Major depressive disorder (MDD) is a serious mental disorder that ranks among the major causes of disease
burden. Standard medical treatment targeting cerebral monoamines often provides only insufficient symptom relief and
fails in approximately every fifth patient. The complexity of MDD therefore, reflects more than monoaminergic
dysregulation. Initial research argues the case for excessive glutamate levels, suggesting that antiglutamatergic drugs
might be useful in treating MDD. Ketamine is a non-selective, high-affinity N-methyl-D-aspartate receptor (NMDAR)
antagonist most commonly used in pediatric and animal surgery. In the past, ketamine has gained popularity because of its
ability to rapidly elevate mood, even in treatment-resistant and bipolar depression. However, there are still many obstacles
before widespread clinical approval of ketamine treatment could become reality. In this review, ketamine’s powerful
antidepressant effects are discussed and further research necessary for therapeutic application is outlined. NMDAR
antagonists provide an entirely new way of treating the manifold appearances of depression that should not be left unused.
Keywords: Antidepressants, glutamate, ketamine, major depression, monoamines, NMDAR.
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