Ketamine as antidepressant? Current state and future perspectives

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.