The ketamine-related nasal spray esketamine is effective at relieving the symptoms of treatment-resistant depression, a phase III study published in the American Journal of Psychiatry has suggested (21 May 2019)
The trial involved 227 patients who were randomly assigned to intranasal esketamine 56mg or 84mg twice-weekly or placebo, plus an antidepressant. Depressive symptoms were measured on the Montgomery–Ã…sberg Depression Rating Scale (MADRS), with a mean score of 37 out of 60 in both groups at baseline.
At 28 days, the change in MADRS score was significantly greater in the esketamine group than in the placebo group at –21.4 versus –17.0, respectively. Adverse events, such as dizziness, dissociation, vertigo and nausea, were more common in the active treatment group.
Esketamine is structurally similar to ketamine, and is intended to mimic the drug’s rapid effects on depression while minimising side effects. The researchers said the results of this trial suggested that it could address an unmet need in this condition.
Co-author Michael Thase, professor of psychiatry at the University of Pennsylvania, Philadelphia, said: “The novel mechanism of action of esketamine, coupled with the rapidity of benefit, underpins just how important this development is for patients with difficult-to-treat depression.”
 Popova V, Daly E, Trivedi M et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psych 2019;176(6):428–438. doi: 10.1176/appi.ajp.2019.19020172