Ketamine as Antidepressant? Current State and Future Perspectives

Abstract

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.

Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression

“…Recent evidence strongly suggests that ketamine produces a rapid‐onset antidepressant effect in humans with major depressive disorder (MDD) . This commentary focuses on the evidence for the efficacy of ketamine as a rapid‐onset antidepressant and the implications of its mechanism of action for yielding insight into the biochemical basis of MDD.…”

La ketamina come antidepressivo ad azione rapida: controversia e implicazioni [translation of “Ketamine as a rapid antidepressant: the debate and implications” by Dr. Giacomo Galli and Dr. Serena Saraceni]

“…Gli antidepressivi correntemente utilizzati sono associati a una scarsa risposta e a una mancanza di efficacia clinica (Murrough 2012;Thakurta 2012;Hasselmann 2014).…”

Epigenetic Mechanisms of Serotonin Signaling

“…Thus, preliminary data suggest that previous exposure of schizophrenia patients to chronic treatment with atypical antipsychotic drugs, such as olanzapine and risperidone, prevents the therapeutic effects of LY404039, whereas this mGlu2/3 receptor agonist induces antipsychotic effects in patients previously treated with typical antipsychotics, such as haloperidol, that separate from placebo. 90 In addition, a genetic association between SNPs in the 5-HT 2A ( Htr2a ) gene and the response to LY404039 treatment has been demonstrated. 91 Further preclinical and clinical investigation is definitely needed to validate the molecular mechanisms underlying these effects of typical versus atypical antipsychotic drug treatment on therapeutic responses to LY404039.…”