Reduced inhibitory effect of imipramine on radiolabeled serotonin uptake into platelets in geriatric depression

Tritiated imipramine binding, uptake of radiolabeled serotonin, and inhibition of uptake by imipramine in vitro were studied in platelets obtained from four groups of subjects: (1) normal controls 50 years of age or younger, (2) patients with major depression 50 years of age or younger, (3) normal controls 60 years of age or older, and (4) patients with major depression 60 years of age or older. Depression in both age groups was associated with a substantial decrease in the number of [3H]imipramine binding sites; the elderly depressed patients exhibited a small but significant (p less than 0.05) reduction in platelet [3H]serotonin uptake. However, the inhibition of serotonin uptake into platelets by imipramine was markedly reduced only in the elderly depressed patients. This reduced sensitivity to imipramine may explain the reduced responsiveness of patients with geriatric depression to the therapeutic effects of imipramine and other tricyclic antidepressants.