Burke W J, McArthur-Miller D A
University of Nebraska Medical Center, Department of Psychiatry, Omaha 68198-5580, USA.
J Clin Psychiatry. 2001;62 Suppl 22:38-42.
Antidepressant medications are typically taken on a daily basis owing to both tradition and the pharmacokinetics of these agents. Because fluoxetine and its primary metabolite norfluoxetine have long half-lives and flat dose-response curves, we examined the tolerability of a weekly dose and its equivalence to daily dosing during the continuation phase of treatment for major depressive disorder (MDD). Open-label treatment with 20 mg of fluoxetine daily for 7 weeks began with 114 subjects. Subsequently, 70 subjects who met criteria for response were randomly assigned in a double-blind design to 1 of 3 treatment groups (20 mg of fluoxetine daily [N = 21], 60 mg of fluoxetine weekly [N = 28], or placebo [N = 21]) and followed for 7 weeks. No statistically significant differences were observed in several clinical measures. Tolerability in the 3 groups was similar; there was no difference in dropout rates or adverse events. Hence, weekly dosing of fluoxetine appears to be well tolerated and possibly as effective as daily dosing in the treatment of MDD. It is proposed that less frequent dosing could potentially benefit patients by enhancing adherence and minimizing the risk of side effects and drug-drug interactions.
由于传统以及这些药物的药代动力学特性，抗抑郁药物通常需要每日服用。因为氟西汀及其主要代谢产物去甲氟西汀具有较长的半衰期和平坦的剂量反应曲线，我们研究了每周一次给药的耐受性及其在重度抑郁症（MDD）治疗延续阶段与每日给药的等效性。114名受试者开始接受为期7周的每日20毫克氟西汀的开放标签治疗。随后，70名符合反应标准的受试者被随机分配到3个治疗组中的1组（每日20毫克氟西汀 [N = 21]、每周60毫克氟西汀 [N = 28] 或安慰剂 [N = 21]），并随访7周。在多项临床指标上未观察到统计学上的显著差异。3组的耐受性相似；脱落率或不良事件方面没有差异。因此，在MDD治疗中，氟西汀每周给药似乎耐受性良好，且可能与每日给药一样有效。有人提出，减少给药频率可能通过提高依从性以及将副作用和药物相互作用的风险降至最低而使患者受益。
