Effects of imipramine on the autonomic responses of obsessive-compulsives to auditory tones

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.