Stauffer Virginia L, Baygani Simin K, Kinon Bruce J, Krikke-Workel Judith O
From the *Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN; and †Eli Lilly Nederland, Houten, The Netherlands.
J Clin Psychopharmacol. 2014 Oct;34(5):552-8. doi: 10.1097/JCP.0000000000000187.
This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial.
这项为期6周的多中心随机撤药、安慰剂对照试验旨在确定精神分裂症患者突然停用代谢型谷氨酸2/3受体激动剂聚谷氨酸甲硫氨酸（LY2140023一水合物）后是否会出现身体依赖症状。符合条件的18至65岁门诊患者，若需要调整或开始使用抗精神病药物，在开放标签治疗期间接受4周的聚谷氨酸甲硫氨酸治疗，然后随机、双盲地继续使用聚谷氨酸甲硫氨酸或接受2周的安慰剂治疗。主要结局比较了在随机撤药阶段，聚谷氨酸甲硫氨酸治疗组与安慰剂组患者在停用症状清单-改良里克尔斯量表上总分的3天移动平均值结果。每天使用电子患者报告结局（ePRO）设备记录这些结果。在撤药阶段，103名患者被随机分组，98名患者完成了试验。根据停用症状清单-改良里克尔斯量表测量，与继续使用聚谷氨酸甲硫氨酸相比，没有统计学上显著的证据表明安慰剂会导致撤药症状（P = 0.170）。临床医生评定的酒精戒断临床研究所修订评估量表的二次分析结果支持了上述结果，该分析显示治疗组之间没有统计学上的显著差异。使用ePRO设备，82.5%的患者依从性达到75%至100%。在研究的任何阶段，均未报告因精神分裂症恶化、严重不良事件、死亡或癫痫发作而停药的情况。这些发现表明，没有证据表明突然停用聚谷氨酸甲硫氨酸会出现撤药症状，并且ePRO设备可以成功用于多中心精神分裂症试验。
