University of Ottawa Institute of Mental Health Research at The Royal, Ottawa, Ontario, Canada.
Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada.
Int J Neuropsychopharmacol. 2022 Dec 12;25(12):992-1002. doi: 10.1093/ijnp/pyac045.
Subanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment.
Thirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report.
Twenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37-0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η p2 = 0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P < .001, d = 2.00; Quick Inventory of Depressive Symptoms Self-Report item 10, P < .001, d = 1.36).
A short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier NCT01945047.
亚麻醉剂量的氯胺酮输注可以迅速产生持续的抗抑郁作用，但氯胺酮对认知的潜在影响尚未得到充分研究。本研究在一项评估单次和重复使用氯胺酮疗效的临床试验中，测量了重复氯胺酮治疗后客观和主观认知功能的变化。
38 名难治性抑郁症患者在接受 7 次静脉输注氯胺酮（0.5mg/kg，40 分钟）后，在临床试验中接受认知评估，氯胺酮输注。采用蒙哥马利-阿斯伯格抑郁评定量表（MADRS）和抑郁症状自评快速清单（Quick Inventory of Depressive Symptoms Self-Report）评估抑郁严重程度和感知注意力。
23 名患者（60.5%）在重复输注后（MADRS 总分下降≥50%）有反应。我们发现几个认知领域有显著改善，包括注意力、工作记忆、言语和视空间记忆（效应大小范围为 Cohen d=0.37-0.79）。认知变化归因于抑郁症状的减轻，除了言语记忆的改善，这在调整 MADRS 总分变化后仍然显著（P=0.029，η p2=0.13）。只有应答者报告重复氯胺酮给药后主观认知功能改善（MADRS 项目 6，P<0.001，d=2.00；抑郁症状自评快速清单项目 10，P<0.001，d=1.36）。
在难治性抑郁症患者中，短期重复氯胺酮输注不会损害神经认知功能。需要进一步研究以了解反应和缓解对伴随氯胺酮治疗的认知功能改善的潜在中介作用，以及检查长期安全性结果。临床试验注册编号 NCT01945047。
