Department of Psychiatry & Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, United States of America; Mental Health Service Line, Minneapolis VA Health Care System, Minneapolis, MN, United States of America.
Department of Psychiatry & Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, United States of America; Geriatric Research Education and Clinical Center, Minneapolis VA Health Care System, Minneapolis, MN, United States of America.
J Affect Disord. 2022 Jul 1;308:289-297. doi: 10.1016/j.jad.2022.04.066. Epub 2022 Apr 14.
The glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine rapidly ameliorates posttraumatic stress disorder (PTSD) and depression symptoms in individuals with comorbid PTSD and major depressive disorder (MDD). However, concerns over ketamine's potential neurocognitive side effects have yet to be assessed in this population. The current study investigated 1) changes in neurocognitive performance after a repeated ketamine dosing regimen and 2) baseline neurocognitive performance as a predictor of ketamine treatment effect.
Veterans with comorbid PTSD and MDD (N = 15) received six infusions of 0.5 mg/kg ketamine over a 12-day period. Neurocognitive and clinical outcomes assessments occurred at baseline and within 7 days of infusion-series completion using the CogState battery.
Repeated ketamine infusions did not significantly worsen any measures of cognition. Rather, significant improvement was observed in working memory following completion of the infusion series. In addition, greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set shifting at baseline. Lower verbal learning was also predictive of improvement in depression.
This study applied an open-label design without a placebo control. As such, it is not known to what extent the correlations or improvement in neurocognitive performance may have occurred under placebo conditions.
This is the first study to examine the neurocognitive effects of repeated ketamine in participants with comorbid PTSD and MDD. Our findings suggest potential baseline neurocognitive predictors of ketamine response for comorbid PTSD and MDD symptoms.
谷氨酸 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂氯胺酮可迅速改善伴有创伤后应激障碍（PTSD）和重性抑郁障碍（MDD）共病的个体的 PTSD 和抑郁症状。然而，在这一人群中，氯胺酮潜在的神经认知副作用仍有待评估。本研究调查了 1）重复氯胺酮给药方案后神经认知表现的变化，以及 2）基线神经认知表现作为氯胺酮治疗效果预测因子。
患有 PTSD 和 MDD 共病的退伍军人（N=15）在 12 天内接受了 6 次 0.5mg/kg 氯胺酮输注。在基线和输注系列完成后 7 天内，使用 CogState 电池进行神经认知和临床结果评估。
重复氯胺酮输注并未显著恶化任何认知测量指标。相反，在输注系列完成后，工作记忆显著改善。此外，PTSD 和 MDD 症状的改善与基线时工作记忆、处理速度较慢和定势转移较快有关。较低的言语学习也预测了抑郁的改善。
本研究采用开放标签设计，没有安慰剂对照。因此，尚不清楚在安慰剂条件下，神经认知表现的相关性或改善在多大程度上发生。
这是第一项研究重复氯胺酮在伴有 PTSD 和 MDD 共病的参与者中对神经认知的影响。我们的研究结果表明，对于 PTSD 和 MDD 症状，存在潜在的基线神经认知预测因子与氯胺酮反应相关。
