For patients with depression response to treatment is rather unpredictable, slow in onset, and incomplete in success rate. Stepwise protocolled treatment fails to achieve a clinically meaningful response in approximately 30% of patients with depression. Professional guidelines advise electroconvulsive therapy (ECT) as the final treatment step for patients with TRD. ECT, however, entails considerable disadvantages: the procedure requires repeated anaesthesia and clinical admission, there is a risk of persistent and significant cognitive side effects, and 40% of patients relapse within six months. Hence, there is a pressing need for efficacious alternatives for patients with TRD. Esketamine appears to have robust immediate results on the reduction of depressive symptoms. Oral formulation of esketamine can be used for longer periods of time and is safe to use at home but is not yet registered for use in depression. Given its promising effects and presumed advantages, an important question is whether oral esketamine may serve as an effective and acceptable alternative to ECT.