Algo más que monoaminas en el tratamiento de la depresión: Mecanismos neurobiológicos emergentes de los antidepresivos del siglo XXI
DOI:
https://doi.org/10.37536/RIECS.2020.5.2.214Keywords:
Alopregnanolona, Antidepresivos, Depresión, Hipótesis glutamatérgica, Ketamina, Esketamina, RiluzolAbstract
Clásicamente, el tratamiento farmacológico de la depresión se ha realizado con antidepresivos monoaminérgicos, que presentan una serie de limitaciones, como un lento inicio de acción, una inadecuada respuesta antidepresiva, disfunción sexual o tolerabilidad mejorable. En esta revisión analizaremos nuevos mecanismos fisiopatológicos implicados en la depresión como dianas para la búsqueda de antidepresivos diferentes. En el ámbito de la endocrinología los resultados son desalentadores, efímeros (TRH), limitados (hormonas tiroideas), dudosos (antagonistas CRH1), controvertidos (estrógenos) o poco eficaces (andrógenos). Varios neuropéptidos están implicados en la patogenia de la depresión, como la hormona antidiurética, la oxitocina, la sustancia P, el neuropéptido Y o la galanina, pero su abordaje desde el punto de vista terapéutico no ha dado resultados terapéuticos. La relación entre depresión y procesos inflamatorios es patente, pero los datos de eficacia, muchas veces anecdóticos, de algunos antiinflamatorios, antagonistas de TNF o anticuerpos monoclonales no pueden generalizarse. La participación del sistema opioide endógeno también se ha explorado, pero su potencial adictivo hace que no dispongamos en estos momentos “opioides antidepresivos”. La hipótesis glutamatérgica de la depresión ha sido trabajada durante más de 3 décadas y por fin parece que ha dado resultados: la esketamina, un isómero de la ketamina, ha demostrado, gracias a un programa de desarrollo clínico robusto, que es un antidepresivo de acción rápida, eficaz en depresión resistente, con una tolerabilidad aceptable, lo que ha motivado su autorización en depresión resistente en asociación con antidepresivos convencionales. La esketamina es la respuesta terapéutica a la “hipótesis glutamatérgica de la depresión”.
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