Pregabalin poisoning: Evaluation of dose-toxicity relationship

Abstract

Context: Pregabalin poisoning is mostly benign, although coma and convulsions occasionally occur. Aim: To determine the dose-toxicity relationship of pregabalin. Methods: Dose-toxicity data of isolated pregabalin poisonings were collected from (1) a prospective study performed by the Dutch Poisons Information Centre (4 April 2014 to 4 October 2016) and from (2) case reports and case series reported in literature. Poisonings were graded using the Poisoning Severity Score (PSS) and the relationship between dose (mg kg−1) and PSS was evaluated. Results: In our study (n = 21 patients), the most commonly observed symptoms were drowsiness (62%), confusion (29%) and apathy (24%). PSS was none in three (14%), minor in 15 (71%), and moderate in three patients (14%). Most case series also reported a PSS of none to minor in the majority of poisonings (69-100%). For 34 individual patients (21 from our study and 13 from literature), detailed data on dose and clinical course were available to examine the dose-toxicity relationship. The median dose was significantly lower in the PSS none-minor group (“benign”) (8.6 mg kg−1, interquartile range (IQ25-75) 5.0-17.6 mg kg−1) than in the PSS moderate-severe group (“significant toxicity”) (46.7 mg kg−1, IQ25-75 21.3-64.3 mg kg−1); estimate of the median difference = 27.3 mg kg−1 (95% confidence interval (CI): 10-48.6). Conclusions: In general, higher pregabalin doses result in more severe poisonings. Below 20 mg kg−1 the majority of patients (83%) only suffer from mild poisoning. However, large interindividual differences exist in pregabalin-induced toxicity. Therefore, pre-hospital triage should not only include pregabalin dose, but also underlying illnesses, co-exposures and reported symptoms.