Ketamine and electroconvulsive therapy pairing in depression and mood disorders

Although a number of medications are available for treatment of depressive disorders, one of the major limitations of all present antidepressants is delayed onset of action. In addition, despite recent advances in the pharmacological and non-pharmacological treatment of major depressive disorder, almost one third of patients fail to respond to any treatments. In recent years, one of the efforts to overcome the current limitations in treatment of depression has been to administer intravenous ketamine. Studies showing a rapid-onset antidepressant effect for the anesthetic agent ketamine, N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, in patients with treatment-resistant depression (TRD), have stimulated a new wave of pre-clinical and clinical research focused on the glutamate system and the NMDA receptor complex in mechanisms in major depressive disorder. A series of studies showed that chronic- but not acute, administration of several antidepressants, including imipramine, the serotonin-selective reuptake inhibitor citalopram and electroconvulsive therapy (ECT) in rats produced dose-dependent and persistent changes in the binding profile of NMDA receptors [2]. These findings suggested that adaptive changes in NMDA receptors might be a final common pathway for antidepressant action.