Could ketamine be the answer to treating treatment-resistant major depressive disorder?

Abstract

Major depressive disorder (MDD) is a common, serious, debilitating condition affecting 350 million people worldwide, which remains to be unsatisfactorily treated with 53% of patients still complaining of symptoms after completing their courses with the correct dosage. Ketamine, which was approved by the Food and Drug Administration in 2019, is a potential treatment option for those recalcitrant cases. The mechanism of ketamine is not fully understood, but as type it is classified as an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, and can be given intravenously, intranasally and orally. It is used to treat treatment-resistant depression, depression associated with suicidal ideation, mood and anxiety disorders and depressions associated with either type of bipolar disorder. Although ketamine is considered relatively safe, several side effects have been reported with the major ones being psychiatric in the form of worsening mood, anxiety and agitation; psychotomimetic in the form of dissociation, perceptual disturbance and abnormal sensations; cardiovascular in the form of increased blood pressure and increased heart rate; and neurological in the form of headache and dizziness. Ketamine is still not approved worldwide for usage in patients with treatment-resistant MDD, but if it is approved sometime in the future with relatively fewer side effects, it is expected to significantly save millions of dollars spent yearly on patients with treatment-resistant depression and that will lift this major burden off the shoulders of healthcare professionals. This study was designed to measure the effects of ketamine, an NMDA receptor antagonist, on patients with treatment-resistant MDD and to analyse the concept that makes it different and relatively safer than other major antidepressants like selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and TCAs (tricyclic antidepressants).