DOES TOLERANCE DEVELOP TO THE SEDATIVE AND AMNESIC EFFECTS OF ANTIDEPRESSANTS ? : A COMPARISON OF AMITRIPTYLINE, TRAZODONE AND PLACEBO

Summary. The psychomotor, sedative and memory effects of a sedative, anticholinergic antidepressant (amitriptyline), a sedative antidepressant (trazodone) and placebo were compared in a double-blind, cross-over study with 12 healthy volunteers. Amitriptyline (37.5 mg) and trazodone (100 mg) were administered for the first 7 days of treatment and in double-dosage for the next 7 days of treatment. Subjects completed a battery of tests before and 2 h after drug administration on days 1, 8 and 14. Over the 2 weeks of treatment, there was no accumulation of effects but subjects experienced marked sedation and psychomotor impairments following a daily dose of both active drugs. Although both amitriptyline and trazodone produced impairments on memory tasks, the effect of amitriptyline was significantly greater and may reflect its anticholinergic action over and above global sedative effects. Tolerance to the effects of amitriptyline built up differentially over measures of sedation, psychomotor function and memory.