Smith Mark A, McCoy Robin, Hamer-Maansson Jennifer, Brecher Martin
AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, PO Box 15437, Wilmington, DE 19850, USA.
J Clin Psychopharmacol. 2005 Aug;25(4):331-5. doi: 10.1097/01.jcp.0000168486.14516.7c.
The original dosing recommendations for quetiapine in the treatment of schizophrenia suggested escalation to 400 mg/d using the following schedule, administered twice daily in divided doses: Day 1, 50 mg; Day 2, 100 mg; Day 3, 200 mg; Day 4, 300 mg; Day 5, 400 mg. In practice, however, clinicians often exceed these recommendations because of the need to obtain a therapeutic response in patients with psychosis as quickly as possible. This study was designed to determine a faster tolerable dosage-escalation schedule for quetiapine in acutely ill, hospitalized patients with schizophrenia. In this multicenter, placebo-controlled, double-blind pilot study, adult patients were randomly assigned to escalation schedules that would achieve a target dosage of 400 mg/d in either 5, 3, or 2 days. Safety and tolerability were assessed by interviews, physical examinations and vital signs, laboratory tests, and electrocardiograms. The enrolled population consisted of 69 patients who were randomized to 1 of the 3 dose-escalation schedules. Treatment-related adverse events were few among the 67 evaluable patients, with most rated as mild in intensity. Among 69 enrolled patients, only 3 withdrew because of an adverse event (agitation). Objective assessments and adverse events were similar between the 3 groups. In this study of patients with acute schizophrenia, quetiapine dosage was increased to 400 mg/d in 5, 3, and 2 days with similar safety and tolerability, suggesting that escalation to therapeutically effective dosages can be accomplished in less than 5 days.
喹硫平治疗精神分裂症的初始剂量建议为采用以下给药方案逐渐增至400mg/天,分两次给药:第1天,50mg;第2天,100mg;第3天,200mg;第4天,300mg;第5天,400mg。然而在实际应用中,由于需要尽快使精神病患者获得治疗反应,临床医生常常超过这些建议剂量。本研究旨在确定一种更快的、能为急性发病且住院的精神分裂症患者耐受的喹硫平剂量递增方案。在这项多中心、安慰剂对照、双盲的初步研究中,成年患者被随机分配至不同的递增方案,这些方案可在5天、3天或2天内达到400mg/天的目标剂量。通过访谈、体格检查和生命体征、实验室检查以及心电图评估安全性和耐受性。纳入人群包括69名患者,他们被随机分配至3种剂量递增方案中的一种。在67名可评估患者中,与治疗相关的不良事件较少,大多数不良事件强度被评为轻度。在69名纳入患者中,仅有3名因不良事件(激越)退出研究。3组之间的客观评估和不良事件相似。在这项针对急性精神分裂症患者的研究中,喹硫平剂量可在5天、3天和2天内增至400mg/天,安全性和耐受性相似,这表明可在不到5天的时间内增至治疗有效剂量。