Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial
Hu, Z., Lan, X-F., Li, W., Liu, H., Mai, S., Ning, Y-P., Wang, C-Y., Ye, Y., Zhang, F., Zhou, Y-L.
This randomised-controlled trial (n=51) assessed the short-term effects of three subanesthetic esketamine infusions (17.5mg/70kg) in adolescents aged 13-18 with major depressive disorder (MDD) and suicidal ideation. The study found a significant improvement in processing speed and working memory in the esketamine group from baseline to days 6 and 12, with no harm to cognition observed. However, there was no significant association between baseline cognition and the antidepressant or antisuicidal effects of esketamine.
Abstract
Background: Ketamine and its enantiomer have rapid and robust effects on depressive symptom and suicidal ideation. Little is known about their cognitive effects in adolescents. We aimed to evaluate the short-term effect of esketamine on cognition in adolescents with major depressive disorder (MDD) and suicidal ideation.Method: In this randomized-controlled trial, 51 participants aged 13-18 with MDD and suicidal ideation received three intravenous infusions of either esketamine (0.25 mg/kg) or midazolam (0.02 mg/kg). Four dimensions of the MATRICS Consensus Cognitive Battery (MCCB), including processing speed, working memory, verbal learning and visual learning, were assessed at Days 0, 6 and 12.Results: In the linear mixed model, a significant time main effect (F = 12.803, P < 0.001), drug main effect (F = 6.607, P = 0.013), and interaction effect (F = 3.315, P = 0.041) was found in processing speed. Other dimensions including working memory and verbal learning showed significant time main effect (all P < 0.05), but no significant drug or interaction effect (all P > 0.05). Esketamine group showed improvement in processing speed from baseline to Days 6 and 12, and working memory from baseline to Day 12 (all P < 0.05). The generalized estimation equation showed no significant association between baseline cognition and antidepressant or antisuicidal effect (both P > 0.05).Conclusions: The present study suggested that three-dose subanesthetic esketamine infusions did not harm cognition among adolescents with MDD and suicidal ideation. Instead, esketamine may be associated with improvement in processing speed.