Bowden C L, Brugger A M, Swann A C, Calabrese J R, Janicak P G, Petty F, Dilsaver S C, Davis J M, Rush A J, Small J G
Department of Psychiatry, University of Texas Health Science Center, San Antonio.
JAMA. 1994;271(12):918-24.
To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania.
Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness.
A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals.
After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 mumol/L (150 micrograms/mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively.
Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia.
Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P = .017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P = .004) and 49% for lithium (P = .025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients.
Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.
比较丙戊酸钠与锂盐及安慰剂对急性躁狂症患者的疗效。
对躁郁症患者治疗结果进行的随机、双盲、平行组研究。
共有179名符合躁狂症研究诊断标准的住院急性躁狂患者，其中约一半患者先前对锂盐无反应，在9家大学附属医院进行了研究。
经过至少3天的洗脱期后，按2:1:2的比例随机分配接受丙戊酸钠、锂盐或安慰剂治疗21天。如果耐受，丙戊酸钠和锂盐的剂量分别增加至目标浓度1041微摩尔/升（150微克/毫升）或1.5毫摩尔/升（传统上表示为毫当量/升）。
主要观察指标是源自情感障碍和精神分裂症日程表的躁狂评定量表的变化。
疗效的意向性分析分别基于丙戊酸钠组、锂盐组和安慰剂组68例、35例和73例患者的数据。各组最初具有可比性，但前一年有四次或更多次躁狂发作的所有八名患者均在丙戊酸钠组。在上述组中，分别有30%、33 %和51%的患者因缺乏疗效而提前终止治疗，丙戊酸钠组提前终止治疗的人数少于安慰剂组（P = 0.017）。丙戊酸钠组和锂盐组中症状改善至少50%的患者比例高于安慰剂组：丙戊酸钠组为48%（P = 0.004），锂盐组为49%（P = 0.025），而安慰剂组为25%。丙戊酸钠对快速循环型躁狂患者的疗效与其他患者相同。
丙戊酸钠和锂盐在减轻急性躁狂症状方面均明显比安慰剂有效。丙戊酸钠的疗效似乎与先前对锂盐的反应无关。
