International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.
International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.
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DOI：
10.1038/s41380-022-01757-7
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发表时间：
2022-12
影响因子：
11
通讯作者：
Wallace, Meredith L.
中科院分区：
文献类型：
--
作者：
Price, Rebecca B.;Kissel, Nicholas;Baumeister, Andrew;Rohac, Rebecca;Woody, Mary L.;Ballard, Elizabeth D.;Zarate, Carlos A., Jr.;Deakin, William;Abdallah, Chadi G.;Feder, Adriana;Charney, Dennis S.;Grunebaum, Michael F.;Mann, J. John;Mathew, Sanjay J.;Gallagher, Bronagh;McLoughlin, Declan M.;Murrough, James W.;Muthukumaraswamy, Suresh;McMillan, Rebecca;Sumner, Rachael;Papakostas, George;Fava, Maurizio;Hock, Rebecca;Phillips, Jennifer L.;Blier, Pierre;Shiroma, Paulo;Sos, Peter;Su, Tung-Ping;Chen, Mu-Hong;Tiger, Mikael;Lundberg, Johan;Wilkinson, Samuel T.;Wallace, Meredith L.
抑郁症是致残的，而且非常普遍。静脉（IV）氯胺酮显示出快速起效的抗抑郁特性，但对于哪些患者最有可能受益知之甚少，这限制了个性化处方。我们确定了IV氯胺酮的随机对照试验，这些试验招募了具有相关精神诊断的个体(例如，单极或双相抑郁症；创伤后应激障碍)，包括一个或多个对照组，没有提供任何其他与氯胺酮联合的研究管理治疗（尽管临床规定的同时治疗是允许的），并使用Montgomery-Åsberg抑郁评定量表或汉密尔顿抑郁评定量表（HRSD-17）评估结果。25项符合条件的试验中有17项获得了至少一项结果的个体患者水平数据[汇总n = 809]。从这17项研究中征集的33个调节因子的参与者级数据可用率从10.8%到100%不等（中位数= 55.6%）。在数据协调之后，对至少40%的数据集中可用的版主进行了顺序测试，并使用数据驱动的组合版主方法进行了测试。氯胺酮对急性[~24小时]的主要作用β*(95% ci) = 0.58 (0.44, 0.72)；P < 0.0001]和急性后[~7天]；β*(95% ci) = 0.38 (0.23, 0.54)；P < 0.0001]。两项研究水平的调节因子被认为是显著的：氯胺酮效应（相对于安慰剂）在研究开始时需要对联邦监管机构批准的抗抑郁药物有较高程度的治疗耐药性（≥2项失败的试验）的研究中更大；在使用交叉设计的研究中。对联合调节因子进行全面的数据驱动搜索，确定了具有统计学意义但适度且临床信息不足的效应（效应大小r≤0.29，为中小型效应）。氯胺酮在不同类型的患者中均能有效减轻抑郁症状，在对既往药物更耐药的患者中，其益处甚至比安慰剂更大。在迄今为止将精准医学方法应用于氯胺酮治疗的最大努力中，没有发现可用于指导氯胺酮治疗决策的临床或人口统计学患者水平特征。审核注册：PROSPERO标识符：CRD42021235630
Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; β*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions. Review Registration: PROSPERO Identifier: CRD42021235630
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影响因子：
11
作者：
Fava M;Freeman MP;Flynn M;Judge H;Hoeppner BB;Cusin C;Ionescu DF;Mathew SJ;Chang LC;Iosifescu DV;Murrough J;Debattista C;Schatzberg AF;Trivedi MH;Jha MK;Sanacora G;Wilkinson ST;Papakostas GI
通讯作者：
Papakostas GI
影响因子：
4.2
作者：
Matveychuk, Dmitriy;Thomas, Rejish K.;Dursun, Serdar M.
通讯作者：
Dursun, Serdar M.
影响因子：
17.7
作者：
Dwyer, Jennifer B.;Landeros-Weisenberger, Angeli;Bloch, Michael H.
通讯作者：
Bloch, Michael H.
影响因子：
10.6
作者：
Berman, RM;Cappiello, A;Krystal, JH
通讯作者：
Krystal, JH
影响因子：
4.4
作者：
Chen, Mu -Hong;Kao, Chung-Feng;Su, Tung-Ping
通讯作者：
Su, Tung-Ping