title: Considering the P450 cytochrome system as determining combined effects of antidepressants and benzodiazepines on actual driving performance of depressed outpatients.
abstract: Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. 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 beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.
authors.affiliation: Institute for Human Psychopharmacology, Maastricht University, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Ramaekers
authors.forename: M
authors.initials: M
authors.lastname: Ansseau
authors.forename: N D
authors.initials: ND
authors.lastname: Muntjewerff
authors.forename: J P
authors.initials: JP
authors.lastname: Sweens
authors.forename: J F
authors.initials: JF
authors.lastname: O'Hanlon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001334:Automobile Driving / Q000523:psychology*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use; D001569:Benzodiazepines; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003866:Depressive Disorder / Q000201:enzymology* / Q000523:psychology*; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D001569:Benzodiazepines; D003577:Cytochrome P-450 Enzyme System; D016666:Fluvoxamine; D020912:Moclobemide