Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving

Twenty healthy subjects took amitriptyline, doxepin, and placebo for 2 wk each in a double‐blind crossover trial, and another 20 subjects similarly took nortriptyline, chlorimipramine, and placebo. The antidepressants were given three times daily in doses generally used for neurotic patients. The presence of antidepressants in tissues was checked with the tyramine pressor test. On the seventh and fourteenth days of each period, psychomotor skills (choice reaction, coordination, and attention) were measured after the administration of drugs in combination with an alcoholic or placebo drink. Dose‐response graphs for the tyramine pressor effect were shifted to the right during the antidepressant treatment, indicating a blockade of the membrane pump in peripheral sympathetic terminals. This anti tyramine effect of antidepressants did not correlate with their psychomotor effects. No drug alone importantly impaired psychomotor skills. Amitriptyline in combination with alcohol increased cumulative choice reaction times, and doxepin in combination with alcohol increased both cumulative choice reaction times and inaccuracy of reactions. Coordination was impaired after both of these combinations on the seventh day. It seems as if doxepin and amitriptyline but not nortriptyline or chlorimipramine, in combination with 0.5 gm/kg of alcohol, may be especially dangerous in driving.