Cohrs Stefan, Pohlmann Kathrin, Guan Zhenghua, Jordan Wolfgang, Meier Andreas, Huether Gerald, Rüther Eckart, Rodenbeck Andrea
Department of Psychiatry and Psychotherapy, Georg-August-University of Göttingen, von-Siebold Strasse 5, 37075 Göttingen, Germany.
Psychopharmacology (Berl). 2004 Jul;174(3):414-20. doi: 10.1007/s00213-003-1766-6. Epub 2004 Jan 20.
Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a frequent finding in psychiatric disorders, including psychotic depression and schizophrenia. Conflicting results exist concerning the influence of antipsychotics on the HPA-axis.
Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the effect of quetiapine on nocturnal urinary cortisol and melatonin excretion in 13 healthy male subjects under conditions of undisturbed and experimentally disturbed sleep.
Volunteers were studied 3 times for 3 consecutive nights (N0, adaptation; N1, standard sleep conditions; N2, acoustic stress) 4 days apart. Placebo, quetiapine 25 mg or quetiapine 100 mg was administered orally 1 h before bedtime on nights 1 and 2. Urine produced during the 8-h bedtime period was collected for later determination of cortisol and melatonin concentrations by standard radioimmunoassays.
MANOVA showed a significant effect for N1 vs. N2 with elevated total amount of cortisol ( p<0.005) and melatonin ( p<0.05) excretion after acoustic stress. Both quetiapine 25 mg and 100 mg significantly ( p<0.0005) reduced the total amount of cortisol excretion in comparison to placebo. No interaction effect of stress condition was observed. There was no effect of quetiapine on melatonin levels.
The significant reduction of nocturnal cortisol excretion following quetiapine reflects a decreased activity of the HPA-axis in healthy subjects. This finding may be an important aspect in quetiapine's mode of action in different patient populations.
下丘脑 - 垂体 - 肾上腺（HPA）轴功能障碍在包括精神病性抑郁症和精神分裂症在内的精神疾病中很常见。关于抗精神病药物对HPA轴的影响存在相互矛盾的结果。
因此，这项双盲、安慰剂对照、随机交叉研究调查了喹硫平在13名健康男性受试者处于未受干扰和实验性干扰睡眠条件下对夜间尿皮质醇和褪黑素排泄的影响。
志愿者每隔4天连续3晚接受3次研究（N0，适应期；N1，标准睡眠条件；N2，声音应激）。在第1和第2晚睡前1小时口服安慰剂、25 mg喹硫平或100 mg喹硫平。收集8小时睡眠时间内产生的尿液，随后通过标准放射免疫分析法测定皮质醇和褪黑素浓度。
多变量方差分析显示，与N1相比，N2时声音应激后皮质醇总量（p<0.005）和褪黑素总量（p<0.05）排泄量增加，差异有统计学意义。与安慰剂相比，25 mg和100 mg喹硫平均显著（p<0.0005）降低了皮质醇排泄总量。未观察到应激条件的交互作用。喹硫平对褪黑素水平无影响。
喹硫平后夜间皮质醇排泄显著减少反映了健康受试者HPA轴活性降低。这一发现可能是喹硫平在不同患者群体中作用方式的一个重要方面。
