Salomon R M, Miller H L, Delgado P L, Charney D
Psychiatry Department, Yale University School of Medicine, VA Medical Center, West Haven, CT 06516.
Int Clin Psychopharmacol. 1993 Nov;8 Suppl 2:41-6. doi: 10.1097/00004850-199311002-00006.
The results from these and other studies provide an opportunity to critically re-examine the role of brain monoamine function in the pathophysiology of depression and the mechanism of action of antidepressant drugs. The following observations are most salient: 1. Tryptophan depletion, which reduces brain serotonin function, reverses the therapeutic effects of specific serotonin reuptake inhibitors (SSRIs) but not drugs which potently inhibit noradrenaline reuptake. In contrast, depletion of noradrenaline and dopamine, as a consequence of AMPT administration, reverses the remission induced by noradrenaline (desipramine) and dopamine (mazindol) reuptake inhibitors, but not SSRIs. These data suggest that the efficacy of antidepressant drugs may not be due to a common mechanism involving a single monoamine system. SSRIs and noradrenaline reuptake inhibitors may work via primary actions on serotonin and noradrenaline function, respectively. Alternatively, these two classes of antidepressant drugs may exert their therapeutic properties by affecting the function of an, as yet, unknown neuronal system that is regulated by these monoamine systems; 2. In both drug-free depressed patients and healthy subjects, tryptophan depletion and AMPT do not produce marked alterations in depressed mood. These results suggest that alterations in serotonin, dopamine, and noradrenaline systems may not reflect the primary pathology causing depressive illness. An alternative explanation is that in depressed patients these systems are maximally dysfunctional such that further manipulations do not worsen depressive systems. 3. Clinical experience and the results from several controlled studies indicate that the efficacy of SSRIs and noradrenaline inhibiting drugs are approximately equal.(ABSTRACT TRUNCATED AT 250 WORDS)
这些研究以及其他研究的结果为审慎地重新审视脑单胺功能在抑郁症病理生理学中的作用以及抗抑郁药物的作用机制提供了契机。以下观察结果最为突出：1. 色氨酸耗竭会降低脑血清素功能，可逆转特异性血清素再摄取抑制剂（SSRI）的治疗效果，但不会逆转强效抑制去甲肾上腺素再摄取药物的效果。相反，由于给予α-甲基对酪氨酸（AMPT）导致去甲肾上腺素和多巴胺耗竭，会逆转去甲肾上腺素（地昔帕明）和多巴胺（马吲哚）再摄取抑制剂所诱导的缓解，但不会逆转SSRI的效果。这些数据表明，抗抑郁药物的疗效可能并非源于涉及单一单胺系统的共同机制。SSRI和去甲肾上腺素再摄取抑制剂可能分别通过对血清素和去甲肾上腺素功能的主要作用来发挥作用。或者，这两类抗抑郁药物可能通过影响一个尚未明确的受这些单胺系统调节的神经元系统的功能来发挥其治疗特性；2. 在未服用药物的抑郁症患者和健康受试者中，色氨酸耗竭和AMPT都不会使抑郁情绪产生明显变化。这些结果表明，血清素、多巴胺和去甲肾上腺素系统的改变可能并不反映导致抑郁症的主要病理过程。另一种解释是，在抑郁症患者中，这些系统功能已极度失调，以至于进一步的操作不会使抑郁症状恶化。3. 临床经验和多项对照研究的结果表明，SSRI和去甲肾上腺素抑制药物的疗效大致相当。（摘要截选至250词）
