Rapaport Mark Hyman, Schneider Lon S, Dunner David L, Davies John T, Pitts Cornelius D
Department of Psychiatry, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, 8730 Alden Dr., Suite C301, Los Angeles, CA 90048, USA.
J Clin Psychiatry. 2003 Sep;64(9):1065-74. doi: 10.4088/jcp.v64n0912.
Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition.
In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score.
The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo.
Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.
抑郁症是美国老年人中第二常见的神经精神疾病，会产生巨大的临床和公共卫生成本。尽管治疗方法有所进步，但老年期抑郁症仍是一项临床挑战。虽然选择性5-羟色胺再摄取抑制剂（SSRI）是治疗老年期抑郁症最常用的药物干预手段，但很少有安慰剂对照试验评估SSRI对这种疾病的疗效。
在这项为期12周的多中心、安慰剂对照、灵活剂量、双盲、随机试验中，319名老年患者（平均年龄 = 70岁）接受了每日最高剂量50毫克的缓释帕罗西汀（N = 104）、每日最高剂量40毫克的速释帕罗西汀（N = 106）或安慰剂（N = 109）治疗。患者符合《精神疾病诊断与统计手册》第四版（DSM-IV）中重度抑郁症的标准，且在17项汉密尔顿抑郁量表（HAM-D）上的总分达到18分或更高。主要疗效指标是HAM-D总分从基线到终点的变化。
主要疗效分析显示，在第12周末次观察结转（LOCF）终点时，缓释帕罗西汀与安慰剂相比，HAM-D评分从基线的变化的校正差异为-2.6（95%置信区间[CI] = -4.47至-0.73，p = 0.007）。在第12周时，速释帕罗西汀与安慰剂的校正差异为-2.8（95% CI = -4.65至-0.99，p = 0.003）。缓释帕罗西汀和速释帕罗西汀比安慰剂更有效，活性治疗组的平均±标准差终点HAM-D总分分别为10.0±7.41和10.0±7.10，而安慰剂组为12.6±7.34。在临床总体印象-总体改善量表上得分为1或2被定义为有反应，缓释帕罗西汀组72%的患者达到该标准（LOCF；与安慰剂相比p < 0.002），速释帕罗西汀组65%的患者达到该标准（与安慰剂相比p = 0.06），安慰剂组52%的患者达到该标准。HAM-D总分≤7被定义为缓解，缓释帕罗西汀组43%的患者达到该标准（LOCF；与安慰剂相比p = 0.009），速释帕罗西汀组44%的患者达到该标准（与安慰剂相比p = 0.01），安慰剂组26%的患者达到该标准。在一项事后分析中，缓释帕罗西汀和速释帕罗西汀在HAM-D上的平均改善程度在慢性抑郁症患者（病程>2年）和短期（≤2年）抑郁症患者中均大于安慰剂。因不良事件导致的脱落率，缓释帕罗西汀组为12.5%，速释帕罗西汀组为16.0%，安慰剂组为8.3%。
缓释帕罗西汀和速释帕罗西汀是治疗老年患者重度抑郁症（包括慢性抑郁症患者）的有效且耐受性良好的治疗方法。
