Moore P, Gillin C, Bhatti T, DeModena A, Seifritz E, Clark C, Stahl S, Rapaport M, Kelsoe J
Department of Psychiatry, University of California, San Diego Mental Health Clinical Research Center, VA San Diego Health Care System, 92161, USA.
Arch Gen Psychiatry. 1998 Jun;55(6):534-9. doi: 10.1001/archpsyc.55.6.534.
In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs.
Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram.
The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree.
Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients, however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.
在先前的研究中,通过给予无色氨酸氨基酸饮料(TFD)来耗尽大脑中的血清素,(1)可暂时逆转有重度抑郁症病史的心境正常患者中选择性血清素再摄取抑制剂(SSRI)的抗抑郁作用,且(2)可增加正常志愿者的快速眼动(REM)睡眠。在本研究中,我们假设TFD不仅会增加使用SSRI治疗的心境正常患者的抑郁症状,还会增加其REM睡眠倾向。
10名有重度抑郁发作病史且病情完全缓解、正在接受药物治疗的男性患者,在不同日期以双盲、随机顺序摄入100克TFD(实验剂量)或25克TFD(设计为对照饮料)。通过情绪评分、血浆色氨酸浓度和整夜睡眠脑电图来评估其效果。
TFD导致血浆色氨酸浓度、睡眠潜伏期和REM潜伏期呈剂量依赖性降低,同时REM百分比、REM时长、REM密度和总睡眠时间增加。两种剂量的TFD均未使情绪发生具有临床意义的改变。
尽管TFD影响了血浆色氨酸浓度和各种睡眠指标,但我们的研究并未证实先前的报道,即TFD会暂时逆转心境正常患者中SSRI的抗抑郁作用。然而,我们的患者接受SSRI治疗的时间更长,且在研究时病情缓解更完全。我们的结果表明,在接受SSRI治疗且病情缓解的患者中,TFD诱发的病情复发会随着治疗持续时间、缓解程度或两者的作用而降低。