Kozak M J, Rossi M, McCarthy P R, Foa E B
Medical College of Pennsylvania, Eastern Pennsylvania Psychiatric Institute, Philadelphia 19129.
Biol Psychiatry. 1989 Nov;26(7):707-16. doi: 10.1016/0006-3223(89)90105-4.
It has been argued that a mechanism of clomipramine's efficacy for obsessive-compulsive disorder is its reduction of excessive autonomic reactivity. The present study evaluated this proposed mechanism of action by assessing the effect on autonomic responding of imipramine, which is structurally similar to clomipramine, but lacks therapeutic efficacy for obsessive-compulsives. Twenty-three obsessive-compulsive patients received three sessions of 20 unsignalled 1000-Hz, 100-dB tones of 1-sec duration and 100-msec rise-time. Skin conductance level, response frequency and magnitude, and heart rate were scored for an adaptation period and for each tone onset. Six weeks after the first tone session, during which half of the subjects received imipramine while the remainder received placebo, the second tone assessment was performed. A third tone assessment was performed after an additional 4 weeks of medication. Percentage of nonresponders was also evaluated for each group. Imipramine reduced electrodermal activity and increased heart rate. Skin conductance level and both number and amplitude of responses decreased significantly after 6 weeks of imipramine, compared with placebo, with further attenuation of electrodermal activity after 10 weeks of the drug. Electrodermal nonresponding increased dramatically for the imipramine group as compared to the nondrug group. These results reveal effects of imipramine on autonomic responding, and cast doubt on the hypothesis that a mechanism for successful drug treatment of obsessive-compulsive disorder is decreased autonomic reactivity.
有人认为，氯米帕明治疗强迫症有效的一种机制是它能降低过度的自主反应性。本研究通过评估与氯米帕明结构相似但对强迫症缺乏治疗效果的丙咪嗪对自主反应的影响，来评价这一提出的作用机制。23名强迫症患者接受了3次测试，每次测试有20次无信号的1000赫兹、100分贝、持续1秒且上升时间为100毫秒的音调。对适应期以及每个音调开始时的皮肤电导水平、反应频率和幅度以及心率进行评分。在第一次音调测试六周后进行第二次音调评估，在此期间，一半受试者服用丙咪嗪，其余受试者服用安慰剂。在额外用药4周后进行第三次音调评估。还对每组的无反应者百分比进行了评估。丙咪嗪降低了皮肤电活动并增加了心率。与安慰剂相比，服用丙咪嗪6周后，皮肤电导水平以及反应的数量和幅度均显著下降，用药10周后皮肤电活动进一步减弱。与未用药组相比，丙咪嗪组的皮肤电无反应情况显著增加。这些结果揭示了丙咪嗪对自主反应的影响，并对强迫症成功药物治疗的机制是自主反应性降低这一假设提出了质疑。
