Hossein Shabnam, Rengasamy Manivel, Uzamere Aiyedun, Spotts Crystal, Howland Robert H, Wallace Meredith L, Mathew Sanjay J, Price Rebecca B
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Psychiatry, Baylor College of Medicine, Houston, Texas, USA.
Br J Psychiatry. 2025 May 13:1-10. doi: 10.1192/bjp.2024.276.
Understanding the effects of ketamine on depressive symptoms could help identify which patients might benefit and clarify its mechanism of action in both the early (≤1 day post-infusion) and late (e.g. 2-30 days post-infusion) post-infusion periods. Symptom network analyses could provide complementary information regarding relationships between symptoms.
To identify the effects of ketamine on symptom-level changes in depression across both the early and late post-infusion periods and on depressive symptom network changes.
In this secondary analysis of 152 adults with treatment-resistant depression (with 38.8% reporting suicidal ideation at baseline), we compared symptom changes in the early and late post-infusion periods between individuals randomised to a single 40 min infusion of intravenous ketamine 0.5 mg/kg ( = 103) or saline ( = 49) and identified changes in symptom networks between pre- and post-ketamine treatment using network analyses.
In the early post-infusion period, the greatest improvement (comparing ketamine with saline) was in depressive symptoms related to sadness. In network analyses, symptom network connectivity increased following ketamine infusion. Symptoms of sadness and lassitude showed persistent improvement in the first week post-infusion, whereas improvements in suicidal thoughts first emerged 3-4 weeks post-infusion.
Ketamine improved all symptoms but showed the greatest effect on symptoms of sadness, both immediately and in the initial week after treatment. Ketamine also rapidly altered the topology of symptom networks, strengthening interrelationships between residual symptoms. The efficacy of ketamine (compared with saline) regarding suicidal symptoms emerged later. Our findings suggest potentially divergent efficacy, time courses and mechanisms for different symptoms of depression.
了解氯胺酮对抑郁症状的影响有助于确定哪些患者可能从中受益，并阐明其在输注后早期（输注后≤1天）和晚期（如输注后2 - 30天）的作用机制。症状网络分析可以提供有关症状之间关系的补充信息。
确定氯胺酮在输注后早期和晚期对抑郁症状水平变化以及抑郁症状网络变化的影响。
在对152名难治性抑郁症成年人的二次分析中（38.8%的人在基线时报告有自杀意念），我们比较了随机接受单次40分钟静脉输注0.5mg/kg氯胺酮（n = 103）或生理盐水（n = 49）的个体在输注后早期和晚期的症状变化，并使用网络分析确定氯胺酮治疗前后症状网络的变化。
在输注后早期，（氯胺酮与生理盐水相比）改善最明显的是与悲伤相关的抑郁症状。在网络分析中，氯胺酮输注后症状网络的连通性增加。悲伤和倦怠症状在输注后第一周持续改善，而自杀念头的改善在输注后3 - 4周才首次出现。
氯胺酮改善了所有症状，但对悲伤症状的影响在治疗后即刻及最初一周最为显著。氯胺酮还迅速改变了症状网络的拓扑结构，加强了残留症状之间的相互关系。氯胺酮（与生理盐水相比）对自杀症状的疗效出现较晚。我们的研究结果表明，抑郁症不同症状的疗效、时间进程和机制可能存在差异。
