Long-term versus short-term amitriptyline side effects as measured by a postmarketing surveillance system

As part of a large-scale postmarketing surveillance study, the adverse clinical events (ACEs) reported by 85 outpatients taking amitriptyline were investigated. Two discrete groups of patients were identified based on their duration of amitriptyline treatment: 45 had started the drug within 2 weeks of their interview (mean = 10.1 days, SD = 1.6 days), while 40 were much longer term tricyclic antidepressant patients (mean = 227.2 days, SD = 135 days). Our analysis of amitriptyline side effects reported by each of these two discrete groups challenges the common clinical impression that tricyclic side effects, in general, abate with continued treatment. Shorter term patients were much better able to correctly attribute their adverse clinical events to their drug therapy. Anticholinergic side effects were reported as new symptoms by the long-term patients just as frequently with similar ratings of subjective severity. These reports of adverse drug reactions of recent onset by long-term amitriptyline users may reflect the fact that such symptoms fluctuate in their occurrence and may not be recognized as potentially drug-induced until some threshold for patient tolerance is exceeded.