Delgado P L, Miller H L, Salomon R M, Licinio J, Krystal J H, Moreno F A, Heninger G R, Charney D S
Department of Psychiatry, West Haven Department of Veterans Affairs Medical Center, Yale University School of Medicine, New Haven, CT, USA.
Biol Psychiatry. 1999 Jul 15;46(2):212-20. doi: 10.1016/s0006-3223(99)00014-1.
Brain serotonin (5-HT) content is dependent on plasma levels of the essential amino acid, tryptophan (TRP). We have previously reported that rapid TRP depletion more frequently reversed the antidepressant response to monoamine oxidase inhibitors and 5-HT reuptake inhibitors than to desipramine (DMI). This study further investigates the relationship of relapse during TRP depletion to antidepressant type in nonrefractory, depressed patients randomly assigned to treatment with either DMI or fluoxetine (FLU).
Fifty-five drug-free depressed (DSM-III-R) patients were randomly assigned to antidepressant treatment with either DMI or FLU. All patients were either treatment naive (n = 34) or had previously received successful antidepressant treatment (n = 21). During the treatment phase, 35 patients had therapeutic responses by predetermined criteria (DMI 18/25; FLU 17/23) and 30 of these (15 DMI responders and 15 FLU responders) went on to TRP depletion testing. Patients received two 2-day test sessions involving administration of similar amino acid drinks. One session led to rapid TRP depletion and the other did not. Behavioral ratings [Hamilton Depression Scale (HDRS)] and plasma for TRP levels were obtained prior to, during, and after testing. Relapse was defined as a 50% increase in HDRS with total < or = 17.
Total and free TRP decreased 70% to 80% 5 hours after the TRP-free drink. While 8/15 FLU responders relapsed, only 1/15 of the DMI responders relapsed. No patient experienced significant depressive symptoms during control testing.
Rapid depletion of plasma TRP transiently reverses the antidepressant response in many patients on FLU but not DMI. Depressive relapse during TRP depletion appears to be more related to antidepressant type than to patient variables since patients were randomly assigned to the two treatments. Antidepressant response to FLU appears to be more dependent on 5-HT availability than that of DMI, suggesting that antidepressants mediate their therapeutic effects through different mechanisms.
脑内5-羟色胺（5-HT）含量取决于必需氨基酸色氨酸（TRP）的血浆水平。我们之前曾报道，与去甲丙咪嗪（DMI）相比，快速色氨酸耗竭更频繁地逆转了单胺氧化酶抑制剂和5-羟色胺再摄取抑制剂的抗抑郁反应。本研究进一步调查了在非难治性抑郁症患者中，色氨酸耗竭期间的复发与抗抑郁药类型之间的关系，这些患者被随机分配接受DMI或氟西汀（FLU）治疗。
55名未服用药物的抑郁症（DSM-III-R）患者被随机分配接受DMI或FLU抗抑郁治疗。所有患者要么是首次接受治疗（n = 34），要么之前接受过成功的抗抑郁治疗（n = 21）。在治疗阶段，35名患者根据预定标准有治疗反应（DMI组18/25；FLU组17/23），其中30名（15名DMI反应者和15名FLU反应者）继续进行色氨酸耗竭测试。患者接受两个为期2天的测试阶段，期间给予类似的氨基酸饮料。一个阶段导致快速色氨酸耗竭，另一个阶段则不会。在测试前、测试期间和测试后获取行为评分[汉密尔顿抑郁量表（HDRS）]和血浆色氨酸水平。复发定义为HDRS增加50%且总分≤17。
饮用不含色氨酸的饮料5小时后，总色氨酸和游离色氨酸下降了70%至80%。15名FLU反应者中有8名复发，而15名DMI反应者中只有1名复发。在对照测试期间，没有患者出现明显的抑郁症状。
血浆色氨酸的快速耗竭在许多服用FLU但未服用DMI的患者中短暂逆转了抗抑郁反应。色氨酸耗竭期间的抑郁复发似乎与抗抑郁药类型的关系比与患者变量的关系更大，因为患者是被随机分配到这两种治疗中的。对FLU的抗抑郁反应似乎比DMI更依赖于5-羟色胺的可用性，这表明抗抑郁药通过不同的机制介导其治疗效果。
