemeral (TRH), limited (thyroid hormones), doubtful (CRH1 antagonists), controversial (estrogens) or not very effective (androgens). Several neuropeptides are implicated in the pathogenesis of depression, such as antidiuretic hormone, oxytocin, substance P, neuropeptide Y or galanin, but their therapeutic approach has not yielded therapeutic results. The relationship between depression and inflammatory processes is clear, but the efficacy data, often anecdotal, of some anti-inflammatory drugs, TNF antagonists or monoclonal antibodies cannot be generalized. The participation of the endogenous opioid system has also been explored, but its addictive potential means that we do not currently have "antidepressant opioids". The glutamatergic hypothesis of depression has been working for more than 3 decades and finally seems to have given results: esketamine, an isomer of ketamine, has shown, thanks to a robust clinical development program, that it is an fast-acting antidepressant, effective in resistant depression, with an acceptable tolerability, which has motivated its authorization in resistant depression in association with conventional antidepressants. Esketamine is the therapeutic answer to the "glutamatergic hypothesis of depression".