OBJECTIVE We have previously reported higher brain serotonin 1A (5-HT1A ) autoreceptor binding in antidepressant-naïve patients with Major Depressive Disorder (MDD) compared with healthy volunteers, and a decrease in binding in MDD after selective serotonin reuptake inhibitor (SSRI) treatment. This SSRI effect is also present in rodents administered SSRIs chronically. We therefore sought to determine the duration of antidepressant medication effects on 5-HT1A receptor binding after medication discontinuation. METHODS Positron emission tomography (PET) imaging with the 5-HT1A receptor radioligand [11 C]WAY-100635 was performed in 66 individuals with current DSM-IV MDD to examine relationships between 5-HT1A binding and time since most recent antidepressant treatment. All subjects were medication-free for at least 2 weeks prior to scanning. Thirty-two additional MDD comparison subjects were antidepressant naïve. RESULTS No differences in [11 C]WAY-100635 binding were observed between antidepressant naïve and antidepressant exposed MDD groups in 13 a priori cortical and subcortical regions of interest, including raphe autoreceptors, assessed simultaneously in linear mixed effects models. Furthermore, [11 C]WAY-100635 binding did not correlate with time off antidepressants in the antidepressant exposed patients considering these ROIs. The same results were observed when effects of treatment discontinuation of any psychotropic medication used to treat their depression was examined. CONCLUSION These results indicate that any antidepressant-associated downregulation of 5-HT1A autoreceptor binding reverses within 2 weeks of medication discontinuation. Since this effect is hypothesized to mediate the antidepressant action of SSRIs, and perhaps other antidepressants, it suggests that patients who need ongoing treatment may relapse rapidly when medication is discontinued. Moreover, 2 weeks appears to be a sufficiently long washout of antidepressant medications for a reliable measure of illness-related binding levels.

中文翻译：

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重度抑郁症患者的抗抑郁药物暴露和5-HT1A自身受体结合。

目的我们以前报道过，与健康志愿者相比，初次服用抗抑郁药的重度抑郁症（MDD）患者中的血清素1A（5-HT1A）自体受体结合水平更高，选择性5-羟色胺再摄取抑制剂（SSRI）治疗后MDD的结合降低。长期施用SSRI的啮齿动物也存在这种SSRI效应。因此，我们寻求确定停药后抗抑郁药对5-HT1A受体结合的作用持续时间。方法用5-HT1A受体放射性配体[11 C] WAY-100635进行正电子发射断层扫描（PET）成像，研究了66位具有当前DSM-IV MDD的患者，以检查自最近抗抑郁治疗以来5-HT1A结合与时间之间的关系。扫描前，所有受试者至少2周无药物治疗。另有32名MDD比较对象是单纯的抗抑郁药。结果在线性混合效应模型中，同时评估了13个先验皮质和皮质下感兴趣区域（包括瑞夫自体受体）中未接受过抗抑郁药的和未接受过抗抑郁药的MDD组之间在[11 C] WAY-100635结合方面未见差异。此外，考虑到这些ROI，在接受抗抑郁药治疗的患者中，[11 C] WAY-100635的结合与抗抑郁药的停用时间无关。当检查用于治疗抑郁症的任何精神药物的治疗中断效果时，观察到相同的结果。结论这些结果表明，与抗抑郁药相关的5-HT1A自身受体结合的下调在停药2周内会逆转。由于该作用被认为可以介导SSRIs的抗抑郁作用，也许还可以介导其他抗抑郁药的作用，这表明需要中止治疗的患者可能会在停药后迅速复发。而且，对于可靠地测量与疾病相关的结合水平，抗抑郁药物的冲洗时间似乎足够长，为2周。