Schüle Cornelius, Baghai Thomas C, di Michele Flavia, Eser Daniela, Pasini Augusto, Schwarz Markus, Rupprecht Rainer, Romeo Elena
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336 Munich, Germany.
Psychoneuroendocrinology. 2007 Jul;32(6):669-80. doi: 10.1016/j.psyneuen.2007.04.004. Epub 2007 Jun 8.
Antidepressants such as SSRIs or mirtazapine have been demonstrated to increase the concentrations of 3alpha-reduced neuroactive steroids throughout several weeks of treatment. However, no data are available on the impact of mood stabilizers such as lithium or carbamazepine on neuroactive steroid levels in depressed patients. Study 1 was performed in 26 drug-free depressed inpatients who were treated with either mirtazapine monotherapy (n=13) or combination therapy with mirtazapine and addition of lithium (n=13). Twenty drug-free depressed inpatients were included in study 2, receiving either mirtazapine monotherapy (n=10) or combination treatment with mirtazapine and carbamazepine (n=10). Plasma samples were taken weekly at 0800 h in the morning and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. In study 1, the mirtazapine-induced rises in 3alpha,5alpha-tetrahydroprogesterone and 3alpha,5beta-tetrahydroprogesterone were abolished by additional lithium administration, as compared to mirtazapine monotherapy. In study 2, the mirtazapine-evoked increase in 3alpha,5alpha-tetrahydroprogesterone was reversed after additional administration of carbamazepine, presumably due to lowered mirtazapine levels after induction of cytochrome P450 enzymes. Apparently, the mood stabilizers lithium and carbamazepine do not enhance but rather reverse the increase in plasma concentrations of 3alpha-reduced neuroactive steroids in depressed patients pretreated with antidepressants such as mirtazapine.
选择性5-羟色胺再摄取抑制剂（SSRIs）或米氮平之类的抗抑郁药已被证明，在数周的治疗过程中可提高3α-还原神经活性甾体的浓度。然而，关于锂盐或卡马西平之类心境稳定剂对抑郁症患者神经活性甾体水平的影响，尚无可用数据。研究1纳入了26例未服用过药物的抑郁症住院患者，这些患者接受米氮平单一疗法（n = 13）或米氮平联合锂盐疗法（n = 13）。研究2纳入了20例未服用过药物的抑郁症住院患者，他们接受米氮平单一疗法（n = 10）或米氮平联合卡马西平疗法（n = 10）。每周上午8点采集血浆样本，通过气相色谱/质谱联用分析法对神经活性甾体进行定量分析。在研究1中，与米氮平单一疗法相比，额外给予锂盐后，米氮平引起的3α,5α-四氢孕酮和3α,5β-四氢孕酮升高被消除。在研究2中，额外给予卡马西平后，米氮平引起的3α,5α-四氢孕酮升高被逆转，这可能是由于细胞色素P450酶诱导后米氮平水平降低所致。显然，对于先用米氮平之类抗抑郁药治疗的抑郁症患者，心境稳定剂锂盐和卡马西平并不会提高，反而会逆转3α-还原神经活性甾体的血浆浓度升高。
