Party drug to mainstream medicine; the transition of ketamine

A significant proportion of patients with major depressive disorder are refractory to approved interventions. The first report of significant and rapid benefit of intravenous (IV) ketamine for treatment resistant depression (TRD) appeared in 2000. Since then, there have been multiple reports on the efficacy and tolerability of ketamine formulations for TRD, in particular for single-dose IV administration, which is supported by meta-analyses. The benefit for oral and other non-IV forms remains preliminary. There is preliminary evidence that ketamine has anti-suicidal properties. The adverse effects of ketamine are often mild, brief, and not clinically significant, and include dissociation, sedation, and changes in blood pressure and heart rate. Recently, the S-enantiomer esketamine has been developed, evaluated, and approved for use in North America as adjunct to antidepressants for TRD. Intranasal esketamine has ease of use but the IV form has the advantage of cost. Both are equally effective and tolerable with few drug interactions, and are indicated for adult patients with TRD. Informed consent, medical assessment, supervised setting and monitoring by trained personnel are mandatory. The increased risk of misuse, diversion, and addiction has been recognized with the need for education, responsible practice, and ongoing research.