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
June 5, 2019
Ella Daly, Madhukar H. Trivedi, Adam Janik et al.
766 citations
For adults with treatment-resistant depression who achieved stable remission or response after 16 weeks of esketamine nasal spray plus an oral antidepressant, continuing esketamine plus the antidepressant delayed relapse significantly more than switching to placebo plus the antidepressant. Among those in stable remission, 26.7% relapsed on esketamine versus 45.3% on placebo, a 51% reduction in relapse risk. Among stable responders, 25.8% relapsed on esketamine versus 57.6% on placebo, a 70% reduction. Common side effects of esketamine included transient taste disturbance, vertigo, dissociation, drowsiness, and dizziness.
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.
The International Journal of Neuropsychopharmacology
July 9, 2019
Maggie Fedgchin, Madhukar H. Trivedi, Ella 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.
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.
Biological Psychiatry
November 4, 2015
Jaskaran Singh, Maggie Fedgchin, Ella Daly et al.
466 citations
A single 40-minute intravenous infusion of esketamine at either 0.20 mg/kg or 0.40 mg/kg produced a rapid and robust antidepressant effect in patients with treatment-resistant depression, with significant improvement in depression scores within two hours. The higher and lower doses were similarly effective, but the lower dose may offer better tolerability. Common side effects included headache, nausea, and transient dissociation that resolved within four hours.
The Journal of Clinical Psychiatry
April 20, 2020
Ewa Wajs, Leah Aluisio, Richard Holder et al.
288 citations
In a year-long open-label study of 802 adults with treatment-resistant depression, esketamine nasal spray combined with a new oral antidepressant showed a manageable safety profile and sustained improvement in depressive symptoms. Common side effects included dizziness, dissociation, nausea, and headache, mostly mild or moderate and resolving the same day. Two deaths occurred, neither linked to the drug. Cognitive performance remained stable or improved. Depression scores dropped during the first four weeks and stayed lower through the maintenance phase.
The Journal of Clinical Psychiatry
July 16, 2021
Ibrahim Turkoz, Ella Daly, Jaskaran Singh et al.
21 citations
For patients with treatment-resistant depression who did not show a response within the first week of treatment, a full four-week induction course of esketamine nasal spray plus an oral antidepressant may still provide benefit. In a pooled analysis of two phase 3 trials, among those not meeting early response criteria at day 2 or days 2 and 8, the odds of a response by day 28 were about 1.6 times higher with esketamine plus antidepressant compared to antidepressant plus placebo. The findings suggest that lack of early improvement does not preclude later benefit from the full induction course.
The International Journal of Neuropsychopharmacology
April 7, 2020
Michel Nijs, Ewa Wajs, Leah Aluisio et al.
21 citations
For patients with treatment-resistant depression, adjusting how often they use esketamine nasal spray based on their symptoms can help maintain or improve treatment response. In an open-label study of 778 patients, those who responded to twice-weekly esketamine during a 4-week induction phase then had their treatment frequency reduced to weekly. After four weeks of weekly treatment, 26% of 580 responders continued to improve, 50% maintained benefit, and 24% worsened. When frequency was further reduced to every other week, 19% improved, 49% maintained benefit, and 32% worsened. For patients who lost remission after reducing frequency, increasing back to weekly led to 47% improving, 43% staying the same, and 10% worsening. These results suggest that personalizing esketamine treatment frequency can optimize outcomes.
Psychiatry Research
March 15, 2023
Ibrahim Turkoz, J. Craig Nelson, Samuel T. Wilkinson et al.
19 citations
A post hoc analysis of two pooled 4-week phase 3 trials examined predictors of response and remission in patients with treatment-resistant depression receiving esketamine nasal spray plus a new oral antidepressant compared to a new oral antidepressant plus placebo nasal spray. Younger age, being employed, having fewer failed antidepressants in the current episode, and early reduction in Clinical Global Impression-Severity score at day 8 predicted better outcomes. Those on esketamine had 68% higher odds of response and 55% higher odds of remission. In the esketamine group, response was more likely in employed patients, those without baseline anxiety, and those with early symptom improvement.
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.
The International Journal of Neuropsychopharmacology
November 1, 2024
Randall L. Morrison, Jaskaran Singh, Ella Daly et al.
9 citations
In patients with treatment-resistant depression, adding esketamine nasal spray to a newly initiated oral antidepressant did not harm cognitive function over the short or long term. Across three short-term double-blind studies (747 patients aged 18–64 years) and one long-term maintenance study (137 patients aged 65 or older), cognitive performance on tests of psychomotor function, attention, and memory either remained stable or slightly improved from baseline to the end of treatment. At the start, patients showed mild-to-moderate cognitive impairment. The correlation between depression severity and cognitive performance was weak. The analysis found no evidence that esketamine worsens cognition in treatment-resistant depression.
CNS Spectrums
February 1, 2018
Abigail I. Nash, M. Shawi, Jaskaran Singh et al.
In a post-hoc analysis of a Phase 2a clinical trial, adults with treatment-resistant major depressive disorder who had not responded to at least two prior antidepressants received twice-weekly intranasal esketamine (28 mg, 56 mg, or 84 mg) or placebo for one week. At all doses, patients reported a one-point average improvement on the Patient Global Impression Severity scale, while placebo patients reported no change. Clinician ratings on the Clinical Global Impression Severity scale similarly improved for esketamine groups but not for placebo. These results suggest that esketamine can produce clinically meaningful improvement in depression symptoms within one week, as reported by both clinicians and patients, consistent with prior findings using the Montgomery-Åsberg Depression Rating Scale.