Effect of ketamine treatment on suicidality among severely depressed patients at high risk of suicide

Till date, several congeners of ketamine and routes of administration has been tried for treatment of depression with variable success. Esketamine (S-enantiomer of ketamine) nasal spray has also received US Food and Drug Administration (FDA) approval for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression) in the year 2018. While intravenous (IV) administration of ketamine has been widely regarded as the gold-standard treatment route, oral ketamine is preferred by many researchers over IV ketamine due to its better safety profile, enhanced accessibility and scalability. However, a group of researchers have also expressed concerns regarding reduced or loss of efficacy of ketamine via the oral route vis-a-vis the intravenous route. Bulk of this scientific literature (barring few case reports or small case series) is from western countries that might not be generalizable to the Indian population due to differences in the genetic makeup, ethnicity, and prevailing socio-cultural norms shown to influence depression symptom severity and response to treatment. This assumes even more importance, when dosing related decisions and the safety profile of a treatment needs to be determined. Thus, we plan to conduct this study to assess and compare the tolerability and effectiveness of oral and IV ketamine for treatment of suicidal ideation among patients with severe depression.