VERBAL-LEARNING BY MAJOR DEPRESSIVE DISORDER PATIENTS DURING TREATMENT WITH FLUOXETINE OR AMITRIPTYLINE

After 1 week of a single-blind placebo period, and prior to being rand omly assigned to receive treatment with either fluoxetine or amitripty line, patients meeting strict criteria for a diagnosis of major depres sive disorder were given an auditory verbal learning test of working m emory, and a blood sample was drawn. After 3 weeks of drug treatment w ith either amitriptyline or fluoxetine, the patients' symptoms were ev aluated, the verbal learning test was repeated, and a second blood sam ple was taken. The clinical evaluation, the verbal learning test and t he blood drawing were repeated a third time 3 weeks after the second a ssessment. The amount of anticholinergic activity in the blood samples was measured by a competitive radioligand binding assay and expressed in atropine equivalents. Analyses of variance indicated that there we re no significant differences at the predrug Assessment I between pati ents subsequently assigned to the fluoxetine group compared with those assigned to the amitriptyline group. At Assessments 2 and 3, the fluo xetine and the amitriptyline groups showed equal clinical improvement but patients receiving amitriptyline did not perform as well on the ve rbal learning task. Serum anticholinergic activity at Assessments 2 an d 3 was considerably higher in the amitriptyline group. This supports the hypothesis that blockade of muscarinic receptors impairs working m emory formation. Equally effective antidepressant drugs with little or no anticholinergic action, such as fluoxetine, may be preferable in p atients with pre-existing mild cognitive impairment or in patients whe re a slight reduction in cognitive performance is not acceptable.