精神分裂症帕罗西汀激发试验及其与疗效的关系

目的探讨精神分裂症中枢5-羟色胺（5－HT）、多巴胺（DA）功能，以及非典型、典型抗精神病药对它们的影响。方法采用随机、双盲法应用固定剂量利培酮6mg/d、氟哌啶醇20mg／d治疗78例精神分裂症患者，共12周。治疗前后测定皮质醇、催乳素对帕罗西汀激发试验的反应，并以18名正常人为对照组。结果治疗前患者组基础皮质醇（106±41）μg/L]、皮质醇对帕罗西汀激发试验的反应（曲线下面积AUC为717±229）高于对照组（73±25）μg／L及AUC585±163]，而基础催乳素（5±7）μg/L]低于对照组（9±5）μg／L]、催乳素对帕罗西汀激发试验的应答比对照组呈降低趋势（AUC49±41对68±43，P＞0．05）。治疗后，两组患者的催乳素基础值比治疗前均增高（P均＜0.05）；两组之间帕罗西汀介导的催乳素反应差异无显著性。治疗后，两组皮质醇的基础值（74±32）μg/L及（82±27）μg/L]均较治疗前降低，其中利培酮治疗后降低更为明显。利培酮治疗后皮质醇对帕罗西汀激发试验的反应（AUC518±213）降低，并与对照组差异无显著性，而氟哌啶醇组皮质醇反应与治疗前差异光显著性（P＞0．05）。结论精神分裂症患者治疗前可能有中枢DA功能亢进和5－HT功能增高。利培酮治疗使患者原来过高的中枢5－HT功能接近正常，而氟哌啶醇

Effects of risperidone and haloperidol on paroxetine-evoked neuroendocrine responses in schizophrenia

Objective The study was to explore the serotonergic and dopeminergic function in centralnervous system and to determine the pharmacological mechanisms of typical and atypical antipsychotics. Methods78 inpatients with schizophrenia were treated with a fixed dose of risperidone 6 mg daily or haloperidol 20 mg perday for 12-week in a double-blind, randomized design. The symptoms were evaluated by PANSS before and aftertreatment. Prolactin and cortisol responses to paroxetine challenge test were measured at pre- and post-treatment,as compared with 18 normal controls. Results At pre-treatment, baseline cortisol level and paroxetine-evokedcortisol response was significantly higher but baseline prolactin level was significantly lower paroxetine-stimulatedprolactin level in patient group. After treatment, the baseline prolactin levels of patients in both risperidone andhaloperidol groups were significantly increased and higher than that of normal control. No difference in prolactinresponse to paroxetine stimulation was noted between risperidone and haloperidol groups. Baseline cortisol levelswere markedly lower in both treatment groups than before treatment but a significant reduction for risperidonegroup. There was a significant decrease in cortisol response to paxoxetine challenge test in risperidone treatmentgroup but no difference in haloperidol treatment group when compared with both before treatment and normalcontrol. Conclusions The hyperactivity of dopamine and serotonin function may exist in patients withschizophrenia before treatment. Risperidone treatment can reduce the elevated 5-HT function of patient to normallevel. But haloperidol treatment doesn't produce significant influence on 5-HT function. Both risperidone andhaloperidol can ichibit the dopamine function considerably in the central nervous system.