Abstract | BACKGROUND: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate ( NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. OBJECTIVE: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. METHODS: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. RESULTS:
Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. CONCLUSION: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.
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Authors | Domenico De Berardis, Carmine Tomasetti, Maurizio Pompili, Gianluca Serafini, Federica Vellante, Michele Fornaro, Alessandro Valchera, Giampaolo Perna, Umberto Volpe, Giovanni Martinotti, Silvia Fraticelli, Massimo Di Giannantonio, Yong-Ku Kim, Laura Orsolini |
Journal | Current topics in medicinal chemistry
(Curr Top Med Chem)
Vol. 20
Issue 7
Pg. 554-584
( 2020)
ISSN: 1873-4294 [Electronic] United Arab Emirates |
PMID | 32003691
(Publication Type: Journal Article, Systematic Review)
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Copyright | Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. |
Chemical References |
- Antidepressive Agents
- Receptors, N-Methyl-D-Aspartate
- Glutamic Acid
- Esketamine
- Ketamine
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Topics |
- Administration, Intranasal
- Antidepressive Agents
(administration & dosage, pharmacokinetics)
- Clinical Trials as Topic
- Databases, Factual
- Depression
(drug therapy)
- Depressive Disorder, Major
(drug therapy)
- Drug Compounding
- Glutamic Acid
(pharmacology)
- Humans
- Ketamine
(administration & dosage, pharmacokinetics, pharmacology)
- Receptors, N-Methyl-D-Aspartate
(metabolism)
- Synaptic Transmission
(drug effects)
- Time Factors
- Treatment Outcome
- United States
- United States Food and Drug Administration
- Suicide Prevention
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