Sheehan David V, Sheehan Kathy Harnett, Raj B A
Department of Psychiatry, University of South Florida College of Medicine, Tampa, Florida 33613, USA.
Psychopharmacol Bull. 2007;40(2):63-81.
This study compares the speed of onset of action of the extended release (XR) formulation of alprazolam with that of the compressed tablet (CT) formulation in a sample of outpatients with DSM-IV panic disorder. Diary records of hourly antianxiety benefit from a 9-week open label switch study of 30-patients stabilized on alprazolam- CT for 3 weeks and then switched to an equivalent dose of alprazolam-XR, were used to examine the timing and magnitude of clinical benefit on both formulations. The magnitude of benefit at the first hour after the first morning dose was similar for both formulations. The peak benefit, over the hours after the first morning dose, was also similar and 90% of peak benefit that was achieved in the first hour on both formulations. Mean time to peak benefit was similar (1.5 h for alprazolam-CT vs. 1.6 h for alprazolam-XR) and the percent of patients achieving peak benefit in the first hour was also similar. Compared to the CT formulation, alprazolam-XR had a much longer duration of therapeutic action (11.3 +/- 4.2 h vs. 5.1 +/- 1.7 h). The results, which may be related to the biotechnology (and resultant pharmacokinetic profile) of the XR preparation, suggest that alprazolam-XR has value as a "rescue" as well as a prophylactic or maintenance treatment in panic disorder. These results must be viewed in the context of the study limitations including its small size, the lack of independence of groups in a switch study, and the limitations of the diary records used.
本研究比较了阿普唑仑缓释(XR)制剂与普通片剂(CT)制剂在患有DSM-IV惊恐障碍的门诊患者样本中的起效速度。通过对30名患者进行的为期9周的开放标签转换研究的日记记录来检查两种制剂临床获益的时间和程度,这些患者先用阿普唑仑CT稳定治疗3周,然后转换为等效剂量的阿普唑仑XR,记录每小时抗焦虑获益情况。两种制剂在第一天早晨服药后第一小时的获益程度相似。第一天早晨服药后的数小时内,两种制剂的获益峰值也相似,且均达到第一小时获益峰值的90%。达到获益峰值的平均时间相似(阿普唑仑CT为1.5小时,阿普唑仑XR为1.6小时),且在第一小时达到获益峰值的患者百分比也相似。与CT制剂相比,阿普唑仑XR的治疗作用持续时间长得多(分别为11.3±4.2小时和5.1±1.7小时)。这些结果可能与XR制剂的生物技术(以及由此产生的药代动力学特征)有关,表明阿普唑仑XR在惊恐障碍中作为“急救”以及预防性或维持性治疗均有价值。这些结果必须结合研究局限性来看待,包括样本量小、转换研究中组间缺乏独立性以及所使用日记记录的局限性。