Rickels Karl, Mathew Sanjay, Banov Michael D, Zimbroff Daniel L, Oshana Scott, Parsons Edward C, Donahue Stephen R, Kauffman Michael, Iyer Ganesh R, Reinhard John F
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
J Clin Psychopharmacol. 2008 Apr;28(2):235-9. doi: 10.1097/JCP.0b013e31816774de.
PRX-00023, a serotonin 1A receptor agonist, was designed to provide high potency and selectivity for its target. To assess the possible therapeutic utility in anxiety, a randomized, double-blind, placebo-controlled trial was conducted in 311 subjects who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for generalized anxiety disorder. All subjects underwent a 1-week placebo run-in and were randomized to receive once-daily capsules containing either PRX-00023 (80 mg/d) or placebo for an additional 8 weeks. The primary outcome measure was the Hamilton Anxiety Scale (HAM-A). The Montgomery-Asberg Depression Rating Scale was used as a secondary endpoint to measure depressive symptoms. Statistical testing was performed with analysis of covariance, between baseline and week 8, with baseline values as a covariate. The anxiolytic effect of PRX-00023, compared with placebo, showed trends across all anxiolytic measures but failed to reach significance on the primary endpoint (HAM-A total score). Among the components of the HAM-A total score, the anxious mood item was significantly different from placebo in the PRX-00023-treated group (-1.015 vs -0.748; P = 0.02). The scores of the Montgomery-Asberg Depression Rating Scale were significantly improved compared with placebo at week 8 (-4.5 vs -1.6; P = 0.0094 in the last observation carried forward analysis). PRX-00023 was well tolerated; of note, there were no drug-related serious adverse events, and more patients discontinued due to adverse events in the placebo group (2.9%) than in the PRX-00023 group (1.4%). The most common adverse event was headache, observed in 15.7% and 10.9% of PRX-00023- and placebo-treated patients, respectively. Furthermore, there was no evidence of impaired sexual function, as measured by the Massachusetts General Hospital Sexual Function Scale. Collectively, these results support further clinical investigation of higher doses of PRX-00023 in anxiety and depression.
PRX - 00023是一种5-羟色胺1A受体激动剂，其设计目的是对其靶点具有高效能和选择性。为评估其在焦虑症方面可能的治疗效用，对311名符合《精神疾病诊断与统计手册》第四版广泛性焦虑症标准的受试者进行了一项随机、双盲、安慰剂对照试验。所有受试者都经历了为期1周的安慰剂导入期，然后被随机分配接受每日一次的胶囊，其中要么含有PRX - 00023（80毫克/天），要么含有安慰剂，持续另外8周。主要结局指标是汉密尔顿焦虑量表（HAM - A）。蒙哥马利 - 阿斯伯格抑郁评定量表用作测量抑郁症状的次要终点。采用协方差分析进行统计检验，在基线和第8周之间，以基线值作为协变量。与安慰剂相比，PRX - 00023的抗焦虑作用在所有抗焦虑测量指标上都呈现出趋势，但在主要终点（HAM - A总分）上未达到显著水平。在HAM - A总分的各个组成部分中，PRX - 00023治疗组的焦虑情绪项目与安慰剂有显著差异（-1.015对 - 0.748；P = 0.02）。在第8周时，蒙哥马利 - 阿斯伯格抑郁评定量表的得分与安慰剂相比有显著改善（-4.5对 - 1.6；末次观察结转分析中P = 0.0094）。PRX - 00023耐受性良好；值得注意的是，没有与药物相关的严重不良事件，并且因不良事件而停药的患者在安慰剂组（2.9%）比在PRX - 00023组（1.4%）更多。最常见的不良事件是头痛，分别在接受PRX - 00023和安慰剂治疗的患者中观察到15.7%和10.9%。此外，根据麻省总医院性功能量表测量，没有性功能受损的证据。总体而言，这些结果支持对更高剂量的PRX - 00023在焦虑症和抑郁症方面进行进一步的临床研究。
