Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1)
The International Journal of Neuropsychopharmacology July 9, 2019 Maggie Fedgchin, Madhukar Trivedi, Ella J Daly et al. 593 citations
In a phase 3 trial of 346 adults with moderate-to-severe treatment-resistant depression, adding esketamine nasal spray (56 or 84 mg twice weekly) to a new oral antidepressant for 4 weeks did not significantly reduce depression scores compared to adding placebo nasal spray. The 84 mg dose failed to separate from placebo on the primary outcome, and the 56 mg dose could not be formally tested due to the statistical hierarchy. However, the magnitude of improvement with both esketamine doses exceeded what is typically considered clinically meaningful for approved antidepressants. Common side effects included nausea, dissociation, dizziness, vertigo, and headache. The authors conclude the results provide supportive evidence for esketamine's safety and efficacy in treatment-resistant depression.