Clinical Course, Therapy, Outcome and Analytical Data in Amitriptyline and Combined Amitriptyline/Chlordiazepoxide Overdose

Abstract

A total of 103 cases of amitriptyline (AT) overdose (group 1) and 81 cases of overdose with a fixed combination of AT and chlordiazepoxide (CDE) (group 2), treated at our Intensive Care Unit or reported to our Poison Information Center between 1985-1990, were evaluated with respect to clinical course, symptoms and outcome, as well as efficacy of therapy. The mean amount of AT was considerably higher in group 1 compared to group 2 (13 mg kg^-1 vs 7.7 mg kg^-1 ). The most frequent symptoms in both groups were impaired consciousness, anticholinergic symptoms, seizures, arrhythmia and hypotension. Respiratory insufficiency necessitated respirator therapy in 63 of the patients. Two patients in group 1 and one patient in group 2 did not survive. Therapy included primary detoxification by gastric lavage and repeated administration of activated charcoal. In four of eight patients with cardiac conduction disturbances, hypertonic sodium bicarbonate led to a significant reduction in QRS duration and AV interval. Physostigmine was effective in eight of 14 patients with pronounced anticholinergic symptoms. No effect was observed in the other six patients. Haemoperfusion, which was performed in five patients, led to rapid improvement of coma after initiation of therapy in four patients. The clinical efficacy of haemoperfusion in AT overdose despite the high volume of distribution of AT deserves further investigation. The rather high average overdose of AT implies that large package sizes of AT were available to the patients. A major step towards prevention of serious AT overdose would be the prescription of package sizes containing a total amount of less than 500 mg AT. Different analytical methods (enzyme immunoassay, fluorescence polarization immunoassay, and gas chromatography/mass spectrometry) for rapid detection of AT and its metabolites in plasma and urine were evaluated. Commercially available immunoassays like EMIT and ADX were highly reliable and sensitive in the detection of AT overdose. Five previously unknown metabolites or derivatives of AT could be detected in cases of AT overdose with the aid of a gas chromatography/mass spectrometry screening procedure.