Effect of S-ketamine on Depressed Patients Undergoing Electroconvulsive Therapy-a Randomized, Double-blind, Controlled Clinical Study

Nowadays, depression has become one of the serious mental diseases that affect human's life. With the acceleration of life pace and social pressure, the incidence of depression is increasing year-on-year. According to the statistics of the WHO, by 2017, there were more than 300 million people suffering from depression, accounting for 4.4% of the global population. Depression is highly related to suicide, which is an important reason for suicidal intention and attempt. It has been demonstrated that the incidence of suicide associated with major depression was as high as 15%. The main characteristic of depression is significant and lasting depression, which is caused by the decrease of monoamine transmitters (including dopamine, 5-HT, et al.) related to mood. In the past, antidepressants mainly relied on increasing or reducing the metabolism of transmitters, but these drugs usually took weeks or even months to take effect, and although the symptoms of depression were relieved within weeks after the start of treatment, they were still not ideal in the long term. Therefore, the drug treatment of depression is not optimistic.

Electroconvulsive therapy (ECT), as the first biological therapy introduced into psychiatry, has been improving with the progress of technology and equipment. More studies show that ECT is a safe and effective treatment, and the treatment of severe depression is the first choice in some cases. However, cognitive dysfunction, relapse tendency and related safety after ECT need further study.

Short acting sedatives and muscle relaxants before ECT can minimize the fear and muscle pain caused by ECT induced seizures. Previous sedatives used include propofol, mesaclopidol, thiopental and ketamine. Ketamine can be used for ECT anesthesia in patients with depression because of its good epileptic characteristics and prevention of cognitive dysfunction after ECT. More evidences reveal ketamine has strong antidepressant effect and reduces suicide of patients with treatment-resistant depression or mania. The low dose of ketamine can take effect within one hour, produce rapid antidepressant effect, and can play a role in more than 70% of patients with refractory depression. In addition, even a single intravenous injection of ketamine can effectively reduce the symptoms of depression within 24-72 hours, and may have synergistic antidepressant effect when combined with ECT. Although ketamine is considered to have a significant antidepressant effect in patients with depression, its application in mental disorders remains to be further explored because it may aggravate mental symptoms. However, some studies also found that ketamine did not significantly improve the effect of ECT on depression compared with other anesthetics.

Esketamine is the isomer of ketamine, which mainly acts on NMDA receptor of glutamate and its affinity to the receptor is 3-4 times that of ketamine, therefore it has stronger effect. Evidence suggests that esketamine can regulate NMDA receptor, increase the release of various neurotransmitters, improve the depression of patients, and repair the damaged neurons to improve the neuronal connections in the brain. As an anesthetic, the potency of esketamine is two times higher than ketamine, three times higher than R-ketamine, and its drug metabolism time is shorter, and the related side effects are also significantly reduced. Conseuqently, it has been widely used as an anesthetic in some countries. The efficacy and safety of esketamine nasal spray as a rapid and effective antidepressant in the treatment of patients with refractory depression have been confirmed. However the effect of intravenous esketamine as an anesthetic in ECT anesthesia on patients who are depressed remains unknown. The aim of this study is to evaluate the short-term effect and safety of esketamine as a adjunctive anesthetic in routine ECT anesthesia for patients with depression.