Tropatepine poisoning and management: a series of 458 cases

Tropatepine is an antiparkinsonian drug that can be associated with antimuscarinic delirium in overdose. Two acetylcholinesterase inhibitors, neostigmine and physostigmine, are available for the management of tropatepine poisoning. The aim of this study is to describe a series of tropatepine poisonings and to compare the management of patients.

This epidemiological, retrospective, multicentre study reviewed tropatepine intoxications reported to French poison centres from 1 January 2000 to 13 July 2023. The relationship between reduction in central antimuscarinic signs and associated risk factors was assessed by univariate and multivariate logistic regression.

A total of 458 cases of tropatepine poisoning were included. Peripheral and central antimuscarinic signs were observed in 214 (46.7%) and 102 patients (22.3%), respectively. For patients who ingested tropatepine alone (n = 94), 29 (30.8%) showed agitation or delirium. A reported median ingested dose of 270 mg of tropatepine was associated with the onset of central and peripheral antimuscarinic signs, compared with 100 mg for peripheral signs alone (P = 0.0012). The median (IQR) duration of central antimuscarinic signs was 24 h (12-48 h). Agitation was treated by neostigmine and physostigmine in 25 and 13 patients, respectively. In 16 (76%) patients treated with neostigmine, there was no improvement in central signs, whereas 13 (100%) patients responded favorably to physostigmine. After adjustment for ingested dose, the complete resolution of central antimuscarinic signs was significantly higher in patients treated with physostigmine than with neostigmine (odds ratio 6.61; 95% CI: 1.00-44.94]; P = 0.0499).

Due to its long elimination half-life, tropatepine poisoning is frequently associated with a severe and prolonged antimuscarinic syndrome. Caring for these agitated patients requires substantial input from nursing staff.

Physostigmine is still little used but appears to be effective in controlling the central antimuscarinic syndrome induced by tropatepine.