Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, New York.
Synapse. 2019 Jun;73(6):e22089. doi: 10.1002/syn.22089. Epub 2019 Feb 19.
We have previously reported higher brain serotonin 1A (5-HT ) 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-HT receptor binding after medication discontinuation.
Positron emission tomography (PET) imaging with the 5-HT receptor radioligand [ C]WAY-100635 was performed in 66 individuals with current DSM-IV MDD to examine relationships between 5-HT 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.
No differences in [ 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, [ 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.
These results indicate that any antidepressant-associated downregulation of 5-HT 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.
我们之前曾报道过，与健康志愿者相比，未经抗抑郁药物治疗的重度抑郁症（MDD）患者大脑中血清素 1A（5-HT1A）自身受体结合更高，而在接受选择性 5-羟色胺再摄取抑制剂（SSRI）治疗后结合减少。这种 SSRI 效应也存在于长期给予 SSRI 的啮齿动物中。因此，我们试图确定停药后抗抑郁药物对 5-HT 受体结合的持续时间。
使用 5-HT 受体放射性配体 [C]WAY-100635 通过正电子发射断层扫描（PET）对 66 名当前 DSM-IV MDD 个体进行成像，以检查 5-HT 结合与最近抗抑郁治疗后时间之间的关系。所有患者在扫描前至少有 2 周没有服用药物。另外 32 名 MDD 比较受试者未经抗抑郁药物治疗。
在 13 个预先设定的皮质和皮质下感兴趣区域（包括同时在线性混合效应模型中评估的中缝自动受体）中，未观察到未经抗抑郁药物治疗和暴露于抗抑郁药物的 MDD 组之间的 [C]WAY-100635 结合存在差异。此外，在考虑到这些 ROI 的情况下，在暴露于抗抑郁药物的患者中，[C]WAY-100635 结合与停药时间无关。当检查用于治疗其抑郁症的任何精神药物停药的治疗效果时，观察到相同的结果。
这些结果表明，抗抑郁药相关的 5-HT 自身受体结合的下调在停药后 2 周内逆转。由于这种效应被假设为介导 SSRI 的抗抑郁作用，也许还有其他抗抑郁药，这表明当药物停止使用时，需要持续治疗的患者可能会迅速复发。此外，2 周似乎是抗抑郁药物可靠测量疾病相关结合水平的足够长的洗脱期。
