Price L H, Charney D S, Delgado P L, Heninger G R
Clinical Neuroscience Research Unit, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven 06508.
J Clin Psychopharmacol. 1990 Oct;10(5):312-7.
The clinical efficacy of lithium augmentation in refractory depression is hypothesized to depend on the ability of lithium to enhance presynaptic 5-hydroxytryptamine (5-HT) function. Since fenfluramine promotes release and inhibits reuptake of presynaptic 5-HT, we assessed its efficacy in augmenting ongoing tricyclic antidepressant treatment of refractory depression. Fifteen patients with DSM-III major depression failed to respond to treatment with desipramine 2.5 mg/kg/day or more (plasma levels of at least 125 ng/ml) given for at least 4 weeks. Fenfluramine 40-120 mg/day was then added to the ongoing desipramine in a placebo substitution design. There was no statistically significant evidence of either transient or sustained clinical improvement during the 2 weeks of fenfluramine augmentation. One patient appeared to respond to the treatment, but one appeared to worsen. Fenfluramine more than doubled steady-state plasma levels of desipramine. These findings suggest that lithium's efficacy as an augmenting agent depends on properties that are not shared by fenfluramine. Fenfluramine cannot be recommended in the routine management of refractory depression.
锂盐增效治疗难治性抑郁症的临床疗效据推测取决于锂盐增强突触前5-羟色胺（5-HT）功能的能力。由于芬氟拉明可促进突触前5-HT的释放并抑制其再摄取，我们评估了其在增强三环类抗抑郁药对难治性抑郁症的持续治疗效果方面的功效。15例符合《精神疾病诊断与统计手册》第三版（DSM-III）标准的重度抑郁症患者，在接受至少4周的地昔帕明治疗（剂量为2.5mg/kg/天或更高，血浆水平至少为125ng/ml）后无效。然后采用安慰剂替代设计，在持续的地昔帕明治疗中添加40 - 120mg/天的芬氟拉明。在芬氟拉明增效治疗的2周内，没有统计学上显著的证据表明有短暂或持续的临床改善。1例患者似乎对治疗有反应，但1例似乎病情恶化。芬氟拉明使地昔帕明的稳态血浆水平增加了一倍多。这些发现表明，锂盐作为增效剂的疗效取决于芬氟拉明所不具备的特性。在难治性抑郁症的常规治疗中，不推荐使用芬氟拉明。
