Amitriptyline selectively disrupts verbal recall from secondary memory of the normal aged

Amitriptyline, a frequently prescribed tricyclic antidepressant, is reported to produce an age-related impairment in anterograde memory. However, the locus of this adverse effect has never been described within the context of contemporary learning and memory theory. Fifteen normal elderly subjects were treated with 50 mg amitriptyline and placebo in a cross-over study. A computerized stage analysis of memory revealed that sensory and primary memory were not affected while verbal recall from secondary memory was markedly disrupted by amitriptyline. Further examination of secondary memory revealed that amitriptyline impaired recall, but not recognition. The profile of anterograde memory impairments observed with amitriptyline is similar to that previously reported for the antimuscarinic, scopolamine. Since amitriptyline at the dose employed in this study would be expected to exert marked central antimuscarinic effects, it appears likely that it is the pharmacologic blockade of central muscarinic receptors in the aged that results in the selective disruption of verbal recall in secondary memory.