Pregabalin poisoning: Evaluation of dose‐toxicity relationship

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.