Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Psychiatry Res. 2021 Aug;302:113993. doi: 10.1016/j.psychres.2021.113993. Epub 2021 May 13.
Ketamine may exert pro-cognitive effects on select measures of cognition in adults with mood disorders. We evaluated the effectiveness of intravenous (IV) ketamine on cognition in 68 adult outpatients with treatment-resistant depression (TRD) at the Canadian Rapid Treatment Center of Excellence between July 3, 2018 and April 16, 2020 (NCT04209296). Eligibility criteria for the present retrospective study included: primary diagnosis of major depressive or bipolar disorder; currently depressed; and insufficient response to two or more prior treatments. Participants received four infusions of ketamine hydrochloride (0.5-0.75 mg/kg) over 1-2 weeks. We assessed objective and subjective measures of cognition before and after two infusions, i.e., Digit Symbol Substitution Test (DSST), Trail Making Test-B (TMT-B), Patient Deficits Questionnaire, 5-item (PDQ-5-D). Ketamine significantly improved DSST (effect size [ES]=0.60), TMT-B (ES=0.84), as well as PDQ-5-D scores (ES=0.63), indicative of a moderate-to-large effect size. Improvements in DSST and PDQ-5-D with ketamine were mediated by reductions in depressive symptoms, whereas improvements in TMT-B were independent of changes in depressive symptoms. Our results support the independent, rapid-onset, pro-cognitive effects with IV ketamine in adults with TRD. Larger, randomized, controlled trials with ketamine wherein cognition is the primary outcome measure in mood and non-mood disorder samples are warranted.
氯胺酮可能对患有心境障碍的成年人的某些认知测量产生认知促进作用。我们在 2018 年 7 月 3 日至 2020 年 4 月 16 日期间，在加拿大快速治疗卓越中心评估了静脉内（IV）氯胺酮对 68 名患有治疗抵抗性抑郁症（TRD）的成年门诊患者认知的影响（NCT04209296）。本回顾性研究的入选标准包括：主要诊断为重度抑郁或双相情感障碍；目前抑郁；以及对两种或多种先前治疗反应不足。参与者接受了四个盐酸氯胺酮（0.5-0.75mg/kg）的输注，为期 1-2 周。我们在两次输注前后评估了认知的客观和主观测量，即数字符号替换测试（DSST）、连线测试 B（TMT-B）、患者缺陷问卷 5 项（PDQ-5-D）。氯胺酮显著改善了 DSST（效应大小[ES]=0.60）、TMT-B（ES=0.84）和 PDQ-5-D 评分（ES=0.63），表明存在中到大的效应大小。氯胺酮改善 DSST 和 PDQ-5-D 与抑郁症状的减少有关，而 TMT-B 的改善与抑郁症状的变化无关。我们的结果支持 IV 氯胺酮在 TRD 成人中的独立、快速起效、认知促进作用。需要进行更大规模、随机、对照试验，以评估氯胺酮在心境和非心境障碍样本中的认知作为主要结局指标的效果。
