A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania.
A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania.
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DOI：
10.1007/s00213-020-05654-1
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发表时间：
2020-12
影响因子：
3.4
通讯作者：
Cowen PJ
中科院分区：
文献类型：
--
作者：
Sharpley AL;Williams C;Holder AA;Godlewska BR;Singh N;Shanyinde M;MacDonald O;Cowen PJ
锂是双相情感障碍的有效预防和抗躁狂治疗;然而，由于耐受性差和毒性，其使用正在下降。锂抑制肌醇单磷酸酶（IMPase），这是一种可能的关键治疗机制。抗炎药ebselen也能抑制IMPase，并且耐受性良好且安全。使用Young躁狂量表（YMRS）（主要结局）和Altman躁狂自评量表（ASRM）量表和临床总体印象-严重程度量表（CGI-S）评估辅助依布selen治疗躁狂症的疗效。随机、双盲、安慰剂对照、平行组试验，于2017年10月至2019年6月在Oxford Health NHS Foundation Trust进行。药物对照随机化是计算机生成的，完全隐藏分配。年龄在18-70岁之间，经历躁狂或轻躁狂的住院/门诊患者（n = 68）被分配到3周的依布硒啉（600 mg bd）（n = 33）或安慰剂（n = 35）。参与者接受常规临床护理和精神药物治疗。依布硒仑在降低YMRS（校正的平均差异和95%置信区间，-1.71（-5.34至1.91），p = 0.35）和ASRM（-1.36（-3.75至1.17），p = 0.29）评分方面在数值上优于安慰剂，但在统计学上没有优势。然而，依布硒治疗的参与者在第3周的CGI-S评分显著较低（调整后的平均差异为-0.58（-1.14至-0.03），p = 0.04）。排除接受丙戊酸盐伴随治疗的患者的事后分析放大了依布硒啉与安慰剂之间在YMRS上的差异。两组之间的不良事件相当，并且轻微。Ebselen值得进一步研究，其中合并精神药物控制更好，排除了服用丙戊酸盐的受试者。如果有效的话，依布硒啉的上级耐受性和安全性将使其成为锂的有用替代品。试验登记处：www.clinicaltrials.gov，标识符：NCT 03013400。本文的在线版本（10.1007/s 00213 -020-05654-1）包含补充材料，可供授权用户使用。
Lithium is an effective prophylactic and anti-manic treatment in bipolar disorder; however, its use is declining through perceived poor tolerance and toxicity. Lithium inhibits inositol monophosphatase (IMPase), a probable key therapeutic mechanism. The anti-inflammatory drug, ebselen, also inhibits IMPase and appears well-tolerated and safe. To assess the efficacy of adjunctive ebselen in mania using the Young Mania Rating Scale (YMRS) (primary outcome) and the Altman Self-Rating Mania (ASRM) Scale and Clinical Global Impression-Severity Scale (CGI-S) among the secondary outcomes. Randomised, double-blind, placebo-controlled, parallel-group trial conducted between October 2017 and June 2019, at Oxford Health NHS Foundation Trust. Pharmacy-controlled randomisation was computer-generated, with full allocation concealment. In/outpatients (n = 68) aged 18–70, experiencing mania or hypomania, were assigned to 3 weeks ebselen (600 mg bd) (n = 33) or placebo (n = 35). Participants received usual clinical care and psychotropic medication. Ebselen was numerically, but not statistically, superior to placebo in lowering scores on the YMRS (adjusted mean difference and 95% confidence interval, − 1.71 (− 5.34 to 1.91), p = 0.35) and ASRM (− 1.36 (− 3.75 to 1.17), p = 0.29). However, scores on the CGI-S were significantly lower at week 3 in ebselen-treated participants (adjusted mean difference, − 0.58 (− 1.14 to − 0.03), p = 0.04). A post hoc analysis excluding patients taking concomitant valproate treatment magnified the difference between ebselen and placebo on the YMRS. Adverse events were comparable between groups, and mild. Ebselen merits further investigation where concomitant psychotropic medication is better controlled and participants taking valproate are excluded. If effective, ebselen’s superior tolerance and safety could make it a useful alternative to lithium. Trial Registry: www.clinicaltrials.gov, Identifier: NCT03013400. The online version of this article (10.1007/s00213-020-05654-1) contains supplementary material, which is available to authorized users.
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影响因子：
17.7
作者：
Keck, PE;Marcus, R;Ingenito, G
通讯作者：
Ingenito, G
影响因子：
3.4
作者：
Masaki C;Sharpley AL;Cooper CM;Godlewska BR;Singh N;Vasudevan SR;Harmer CJ;Churchill GC;Sharp T;Rogers RD;Cowen PJ
通讯作者：
Cowen PJ
影响因子：
10.6
作者：
Altman, EG;Hedeker, D;Davis, JM
通讯作者：
Davis, JM
影响因子：
10.6
作者：
Rush, AJ;Trivedi, MH;Keller, MB
通讯作者：
Keller, MB
DOI：
10.1038/npp.2015.343
发表时间：
2016-06
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Singh N;Sharpley AL;Emir UE;Masaki C;Herzallah MM;Gluck MA;Sharp T;Harmer CJ;Vasudevan SR;Cowen PJ;Churchill GC
通讯作者：
Churchill GC