Zhang Sijia, Afshar Houtan, Colvonen Peter J, Nokes Brandon, Compton Jason, Mishra Jyoti, Bismark Andrew W, Ramanathan Dhakshin S, Koloski Miranda F
VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA.
Department of Psychiatry, UC San Diego, 3120 Biomedical Sciences Way, La Jolla, CA, 92093, USA.
CNS Drugs. 2025 Jun;39(6):609-619. doi: 10.1007/s40263-025-01180-w. Epub 2025 Apr 26.
Ketamine and esketamine are increasingly used to manage treatment-resistant depression and have also been shown to reduce symptoms of posttraumatic stress disorder (PTSD). Little is known about how common comorbidities in the veteran population, such as traumatic brain injury (TBI) or obstructive sleep apnea (OSA), may influence ketamine and esketamine treatment outcomes.
In this retrospective study, we analyzed clinical outcomes from Veterans Affairs (VA) San Diego Healthcare System's ketamine program to assess the relationship between ketamine or esketamine treatment and changes in depression and PTSD symptoms, while also examining how common medical comorbidities influence treatment outcomes. We specifically examined whether a patient's history of TBI or OSA would affect ketamine or esketamine treatment outcomes. Linear mixed-effects models were used to examine how TBI and OSA history interacted with ketamine/esketamine treatment to change PTSD Checklist for DSM-5 (PCL-5) and Patient Health Questionnaire-9 (PHQ-9) scores.
This study included 119 veterans who received eight sessions of ketamine or esketamine treatment at the San Diego VA Medical Center. Using linear effects modeling, we found that repeated ketamine or esketamine sessions were significantly correlated with reductions in both depression (p < 0.005) and PTSD (p < 0.05) symptom scores. However, in veterans with comorbid TBI (n = 38) and severe OSA (n = 9), depression symptoms did not improve over the course of ketamine or esketamine treatment, suggesting this subgroup may require alternative treatments or OSA treatment prior to starting ketamine or esketamine treatment.
Ketamine and esketamine treatment did not improve symptoms of depression in veterans with comorbid TBI and severe OSA. Thus, our findings generally support ketamine and esketamine as effective interventions for depression and PTSD, while emphasizing the consideration of comorbidities such as OSA and TBI.
氯胺酮和艾司氯胺酮越来越多地用于治疗难治性抑郁症，并且已被证明可减轻创伤后应激障碍（PTSD）的症状。对于退伍军人中常见的合并症，如创伤性脑损伤（TBI）或阻塞性睡眠呼吸暂停（OSA），如何影响氯胺酮和艾司氯胺酮的治疗效果，人们知之甚少。
在这项回顾性研究中，我们分析了退伍军人事务部（VA）圣地亚哥医疗保健系统氯胺酮项目的临床结果，以评估氯胺酮或艾司氯胺酮治疗与抑郁和PTSD症状变化之间的关系，同时研究常见的内科合并症如何影响治疗效果。我们特别研究了患者的TBI或OSA病史是否会影响氯胺酮或艾司氯胺酮的治疗效果。使用线性混合效应模型来研究TBI和OSA病史如何与氯胺酮/艾司氯胺酮治疗相互作用，以改变DSM-5创伤后应激障碍检查表（PCL-5）和患者健康问卷-9（PHQ-9）的得分。
本研究纳入了119名在圣地亚哥VA医疗中心接受八次氯胺酮或艾司氯胺酮治疗的退伍军人。通过线性效应模型，我们发现重复使用氯胺酮或艾司氯胺酮治疗与抑郁症状（p < 0.005）和PTSD症状（p < 0.05）得分的降低显著相关。然而，在合并TBI（n = 38）和重度OSA（n = 9）的退伍军人中，在氯胺酮或艾司氯胺酮治疗过程中抑郁症状并未改善，这表明该亚组在开始氯胺酮或艾司氯胺酮治疗之前可能需要替代治疗或OSA治疗。
氯胺酮和艾司氯胺酮治疗对合并TBI和重度OSA的退伍军人的抑郁症状没有改善作用。因此，我们的研究结果总体上支持氯胺酮和艾司氯胺酮作为治疗抑郁症和PTSD的有效干预措施，同时强调需要考虑OSA和TBI等合并症。
