Ramaekers Johannes G
Experimental Psychopharmacology Unit, Brain & Behavior Institute, Maastricht University, Maastricht, The Netherlands.
J Clin Psychiatry. 2003 Jan;64(1):20-9.
The current review summarizes the major results from all published studies from 1983 to 2000 (9 double-blind, crossover, placebo-controlled studies in healthy volunteers and 1 double-blind, baseline-controlled study in patients) that have determined the effects of antidepressants on actual driving performance using a standard test. That test measures driving impairment from vehicular "weaving" (i.e., standard deviation of lateral position [SDLP]) during 1 hour of on-the-road driving in normal traffic.
Changes in SDLP after acute doses of sedating antidepressants (i.e., amitriptyline, imipramine, doxepin, and mianserin) were comparable to those seen in drivers conducting the same test with a blood alcohol concentration of 0.8 mg/mL or more. Driving performance of subjects returned to placebo levels after 1 week of treatment, except after treatment with mianserin, for which the impairing effect lasted unabated over treatment. Nocturnal doses of sedating antidepressants (i.e., dothiepin, mianserin, and mirtazapine), however, did not produce residual driving impairment when measured the next day. Nonsedating antidepressants (i.e., moclobemide, fluoxetine, paroxetine, venlafaxine, and nefazodone) generally did not affect SDLP. However, SDLP rose to unacceptable levels after administration of combinations of nonsedating antidepressants and benzodiazepines with incompatible pharmacokinetic profiles. Correlational analyses demonstrated that conventional tests of psychomotor performance or self-ratings of side effects did not strongly predict antidepressant effects on SDLP. Regression analysis revealed a strong linear relation between antidepressant effects in the standard driving test and the number of patients reporting somnolence in clinical trials with the same antidepressants.
Application of actual driving tests remains essential to conclusively defining the potential hazard of drugs for driving.
本综述总结了1983年至2000年期间所有已发表研究(9项针对健康志愿者的双盲、交叉、安慰剂对照研究以及1项针对患者的双盲、基线对照研究)的主要结果,这些研究使用标准测试确定了抗抑郁药对实际驾驶性能的影响。该测试通过测量正常交通状况下1小时道路驾驶过程中车辆“摆动”(即横向位置标准差[SDLP])导致的驾驶能力受损情况。
急性给予镇静性抗抑郁药(即阿米替林、丙咪嗪、多塞平及米安色林)后SDLP的变化与血液酒精浓度达到或超过0.8mg/mL的驾驶员进行相同测试时的变化相当。除米安色林治疗外,受试者的驾驶性能在治疗1周后恢复至安慰剂水平,米安色林的损害作用在整个治疗过程中持续未减。然而,夜间给予镇静性抗抑郁药(即多塞平、米安色林及米氮平),次日测量时未产生残留驾驶能力损害。非镇静性抗抑郁药(即吗氯贝胺、氟西汀、帕罗西汀、文拉法辛及奈法唑酮)一般不影响SDLP。然而,给予药代动力学特征不兼容的非镇静性抗抑郁药与苯二氮䓬类药物组合后,SDLP升至不可接受的水平。相关性分析表明,传统的精神运动性能测试或副作用自评并不能有力地预测抗抑郁药对SDLP的影响。回归分析显示,标准驾驶测试中的抗抑郁药效应与使用相同抗抑郁药的临床试验中报告嗜睡的患者数量之间存在强线性关系。
实际驾驶测试对于最终确定药物驾驶潜在危害仍然至关重要。