American Journal of Psychiatry
May 21, 2019
Vanina Popova, Ella Daly, Madhukar H. 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.
JAMA Psychiatry
December 27, 2017
Ella Daly, Jaskaran Singh, Maggie Fedgchin et al.
708 citations
In adults with treatment-resistant depression, intranasal esketamine at doses of 28 mg, 56 mg, and 84 mg produced a rapid, dose-related reduction in depressive symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale. The improvement appeared to persist for more than two months even when dosing frequency was reduced. Adverse events leading to discontinuation occurred in 5% of esketamine-treated participants during the double-blind phase and in 2% during the open-label phase, with no such events in the placebo group.
American Journal of Psychiatry
April 8, 2016
Jaskaran Singh, Maggie Fedgchin, Ella Daly et al.
530 citations
In adults with treatment-resistant depression, intravenous ketamine (0.5 mg/kg) given two or three times per week produced a substantial and similar reduction in depression scores over 15 days compared to placebo. The twice-weekly ketamine group showed an average 18.4-point drop on the Montgomery-Åsberg Depression Rating Scale, versus 5.7 points for placebo; the thrice-weekly group showed a 17.7-point drop, versus 3.1 points for placebo. Headache, anxiety, dissociation, nausea, and dizziness were common side effects, but dissociative symptoms were temporary and lessened with repeated doses.
Journal of Affective Disorders
November 14, 2020
Stacie Hudgens, Lysbeth Floden, Michael Blackowicz et al.
77 citations
For patients with treatment-resistant depression (TRD)—those who have not responded to at least two different antidepressants in their current episode—meaningful improvement on two common depression scales was defined using a clinician-rated severity anchor. On the Patient Health Questionnaire (PHQ-9), a decrease of 6 points was the most appropriate meaningful change threshold. By Day 28, 86.5% of patients receiving esketamine nasal spray plus an antidepressant reached or exceeded this threshold, compared to 70% of those receiving placebo plus an antidepressant. On the Montgomery-Åsberg Depression Rating Scale (MADRS), a decrease of 10 points was the most appropriate threshold, with 78.2% of esketamine-treated patients versus 65.0% of placebo-treated patients meeting it. These anchor-based thresholds help interpret individual-level treatment response in TRD.
Health and Quality of Life Outcomes
May 8, 2023
Carol Jamieson, Vanina Popova, Ella Daly et al.
18 citations
Patients with treatment-resistant depression who received esketamine nasal spray plus an oral antidepressant reported greater improvements in health-related quality of life and daily functioning after 28 days compared to those who received a placebo nasal spray plus an antidepressant. At day 28, a lower percentage of patients in the esketamine group reported problems across all five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The esketamine group also showed larger average improvements in health status index and overall health rating, as well as greater reductions in functional disability.