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.
Psychopharmacology
February 1, 2018
Randall L. Morrison, Maggie Fedgchin, Jaskaran Singh et al.
72 citations
Intranasal esketamine temporarily impairs cognitive performance and increases mental effort and sleepiness in healthy participants. At 40 minutes after dosing, performance on five cognitive tests (Detection, Identification, One-Card Learning, One Back, and Groton Maze Learning) was significantly worse compared with placebo. These effects resolved by 2 hours postdose, with no differences between esketamine and placebo at 2, 4, or 6 hours. Participants reported greater mental effort at 40 minutes and increased sleepiness at 40 minutes and 2 hours, which also returned to placebo levels later. Common mild adverse events included dizziness, nausea, attention disturbance, and fatigue.
Scientific Reports
July 28, 2020
Qingqin S. Li, Ewa Wajs, Rachel Ochs-Ross et al.
49 citations
A genome-wide association study in 527 people of European ancestry with major depressive disorder identified a significant genetic locus in the IRAK3 gene and a significant gene-level association in NME7 linked to the antidepressant efficacy of esketamine nasal spray, measured as percentage change in symptom severity. Polygenic risk score analysis showed the strongest association with esketamine efficacy came from genetic loading for depressive symptoms, though this did not reach study-wide significance. Suggestive signals were enriched in pathways related to neuronal and synaptic function, immune signaling, and glucocorticoid receptor/stress response.
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.
The International Journal of Neuropsychopharmacology
December 14, 2022
David Williamson, Ibrahim Turkoz, Ewa Wajs et al.
11 citations
Dissociation encompasses distinct phenomena, some linked to esketamine treatment and potentially overlapping with psychosis symptoms. In a post hoc analysis of data from an open-label, phase 3 study of esketamine plus a newly initiated oral antidepressant in patients with treatment-resistant depression, dissociation was reported as an adverse event in 14.3% (109/764) of patients. CADSS scores generally aligned with investigator-reported dissociation severity, but no cutoff point reliably distinguished presence from absence of dissociation events. Hallucinations occurred in 5 patients, and no delusions were reported, indicating psychotic symptoms were uncommon.