Monoaminergic system and depression
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Major depressive disorder is a severe, disabling disorder that affects around 4.7% of the population worldwide. Based on the monoaminergic hypothesis of depression, monoamine reuptake inhibitors have been developed as antidepressants and nowadays, they are used widely in clinical practice. However, these drugs have a limited efficacy and a slow onset of therapeutic action. Several strategies have been implemented to overcome these limitations, including switching to other drugs or introducing combined or augmentation therapies. In clinical practice, the most often used augmenting drugs are lithium, triiodothyronine, atypical antipsychotics, buspirone, and pindolol, although some others are in the pipeline. Moreover, multitarget antidepressants have been developed to improve efficacy. Despite the enormous effort exerted to improve these monoaminergic drugs, they still fail to produce a rapid and sustained antidepressant response in a substantial proportion of depressed patients. Recently, new compounds that target other neurotransmission system, such as the glutamatergic system, have become the focus of research into fast-acting antidepressant agents. These promising alternatives could represent a new pharmacological trend in the management of depression.
KeywordsAntidepressant Major depression Monoamines Augmentation Multitarget agents
This work was supported by grants from the “Ministerio de Economía y Competitividad” (MINECO), co-financed by “Fondo Europeo de Desarrollo Regional” FEDER “A way to build Europe” (SAF2015-68647-R; “Instituto de Salud Carlos III (PI12/00915, PI18/01691)); the “Centro de Investigación Biomédica en Red de Salud Mental-CIBERSAM” (Spain; CB/07/09/0033); the “Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía” (Spain; CTS-510 and CTS-7748); the “Consejería de Salud de la Junta de Andalucía” (Spain; PI-0134-2018); the “Fundación Progreso y Salud de la Junta de Andalucía” (PI-0080-2017); and a 2015 NARSAD Young Investigator Grant from the Brain Behavior Research Foundation (NARSAD 23982).
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Conflict of interest
The authors declare that they have no conflict of interest.
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