Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders
Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders
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DOI：
10.1016/s0924-977x(99)00030-9
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发表时间：
1999-07-01
影响因子：
5.6
通讯作者：
Argyropoulos, S
中科院分区：
文献类型：
--
作者：
Nutt, DJ;Forshall, S;Argyropoulos, S
选择性血清素再摄取抑制剂（SSRI）已被证明对抑郁症和焦虑症有效。这就提出了一个问题：血清素再摄取抑制的单一作用如何能够改善多种精神疾病。为了理解这一明显的悖论，有必要考虑 SSRIs 在抑郁症或焦虑症的致病过程中发挥的作用。色氨酸消耗已广泛用于抑郁症研究，并表明，在接受 SSRI 且抑郁症已缓解的患者中，消耗血清素会导致疾病复发。对于惊恐障碍也有类似的结果。这表明，为了有效治疗抑郁症和恐慌症，突触中血清素水平的增加是 SSRI 所必需的。在强迫症中，服用 SSRI 恢复的患者血清素消耗不会导致复发；受体适应可能更重要。 SSRI 药物类别内的差异，例如血清素与去甲肾上腺素摄取的选择性比、消除半衰期以及对 5-HT2 受体的亲和力已被确定，并且可能是疗效、副作用和临床使用的重要决定因素。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use. (C) 1999 Elsevier Science B.V. All rights reserved.