Ruhé Henricus G, Khoenkhoen Sharina J, Ottenhof Koen W, Koeter Maarten W, Mocking Roel J T, Schene Aart H
Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Mood and Anxiety Disorders, Groningen, The Netherlands.
Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Psychoneuroendocrinology. 2015 Feb;52:261-71. doi: 10.1016/j.psyneuen.2014.10.024. Epub 2014 Nov 26.
Hypothalamic-pituitary-adrenal (HPA)-axis dysregulation is a prominent finding in more severe Major Depressive Disorder (MDD), and is characterized by increased baseline cortisol levels at awakening (BCL), blunted cortisol awakening response (CAR) and increased area under the cortisol curve (AUC). Selective serotonin reuptake inhibitors (SSRIs) appear to normalize HPA-axis dysfunction, but this is hardly investigated longitudinally. We studied salivary BCL, CAR and AUC at awakening and 30min thereafter. We compared measurements in initially drug-free MDD-patients with healthy controls (HCs) at study-entry. In patients, we repeated measures after 6 and 12 weeks' treatment with the SSRI paroxetine. Non-responding patients received a randomized dose-escalation after six weeks' treatment. We found no significant study-entry differences in BLC, CAR or AUC between MDD-patients (n=70) and controls (n=51). In MDD-patients, we found general decreases of BCL and AUC during paroxetine treatment (p≤0.007), especially in late and non-responders. Importantly, while overall CAR did not change significantly over time, it robustly increased over 12 weeks especially when patients achieved remission (p≤0.041). The dose-escalation intervention did not significantly influence CAR or other cortisol parameters. In conclusion, paroxetine seems to interfere with HPA-axis dysregulation, reflected in significant overall decreases in BCL and AUC during treatment. Paroxetine appears to decrease HPA-axis set-point in MDD, which might result in increased HPA-axis activity over time, which is further improved when patients achieve remission (ISRCTN register nr. ISRCTN44111488).
下丘脑-垂体-肾上腺（HPA）轴功能失调是重度抑郁症（MDD）更为突出的一个表现，其特征为觉醒时的基线皮质醇水平（BCL）升高、皮质醇觉醒反应（CAR）迟钝以及皮质醇曲线下面积（AUC）增加。选择性5-羟色胺再摄取抑制剂（SSRIs）似乎可使HPA轴功能障碍恢复正常，但这方面的纵向研究几乎没有。我们研究了觉醒时及之后30分钟的唾液BCL、CAR和AUC。我们将最初未用药的MDD患者在研究开始时的测量结果与健康对照者（HCs）进行了比较。在患者中，我们在使用SSRI帕罗西汀治疗6周和12周后重复进行了测量。无反应的患者在治疗6周后接受随机剂量递增。我们发现MDD患者（n = 70）和对照者（n = 51）在研究开始时的BLC、CAR或AUC没有显著差异。在MDD患者中，我们发现帕罗西汀治疗期间BCL和AUC总体下降（p≤0.007），尤其是在晚期患者和无反应者中。重要的是，虽然总体CAR随时间没有显著变化，但在12周内它显著增加，尤其是当患者达到缓解时（p≤0.041）。剂量递增干预对CAR或其他皮质醇参数没有显著影响。总之，帕罗西汀似乎会干扰HPA轴功能失调，表现为治疗期间BCL和AUC总体显著下降。帕罗西汀似乎会降低MDD患者的HPA轴设定点，这可能会导致HPA轴活性随时间增加，当患者达到缓解时会进一步改善（国际标准随机对照试验编号：ISRCTN44111488）。
