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. 2022 Mar;88(3):1288-1297.
doi: 10.1111/bcp.15073. Epub 2021 Oct 8.

Pregabalin poisoning: Evaluation of dose-toxicity relationship

Saskia J Rietjens  1 , Maaike A Sikma  1   2 , Claudine C Hunault  1 , Dylan W de Lange  1   2 , Laura Hondebrink  1
Affiliations

Pregabalin poisoning: Evaluation of dose-toxicity relationship

Saskia J Rietjens et al. Br J Clin Pharmacol. 2022 Mar.

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.

Keywords: clinical toxicology; intoxication; overdose; poisoning; pregabalin; toxicity.

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Conflict of interest statement

The authors report no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Scatterplots depicting pregabalin dose (mg kg−1) (including median) in 34 patients stratified in two groups: “benign” (Poisoning Severity Score [PSS] none‐minor) and “significant toxicity” (PSS moderate‐severe). Black data points: cases from the prospective Dutch Poisons Information Center (DPIC) study. Grey data points: cases from literature. #, outlier
See this image and copyright information in PMC

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