(R,S)-ketamine (ketamine) and its enantiomer (S)-ketamine (esketamine) can produce rapid and substantial antidepressant effects. However, individual response to ketamine/esketamine is variable, and there are no well-accepted methods to differentiate persons who are more likely to benefit. Numerous potential peripheral biomarkers have been reported, but their current utility is unclear. We conducted a systematic review/meta-analysis examining the association between baseline levels and longitudinal changes in blood-based biomarkers, and response to ketamine/esketamine. Of the 5611 citations identified, 56 manuscripts were included (N = 2801 participants), and 26 were compatible with meta-analytical calculations. Random-effect models were used, and effect sizes were reported as standardized mean differences (SMD). Our assessments revealed that more than 460 individual biomarkers were examined. Frequently studied groups included neurotrophic factors (n = 15), levels of ketamine and ketamine metabolites (n = 13), and inflammatory markers (n = 12). There were no consistent associations between baseline levels of blood-based biomarkers, and response to ketamine. However, in a longitudinal analysis, ketamine responders had statistically significant increases in brain-derived neurotrophic factor (BDNF) when compared to pre-treatment levels (SMD [95% CI] = 0.26 [0.03, 0.48], p = 0.02), whereas non-responders showed no significant changes in BDNF levels (SMD [95% CI] = 0.05 [−0.19, 0.28], p = 0.70). There was no consistent evidence to support any additional longitudinal biomarkers. Findings were inconclusive for esketamine due to the small number of studies (n = 2). Despite a diverse and substantial literature, there is limited evidence that blood-based biomarkers are associated with response to ketamine, and no current evidence of clinical utility.

( R,S )-氯胺酮(ketamine)及其对映体( S )-氯胺酮(esketamine)可产生快速而显着的抗抑郁作用。然而，个体对氯胺酮/艾氯胺酮的反应各不相同，并且没有公认的方法来区分更有可能受益的人。已经报道了许多潜在的外周生物标志物，但它们目前的用途尚不清楚。我们进行了一项系统回顾/荟萃分析，检查基线水平与基于血液的生物标志物的纵向变化之间的关联，以及对氯胺酮/艾氯胺酮的反应。在确定的 5611 篇引文中，包含了 56 篇手稿（N = 2801 名参与者），26 名参与者符合元分析计算。使用随机效应模型，效应大小报告为标准化均值差 (SMD)。我们的评估显示，检查了超过 460 个单独的生物标志物。经常研究的组包括神经营养因子 ( n  = 15)、氯胺酮和氯胺酮代谢物水平 ( n  = 13) 和炎症标志物 ( n  = 12)。基于血液的生物标志物的基线水平与对氯胺酮的反应之间没有一致的关联。然而，在纵向分析表明，与治疗前水平相比，氯胺酮反应者的脑源性神经营养因子 (BDNF) 在统计学上显着增加（SMD [95% CI] = 0.26 [0.03, 0.48]，p = 0.02），而无反应者则 没有BDNF 水平的显着变化（SMD [95% CI] = 0.05 [−0.19, 0.28]，p  = 0.70）。没有一致的证据支持任何额外的纵向生物标志物。由于研究数量较少 ( n  = 2)，艾氯胺酮的研究结果尚无定论。尽管有多种多样的大量文献，但只有有限的证据表明基于血液的生物标志物与对氯胺酮的反应有关，并且目前没有临床实用性的证据。