Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression

In this Phase II study (n=67), intranasal esketamine (3 doses evaluated) was superior to placebo in terms of change from baseline to day 8 in the Montgomery-Åsberg Depression Rating Scale total score (difference ranging from −4.2 to −9.0; dose-response relationship [P <0.001]).

This was the first clinical trial to evaluate intranasal esketamine hydrochloride (the more potent S-enantiomer of ketamine), as an adjunct to oral antidepressants, in treatment-resistant depression. The authors of a related editorial note its rapid effect (significant effect on the primary endpoint within one week), and discuss the advantages and disadvantages of intranasal delivery. The results of this early research are promising and support its further investigation; a Phase III study evaluating the necessary frequency of dosing and duration of effect is underway.