Esketamine for treatment resistant depression

On 5 March 2019 the US Food and Drug Administration approved esketamine nasal spray in conjunction with an oral antidepressant for people with treatment resistant depression. Esketamine is a form of ketamine.

Definitions of treatment resistant depression vary; one accepted definition is lack of response to two or more antidepressants. The burden of illness associated with this condition is substantial: major depressive disorder is the leading cause of years lost to disability worldwide, and 10-20% of people with major depression have illness resistant to treatment.1

Adjunctive psychotherapy can be effective in depression that has not responded to initial antidepressants. But lack of placebo controlled trials and less stringent inclusion criteria make extrapolation to treatment resistant depression, as defined above, difficult.2 Other effective options such as transcranial magnetic stimulation and electroconvulsive therapy are underused.3 New treatments are clearly needed.

Ketamine was first synthesised in 1962 as a safer analogue of the anaesthetic phencyclidine. It was initially used in psychiatry as a drug …