Novel Pathways in the Treatment of Major Depression: Focus on the Glutamatergic System.

Maurizio Pompili, Domenico D Berardis, Michele Fornaro, Marco D Nicola, Yong-Ku Kim, Massimo D Giannantonio, Giovanni Martinotti, Federica Vellante, Giampaolo Perna, Gianluca Serafini, Antonio Ventriglio, Alessandro Carano, Alessandro Valchera, Laura Orsolini, Cristina Santone, Annastasia L C Fiengo, Chiara Montemitro, Carmine Tomasetti, Antonello Bellomo

Journal: Current pharmaceutical design 2020;25(4):381-387

PMID: 30864501

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Abstract

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further "neurobiological targeted" approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.

Address: NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital "Maria SS dello Splendore", Giulianova, Italy.; Polyedra Research Group, Teramo, Italy.; Department of Psychiatry, University Medical School "Federico II", Naples, Italy.; Department of Neuroscience, Imaging and Clinical Science, University "G. D'Annunzio", Chieti, Italy.; NHS, Department of Mental Health ASUR Marche AV5, Mental Health Unit, Ascoli Piceno, Italy.; School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, United Kingdom.; Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy.; Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso," NHS, San Benedetto del Tronto, Ascoli Piceno, Italy.; Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, S. Andrea Hospital, Sapienza University, Rome, Italy.; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.; Department of Clinical Neurosciences, Hermanas Hospitalarias, Villa San Benedetto Menni Hospital, FoRiPsi, Albese con Cassano, Como, Italy.; Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.; Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, Miami University, Miami, United States.; Department of Psychiatry, Korea University College of Medicine, Seoul, Korea.; Institute of Psychiatry and Psychology, Catholic University of Sacred Heart, Rome, Italy.; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.; NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", Teramo, Italy.

DOI: 10.2174/1381612825666190312102444

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MeSH Terms: Depression, Depressive Disorder, Major, Excitatory Amino Acid Agents, Glutamic Acid, Humans, Ketamine, Synaptic Transmission