Research library / Clinical trial
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
Popova V, Daly EJ, Trivedi M, et al. American Journal of Psychiatry 2019;176(6):428-438
This phase 3 trial tested esketamine nasal spray, the drug later sold as Spravato, in 227 adults whose depression had not improved after at least two antidepressants. All switched to a new oral antidepressant; half also used esketamine spray twice a week and half a placebo spray. After four weeks, depression scores had improved by 4 points more in the esketamine group, with improvement visible earlier too. Dissociation, nausea, dizziness and similar side effects were more common with esketamine but usually passed within 90 minutes of a dose. The authors conclude that esketamine is an effective, rapidly acting option for treatment-resistant depression.
What it found
- At day 28, depression scores (MADRS) improved by 4.0 points more with esketamine than with placebo spray (95% CI -7.31 to -0.64)
- Dissociation, nausea, vertigo, altered taste and dizziness were more common with esketamine; they generally appeared shortly after dosing and resolved by 1.5 hours
- 7% stopped esketamine because of an adverse event, against 0.9% on placebo spray