NMDA receptor antagonists for depression: Critical considerations

Gianluca Serafini, X. Gonda, Z. Ríhmer, Maurizio Pompili, Paolo Girardi, Henry A. Nasrallah, Mario Amore

Research output: Article

9 Citations (Scopus)


BACKGROUND: Research studies suggest that glutamate dysfunction, in particular N-methyl-d-aspartate receptors (NMDARs) abnormalities, may be involved in the pathophysiology of major neuropsychiatric conditions. Increased glutamatergic excitotoxic activity may be found in some brain circuits of patients with major depression. According to several published reports, NMDAR antagonists may exert antidepressant activity, but the molecular changes associated with abnormal glutamatergic neurotransmission remain unclear. METHODS: We have critically reviewed the current literature in order to investigate the role of NMDAR antagonists in major depression. RESULTS: NMDAR antagonists, such as ketamine, may be considered novel and promising pharmacological options for the rapid treatment of treatment-resistant depression patients. This is in contrast to the delayed action of the currently available antidepressant medications. Studies suggest that glutamatergic receptor modulation may enhance neuroplasticity mechanisms and neurogenesis together with the release of some neurotransmitters. Unfortunately, the use of ketamine is currently limited by some transient adverse events, including dissociative symptoms. CONCLUSIONS: Targeting NMDARs using antagonists represents an important alternative antidepressant option in major depression. However, NMDAR antagonists may exert different actions based on the differential brain location of NMDAR.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalAnnals of Clinical Psychiatry
Issue number3
Publication statusPublished - aug. 1 2015

ASJC Scopus subject areas

  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'NMDA receptor antagonists for depression: Critical considerations'. Together they form a unique fingerprint.

  • Cite this

    Serafini, G., Gonda, X., Ríhmer, Z., Pompili, M., Girardi, P., Nasrallah, H. A., & Amore, M. (2015). NMDA receptor antagonists for depression: Critical considerations. Annals of Clinical Psychiatry, 27(3), 213-220.