Williams S A, Wesnes K, Oliver S D, Rapeport W G
Pfizer Central Research, Sandwich, Kent, United Kingdom.
J Clin Psychiatry. 1996;57 Suppl 1:7-11.
This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects.
All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg/day from Days 9 to 16, and remained at 200 mg/day for the final 10 days of the drug administration period. Cognitive function testing was performed before dosing and over a 24-hour period after dosing on Days 1, 2, and 25.
Impairment of cognitive function was observed 6 to 8 hours after administration of haloperidol on Day 2 but was not evident 23 hours after dosing. When single-dose haloperidol was given again 25 days later, greater impairment with earlier onset was noted in several tests in both treatment groups, suggesting enhancement of this effect. There was no indication that sertraline exacerbated the impairment produced by haloperidol since an equivalent effect also occurred in the placebo group. Three subjects (2 on sertraline and 1 on placebo) withdrew from the study because of side effects. Ten subjects in each group reported side effects related to treatment. The side effect profiles of sertraline and of placebo were similar.
Haloperidol produced a clear profile of cognitive impairment that was not worsened by concomitant sertraline administration.
这项双盲、随机、安慰剂对照研究评估了单独使用氟哌啶醇以及氟哌啶醇加舍曲林对24名健康男性受试者认知和精神运动功能的影响。
所有受试者在第1天接受安慰剂，在第2天和第25天接受2毫克氟哌啶醇。从第9天至第25天，受试者被随机分为舍曲林组（12名受试者）或安慰剂组（12名受试者）；舍曲林剂量在第9天至第16天从50毫克/天滴定至200毫克/天，并在给药期的最后10天维持在200毫克/天。在第1、2和25天给药前及给药后的24小时内进行认知功能测试。
在第2天给予氟哌啶醇后6至8小时观察到认知功能损害，但给药23小时后不明显。25天后再次给予单剂量氟哌啶醇时，两个治疗组的多项测试中均出现了更早发作的更严重损害，表明这种效应增强。没有迹象表明舍曲林会加剧氟哌啶醇产生的损害，因为安慰剂组也出现了同等效应。三名受试者（2名服用舍曲林，1名服用安慰剂）因副作用退出研究。每组有10名受试者报告了与治疗相关的副作用。舍曲林和安慰剂的副作用情况相似。
氟哌啶醇产生了明显的认知损害特征，同时服用舍曲林不会使其恶化。
