Adams J B, Pyke R E, Costa J, Cutler N R, Schweizer E, Wilcox C S, Wisselink P G, Greiner M, Pierce M W, Pande A C
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, Michigan 48105, USA.
J Clin Psychopharmacol. 1995 Dec;15(6):428-34. doi: 10.1097/00004714-199512000-00007.
This multicenter, double-blind, placebo-controlled, parallel-group, randomized study assessed the efficacy, safety, and tolerability of a novel CCK-B antagonist CI-988 in the treatment of generalized anxiety disorder (GAD). Patients received placebo or CI-988 (300 mg/day, thrice daily) for 4 weeks. Patients with a primary diagnosis of GAD according to DSM-III-R criteria were randomized. The study design included a 1- to 2-week single-blind placebo baseline phase, followed by a 4-week double-blind treatment phase. Efficacy was measured weekly by Hamilton Rating Scale for Anxiety (HAM-A), Clinical Global Impressions of Severity and Change, UCLA-Multi Dimensional Anxiety Scale, and Hamilton Rating Scale for Depression. Patients were also evaluated to determine whether they met criteria for irritable bowel syndrome (IBS) at screening and were evaluated with a gastrointestinal visual analog scale at each visit. Eighty-eight patients were randomized to CI-988 (N = 45) and placebo (N = 43) at three centers. CI-988 did not demonstrate an anxiolytic effect superior to placebo in this clinical trial. There was no significant difference in mean change in HAM-A total between placebo (-7.73) and CI-988 (-8.64). However, a significant treatment-by-center interaction and a highly variable placebo response rate among the three centers limit the interpretation of the results. CI-988 did not have an effect on symptoms of IBS other than diarrhea, which worsened in patients with IBS. Other than a higher incidence of some gastrointestinal symptoms (diarrhea, dyspepsia, flatulence, and nausea), CI-988 was well tolerated. Results suggest that testing higher oral doses of CI-988 may be warranted.
这项多中心、双盲、安慰剂对照、平行组随机研究评估了新型胆囊收缩素B（CCK - B）拮抗剂CI - 988治疗广泛性焦虑症（GAD）的疗效、安全性和耐受性。患者接受安慰剂或CI - 988（300毫克/天，每日三次）治疗4周。根据《精神疾病诊断与统计手册》第三版修订版（DSM - III - R）标准，原发性诊断为GAD的患者被随机分组。研究设计包括1至2周的单盲安慰剂基线期，随后是4周的双盲治疗期。每周通过汉密尔顿焦虑量表（HAM - A）、临床总体印象严重程度和变化量表、加州大学洛杉矶分校多维焦虑量表以及汉密尔顿抑郁量表来测量疗效。患者在筛查时还接受评估以确定是否符合肠易激综合征（IBS）标准，并在每次就诊时使用胃肠道视觉模拟量表进行评估。88名患者在三个中心被随机分为CI - 988组（N = 45）和安慰剂组（N = 43）。在该临床试验中，CI - 988未显示出优于安慰剂的抗焦虑作用。安慰剂组（-7.73）和CI - 988组（-8.64）的HAM - A总分平均变化无显著差异。然而，显著的中心间治疗交互作用以及三个中心间高度可变的安慰剂反应率限制了结果的解读。CI - 988除了对腹泻有影响外，对IBS症状无作用，且IBS患者的腹泻症状加重。除了一些胃肠道症状（腹泻、消化不良、肠胃胀气和恶心）发生率较高外，CI - 988耐受性良好。结果表明可能有必要测试更高口服剂量的CI - 988。
