Why some depressed patients may have low platelet 3H-imipramine binding

Human platelet membranes were incubated with 3H-imipramine, 3H-paroxetine or 3H-chlorimipramine. It was found that chlorimipramine remained in the membranes, as it was impossible to remove this antidepressant drug by normal washing procedures. Similar results, although to a lesser degree, were found with paroxetine, whereas imipramine could be washed away from the membranes. Treatment of volunteers with chlorimipramine strongly reduced platelet imipramine binding probably due to the presence of chlorimipramine in the membranes during the binding assay. These results suggest that the low imipramine binding reported in depressed patients, at least in some cases, may have been caused by antidepressant drugs or drug metabolites remaining in the platelet membrane preparations.