Ketamine metabolite pilot study in a suicidal depression trial
Ketamine metabolite pilot study in a suicidal depression trial
复制标题
DOI：
10.1016/j.jpsychires.2019.08.005
复制
发表时间：
2019-10-01
影响因子：
4.8
通讯作者：
Mann, J. John
中科院分区：
文献类型：
--
作者：
Grunebaum, Michael F.;Galfalvy, Hanga C.;Mann, J. John
氯胺酮有望成为治疗抑郁症和自杀意念的速效疗法，但副作用和滥用的可能性限制了其使用。了解其作用机制有助于开发类似但更安全的药物。这项事后研究探讨了氯胺酮和代谢物（包括羟基去甲氯胺酮对映体、(2S,6S)-和(2R,6R)-HNK）与已发表的自杀性抑郁症试验亚组临床反应的关系。具有临床显着自杀意念的抑郁成人被随机分配接受亚麻醉氯胺酮或咪达唑仑双盲输注。输注后测量氯胺酮和代谢物（N = 53）。血浆 (2R,6R)-HNK 与从基线到输注后 24 小时的抑郁症变化（较高水平与较少的临床改善相关）（HDRS-24：Spearman r = 0.37，p = 0.009）和自杀想法（SSI：Spearman r = 0.29，p = 0.041）相关。 HNK 对映体和去氢去甲氯胺酮 (DHNK) 与每周随访临床评分存在相似的相关性。氯胺酮和去甲氯胺酮与抑郁或自杀意念的变化无关（未经调整 p > 0.28）。
Ketamine shows promise as a rapidly-acting treatment for depression and suicidal ideation, but side effects and abuse potential limit its use. Understanding its mechanism of action could help develop analogous but safer drugs. This post hoc study explored relationships of ketamine and metabolites, including hydroxynorketamine enantiomers, (2S,6S)- and (2R,6R)-HNK, to clinical response in a subgroup from a published trial in suicidal depression. Depressed adults with clinically significant suicidal ideation were randomized to double-blind infusion of sub-anesthetic ketamine or midazolam. Ketamine and metabolites were measured after infusion (N = 53). Plasma (2R,6R)-HNK was associated with change (higher levels correlated with less clinical improvement) from baseline to 24 h post-infusion of depression (HDRS-24: Spearman r = 0.37, p = 0.009) and suicidal thoughts (SSI: Spearman r = 0.29, p = 0.041). There were similar correlations with weekly follow-up clinical rating scores for both HNK enantiomers and dehydronorketamine (DHNK). Ketamine and norketamine were not associated with change in depression or suicidal ideation (unadjusted p > 0.28).