RESUMO
Objective@#To evaluate the long-term safety and efficacy of intranasal esketamine in patients with treatment-resistant depression from the Asian subgroup of the SUSTAIN-2 study. @*Methods@#SUSTAIN-2 was a phase 3, open-label, single-arm, multicenter study comprising a 4-week screening, 4-week induction, 48-week optimization/maintenance, and 4-week follow-up (upon esketamine discontinuation) phase. Patients with treatment-resistant depression received esketamine plus an oral antidepressant during the treatment period. @*Results@#The incidence of ≥ 1 serious treatment-emergent adverse event (TEAE) among the 78 subjects from the Asian subgroup (Taiwan: 33, Korea: 26, Malaysia: 19) was 11.5% (n = 9); with no fatal TEAE. 13 Asian patients (16.7%) discontinued esketamine due to TEAEs. The most common TEAEs were dizziness (37.2%), nausea (29.5%), dissociation (28.2%), and headache (21.8%). Most TEAEs were mild to moderate in severity, transient and resolved on the same day. Upon discontinuation of esketamine, no trend in withdrawal symptoms was observed to associate long-term use of esketamine with withdrawal syndrome. There were no reports of drug seeking, abuse, or overdose. Improvements in symptoms, functioning and quality of life, occurred during in the induction phase and were generally maintained through the optimization/maintenance phases of the study. @*Conclusion@#The safety and efficacy of esketamine in the Asian subgroup was generally consistent with the total SUSTAIN-2 population. There was no new safety signal and no indication of a high potential for abuse with the long-term (up to one year) use of esketamine in the Asian subgroup. Most of the benefits of esketamine occurred early during the induction phase.
RESUMO
This study explores responses to ketamine in patients with treatment-resistant depression (TRD) using a wearable forehead electroencephalography (EEG) device. We recruited and randomly assigned 55 outpatients with TRD into three approximately equal-sized groups (A: 0.5-mg/kg ketamine; B: 0.2-mg/kg ketamine; and C: normal saline) under double-blind conditions. The ketamine responses were measured by EEG signals and Hamilton depression rating scale scores. At baseline, the responders showed significantly weaker EEG theta power than the non-responders (p < 0.05). Compared to the baseline, the responders exhibited higher EEG alpha power but lower EEG alpha asymmetry and theta cordance post-treatment (p < 0.05). Furthermore, our baseline EEG predictor classified the responders and non-responders with 81.3 ± 9.5% accuracy, 82.1 ± 8.6% sensitivity, and 91.9 ± 7.4% specificity. In conclusion, the rapid antidepressant effects of mixed doses of ketamine are associated with prefrontal EEG power, asymmetry, and cordance at baseline and early post-treatment changes. Prefrontal EEG patterns at baseline may serve as indicators of ketamine effects. Our randomized double-blind placebo-controlled study provides information regarding the clinical impacts on the potential targets underlying baseline identification and early changes from the effects of ketamine in patients with TRD.
