American Journal of Psychiatry
May 21, 2019
Vanina Popova, Ella J. Daly, Madhukar Trivedi et al.
879 citations
Switching to esketamine nasal spray plus a new antidepressant led to a significantly greater reduction in depression severity after 28 days than switching to a new antidepressant alone in adults with treatment-resistant depression. The average improvement on the Montgomery-Åsberg Depression Rating Scale was 4 points greater with esketamine (95% CI -7.31 to -0.64). Earlier improvements were also seen. Common side effects included dissociation, nausea, vertigo, dysgeusia, and dizziness, which typically appeared shortly after dosing and resolved within 1.5 hours. Seven percent of esketamine patients discontinued due to adverse events versus 0.9% in the comparator group. The findings support esketamine as a rapidly acting option for this difficult-to-treat population.
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.
CNS spectrums
June 1, 2024
Jennifer Kern Sliwa, Ronaldo R Naranjo, Ibrahim Turkoz et al.
5 citations
In adults with treatment-resistant depression, adding esketamine nasal spray to a newly initiated oral antidepressant led to greater improvement in depressive symptoms than oral antidepressant plus placebo spray. Across two short-term trials, the group receiving esketamine plus oral antidepressant showed a mean reduction of 12.8 points on the Patient Health Questionnaire-9 (PHQ-9) at 28 days, compared with 10.3 points in the placebo group, a statistically significant difference. 77.1% of patients in the esketamine group achieved a clinically meaningful improvement (at least a 6-point drop) versus 64% in the placebo group. In a separate relapse-prevention study, 57.3% of patients on esketamine plus oral antidepressant maintained remission (PHQ-9 score ≤4) versus 44.2% on oral antidepressant plus placebo. The self-reported PHQ-9 results aligned with clinician-rated Montgomery-Åsberg Depression Rating Scale scores.