CONSIDERING THE P450 CYTOCHROME SYSTEM AS DETERMINING COMBINED EFFECTS OF ANTIDEPRESSANTS AND BENZODIAZEPINES ON ACTUAL DRIVING PERFORMANCEOF DEPRESSED OUTPATIENTS

Parallel groups of depressed (DSM III-R) outpatients received moclobem ide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respe ctive starting doses were 150 mg twice a day and 20 mg q.a.m. These co uld be doubled after 3 weeks for greater efficacy. Chronic users of be nzodiazepine anxiolytics continued taking them as comedication. Therap eutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therap y and at 1, 3 and 6 weeks thereafter using a standardized test that me asures standard deviation of lateral position (SDLP). Similar remissio ns in depressive symptoms and side effects occurred in both groups. Pa tients drove with normal and reliable (r = 0.87) SDLPs before treatmen ts. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03 ). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginni ng of therapy. At 3 and 6 weeks there were significant (p < 0.03) rela tionships involving the same factor; patients who drove with progressi vely higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particula r antidepressant.