Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):308-13. doi: 10.3109/15622970701639429.
Among the neuroactive steroids, 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA) system. The antidepressant mirtazapine has been shown to attenuate HPA axis activity and to increase the concentrations of 3alpha-reduced metabolites of progesterone in depressed patients. In the present study, the impact of mirtazapine on 3alpha,5alpha-THDOC levels was investigated in relation to clinical response in depressed patients.
A total of 23 drug-free inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 08:00 h and were quantified for 3alpha,5alpha-THDOC levels.
3alpha,5alpha-THDOC levels were not correlated with demographic and clinical parameters such as age and severity of depression. Moreover, 5-week treatment with mirtazapine did not influence the 3alpha,5alpha-THDOC in the depressed patients, neither in responders nor in non-responders.
Putative increasing effects of mirtazapine on 3alpha-reduced neuroactive steroids such as 3alpha,5alpha-THDOC which may be mediated via an impact on the neurosteroidogenic enzyme 3alpha-hydroxysteroid dehydrogenase seem to be counterbalanced by the mirtazapine-induced inhibition of ACTH secretion which directly influences the 3alpha,5alpha-THDOC release of the adrenal cortex.
在神经活性甾体中,3α,5α-四氢脱氧皮质酮(3α,5α-THDOC)至少部分在肾上腺中产生,因此受下丘脑-垂体-肾上腺皮质(HPA)系统的控制。抗抑郁药米氮平已被证明可减弱 HPA 轴的活性,并增加抑郁患者中孕酮的 3α-还原代谢物的浓度。在本研究中,研究了米氮平对 3α,5α-THDOC 水平的影响与抑郁患者的临床反应有关。
共有 23 名未服用药物的住院抑郁症患者(DSM-IV 标准)接受米氮平(45mg/天)治疗 5 周。每周在 08:00 时采集血浆样本,并定量检测 3α,5α-THDOC 水平。
3α,5α-THDOC 水平与年龄和抑郁严重程度等人口统计学和临床参数无关。此外,米氮平治疗 5 周并未影响抑郁患者的 3α,5α-THDOC,无论是在反应者还是非反应者中。
米氮平对 3α-还原神经活性甾体(如 3α,5α-THDOC)的推定增加作用可能是通过对神经甾体生成酶 3α-羟甾脱氢酶的影响介导的,但被米氮平诱导的 ACTH 分泌抑制所抵消,后者直接影响肾上腺皮质的 3α,5α-THDOC 释放。