David S R, Taylor C C, Kinon B J, Breier A
Lilly Research Laboratories, Eli Lilly and Company, Eli Corporate Center, Indianapolis, Indiana 46285 USA.
Clin Ther. 2000 Sep;22(9):1085-96. doi: 10.1016/S0149-2918(00)80086-7.
There is relatively little comparative information on elevations in plasma prolactin level (PRL) with conventional versus novel antipsychotic agents.
This paper examines the comparative effects on PRL of olanzapine, risperidone, and haloperidol based on data from 3 multicenter, double-blind, randomized clinical trials. Magnitude of response, dose dependency, time course, effects of sex and age, and response to switching from haloperidol to olanzapine are assessed.
The effects of olanzapine, risperidone, and haloperidol on PRL were assessed in patients with schizophrenia or related psychoses participating in 3 double-blind clinical trials: (1) a 6-week acute trial comparing olanzapine 5 to 20 mg/d (n = 1,336) and haloperidol 5 to 20 mg/d (n = 660), with a 1-year, open-label olanzapine extension for responders; (2) a 54-week study comparing olanzapine 5 to 20 mg/d (n = 21), risperidone 4 to 10 mg/d (n = 21), and haloperidol 5 to 20 mg/d (n = 23) in early illness; and (3) a 28-week study comparing olanzapine 10 to 20 mg/d (n = 172) and risperidone 4 to 12 mg/d (n = 167).
PRL elevations were significantly greater with risperidone than with either olanzapine or haloperidol in study 2. and significantly greater than with olanzapine in study 3 (all, P < 0.001). PRL elevations were significantly greater with haloperidol than with olanzapine in study 1 (P < 0.001 ). A dose-response relationship was not consistently confirmed with any of the drug treatments. Risperidone-associated PRL elevations peaked relatively early in treatment. In haloperidol- and risperidone-treated patients, the mean change in PRL was greater in women than in men. PRL decreased significantly when treatment was switched from haloperidol to olanzapine.
This side-by-side analysis of 3 independent studies suggests that with the 3 antipsychotic drugs studied, PRL is elevated moderately by olanzapine (mean change, 1-4 ng/mL), intermediately by haloperidol (mean change, approximately 17 ng/mL), and strongly by risperidone (mean change, 45-80 ng/mL). No consistent dose-response relationship was observed, and the time course and sex-dependency of the response differed between the 3 agents. Patients with haloperidol-induced hyperprolactinemia may benefit from a switch to olanzapine. Long-term studies examining the health consequences of chronic hyperprolactinemia during antipsychotic treatment are needed.
关于传统抗精神病药物与新型抗精神病药物导致血浆催乳素水平（PRL）升高的比较信息相对较少。
本文基于3项多中心、双盲、随机临床试验的数据，研究奥氮平、利培酮和氟哌啶醇对PRL的比较影响。评估反应程度、剂量依赖性、时间进程、性别和年龄的影响，以及从氟哌啶醇换用奥氮平的反应。
在参与3项双盲临床试验的精神分裂症或相关精神病患者中，评估奥氮平、利培酮和氟哌啶醇对PRL的影响：（1）一项为期6周的急性试验，比较奥氮平5至20mg/d（n = 1336）和氟哌啶醇5至20mg/d（n = 660），对反应者进行为期1年的开放标签奥氮平延长治疗；（2）一项为期54周的研究，比较早期疾病中奥氮平5至20mg/d（n = 21）、利培酮4至10mg/d（n = ）和氟哌啶醇5至20mg/d（n = 23）；（3）一项为期28周的研究，比较奥氮平10至20mg/d（n = 172）和利培酮4至12mg/d（n = 167）。
在研究2中，利培酮导致的PRL升高显著高于奥氮平和氟哌啶醇；在研究3中，利培酮导致的PRL升高显著高于奥氮平（均P < 0.001）。在研究1中，氟哌啶醇导致的PRL升高显著高于奥氮平（P < 0.001）。未一致确认任何一种药物治疗存在剂量反应关系。利培酮相关的PRL升高在治疗早期达到峰值。在接受氟哌啶醇和利培酮治疗的患者中，女性PRL的平均变化大于男性。从氟哌啶醇换用奥氮平治疗后，PRL显著下降。
这一针对3项独立研究的并列分析表明，在所研究的3种抗精神病药物中，奥氮平使PRL适度升高（平均变化1 - 4 ng/mL），氟哌啶醇使其中度升高（平均变化约17 ng/mL），利培酮使其显著升高（平均变化45 - 80 ng/mL）。未观察到一致的剂量反应关系，且这3种药物的反应时间进程和性别依赖性有所不同。氟哌啶醇所致高催乳素血症患者换用奥氮平可能有益。需要进行长期研究以考察抗精神病治疗期间慢性高催乳素血症对健康的影响。
