Johnson Danica E, Rodrigues Nelson B, Weisz Sydney, Chisamore Noah, Kaczmarek Erica S, Chen-Li David C J, Doyle Zoe, Richardson J Don, Mansur Rodrigo B, McIntyre Roger S, Rosenblat Joshua D
Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, Toronto Western Hospital - University Health Network, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, Toronto Western Hospital - University Health Network, Toronto, ON, Canada; Department of Psychology, Neuropsychology Track, University of Windsor, Windsor, ON, Canada.
Eur Neuropsychopharmacol. 2025 Feb;91:69-77. doi: 10.1016/j.euroneuro.2024.11.008. Epub 2024 Dec 5.
Depression with comorbid posttraumatic stress disorder (PTSD) is associated with more severe symptoms and a reduced response to traditional treatments. Although ketamine shows promise as a rapid-acting antidepressant for treatment-resistant depression (TRD), its effectiveness in patients with comorbid PTSD remains underexplored. Therefore, we conducted a retrospective analysis of 134 patients from the Canadian Rapid Treatment Center of Excellence to compare the effectiveness of four ketamine infusions (0.5-0.75 mg/kg) in reducing symptoms of depression and PTSD in TRD patients with and without comorbid PTSD. A repeated-measures linear mixed model was used to evaluate the impact of comorbid PTSD on ketamine's antidepressant effectiveness, measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Paired samples t-tests were used to assess changes in PTSD symptoms, measured by the PTSD Checklist for DSM-5 (PCL-5). We found a significant main effect of time on QIDS-SR16 scores, F(4, 209.32) = 36.67, p < 0.001, but no significant group-by-time interaction (p = 0.895), suggesting that comorbid PTSD did not impact the antidepressant effectiveness of ketamine. Significant improvements in PTSD symptoms were observed in overall PCL-5 scores, t(66) = 6.66, p < 0.001, and across all PCL-5 symptom clusters with moderate to large effect sizes. In a real-world sample of TRD patients, ketamine was effective in reducing symptoms of depression and PTSD, regardless of PTSD comorbidity. These findings highlight ketamine's potential as a novel intervention for a patient population that is frequently non-responders to conventional treatments. Future randomized controlled trials should explore mediating factors of improvement and long-term effects.
伴有创伤后应激障碍（PTSD）的抑郁症与更严重的症状以及对传统治疗反应降低有关。尽管氯胺酮有望成为治疗难治性抑郁症（TRD）的速效抗抑郁药，但其在伴有PTSD的患者中的有效性仍未得到充分研究。因此，我们对来自加拿大卓越快速治疗中心的134例患者进行了回顾性分析，以比较四次氯胺酮输注（0.5 - 0.75mg/kg）在减轻伴有和不伴有PTSD的TRD患者的抑郁和PTSD症状方面的有效性。采用重复测量线性混合模型，通过抑郁症状快速自评量表（QIDS - SR16）评估共病PTSD对氯胺酮抗抑郁效果的影响。配对样本t检验用于评估PTSD症状的变化，通过DSM - 5的PTSD检查表（PCL - 5）进行测量。我们发现时间对QIDS - SR16评分有显著的主效应，F(4, 209.32) = 36.67，p < 0.001，但没有显著的组×时间交互作用（p = 0.895），这表明共病PTSD不会影响氯胺酮的抗抑郁效果。在总体PCL - 5评分中观察到PTSD症状有显著改善，t(66) = 6.66，p < 0.001，并且在所有PCL - 5症状簇中都有中等到较大的效应量。在TRD患者的真实世界样本中，无论是否合并PTSD，氯胺酮在减轻抑郁和PTSD症状方面均有效。这些发现凸显了氯胺酮作为一种新干预措施对经常对传统治疗无反应的患者群体的潜力。未来的随机对照试验应探索改善的中介因素和长期效果。
