Deuschle M, Schmider J, Weber B, Standhardt H, Körner A, Lammers C H, Schweiger U, Hartmann A, Heuser I
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
J Clin Psychopharmacol. 1997 Jun;17(3):156-60. doi: 10.1097/00004714-199706000-00003.
It has been shown that a single pulse-dosing (PD) dose of clomipramine improves depressive symptoms. However, so far PD and conventional (CONV) application of antidepressants have never been directly compared for an extended period. We performed a double-blind study of PD and CONV application of doxepin (DOX) in depressed patients. After a 1-week placebo treatment, nine parents in the PD group received 250 mg of DOX every 6 days and placebo on the other days until day 39. Ten patients in the CONV group received increasing dosages of DOX until day 7 and 250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)-suppression/corticotropin-releasing hormone (CRH)-stimulation tests were completed: (1)during the initial placebo period; (2)on day 9; and (3)on day 21. In the PD group, scores on the Hamilton Rating Scale for Depression (HAM-D) differed from baseline only after day 36 (17.1 +/- 7.0 vs. 22.7 +/- 2.8, p < 0.03). In the CONV group, however, HAM-D scores improved significantly after 2 days (22.8 +/- 7.2 vs. 26.5 +/- 5.7, p < 0.02) and continued to improve until day 39 (7.3 +/- 5.8). From day 25 to 39, there were significant differences between the HAM-D scores of the two groups. In the PD group, the decline of cortisol after DEX pretreatment was nonsignificant (NS) at both follow-up test occasions (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 micrograms/mL). In the CONV group, a significant decrease was observed at the second test (61.8 +/- 61.9 vs. 10.7 +/- 4.2 vs. 19.8 +/- 19 micrograms/mL, p < 0.05, respectively, NS). The area-under-the-curve cortisol response after CRH was attenuated in the PD group (5,667 +/- 2,910 vs. 1,883 +/- 2,178 vs. 2,239 +/- 2,583 [arbitrary unit], p < 0.01, respectively, p < 0.01) and in the CONV group (5,710 +/- 4,734 vs. 1,267 +/- 2,053 vs. 445 +/- 1,016 [arbitrary unit], NS, respectively, p < 0.02. We conclude that CONV application of DOX is clinically superior compared with PD and that both modes of application have attenuating effects on hypothalamus-pituitary-adrenal system activity.
已表明单脉冲给药（PD）剂量的氯米帕明可改善抑郁症状。然而，到目前为止，抗抑郁药的PD和传统（CONV）应用从未在较长时间内进行过直接比较。我们对抑郁症患者进行了多塞平（DOX）的PD和CONV应用的双盲研究。经过1周的安慰剂治疗后，PD组的9名患者每6天接受250 mg DOX，其他日子接受安慰剂，直至第39天。CONV组的10名患者在第7天之前接受递增剂量的DOX，其他日子接受250 mg DOX，共39天。完成了三项地塞米松（DEX）抑制/促肾上腺皮质激素释放激素（CRH）刺激试验：（1）在初始安慰剂期；（2）在第9天；（3）在第21天。在PD组中，汉密尔顿抑郁量表（HAM-D）评分仅在第36天后与基线有差异（17.1±7.0对22.7±2.8，p<0.03）。然而，在CONV组中，HAM-D评分在2天后显著改善（22.8±7.2对26.5±5.7，p<0.02），并持续改善直至第39天（7.3±5.8）。从第25天到39天，两组的HAM-D评分存在显著差异。在PD组中，DEX预处理后皮质醇的下降在两次随访测试时均无显著意义（NS）（35.9±40.7对24.0±20.7对23.6±26.6微克/毫升）。在CONV组中，在第二次测试时观察到显著下降（61.8±61.9对10.7±4.2对19.8±19微克/毫升，分别为p<0.05，NS）。CRH后皮质醇反应的曲线下面积在PD组中减弱（5,667±2,910对1,883±2,178对2,239±2,583[任意单位]，分别为p<0.01，p<0.01），在CONV组中也减弱（5,710±4,734对1,267±2,053对445±1,016[任意单位]，NS，分别为p<0.02）。我们得出结论，DOX的CONV应用在临床上优于PD，并且两种应用方式对下丘脑-垂体-肾上腺系统活性均有减弱作用。
