Shane Darke1, Johan Duflou1,2, Amy Peacock1, Michael Farrell1, Julia Lappin1,3. 1. National Drug & Alcohol Research Centre, University of New South Wales, Sydney, Australia. 2. Sydney Medical School, University of Sydney, Sydney, Australia. 3. School of Psychiatry, University of New South Wales, Sydney, Australia.
Abstract
INTRODUCTION: Gabapentinoids are centrally active GABA agonists whose use has increased substantially in the past decade. The current study aimed to provide a comprehensive clinical profile of a national case series of fatal poisonings related to gabapentinoids. METHODS: Retrospective study of all deaths due to drug toxicity in Australia in which gabapentinoids were a contributory mechanism, retrieved from the National Coronial Information System (2000-2020). Information was collected on case characteristics, toxicology and major organ pathology. RESULTS: A total of 887 cases were identified, with a mean age of 45.7 years and 55.2% being male. Death was due to accidental toxicity in 81.3% of cases and intentional in 18.7%. Pre-existing disease was co-contributory to drug toxicity in 19.5%. Pregabalin was present in 92.9% of cases, with a median blood concentration of 7.6 mg/L (range 0.1-850.0 mg/L). Gabapentin was present in 7.2%, with a median blood concentration of 9.5 mg/L (range 0.5-1940.0 mg/L). Both pregabalin and gabapentin were present in five cases. No other gabapentinoids were detected. Drugs other than gabapentinoids were present in 99.8%, most frequently opioids (90.1%), hypnosedatives (76.9%) and antidepressants (60.5%). A body mass index in the obese range was seen in 45.4%. Clinically significant pre-existing disease was common, notably cardiomegaly (24.9%), emphysema (20.2%), nephrosclerosis (18.7%) and severe hepatic steatosis (11.7%). CONCLUSIONS: The concomitant use of other drugs was close to universal, with CNS depressants predominating. Mental health problems, chronic pain and substance misuse were prominent.
INTRODUCTION: Gabapentinoids are centrally active GABA agonists whose use has increased substantially in the past decade. The current study aimed to provide a comprehensive clinical profile of a national case series of fatal poisonings related to gabapentinoids. METHODS: Retrospective study of all deaths due to drug toxicity in Australia in which gabapentinoids were a contributory mechanism, retrieved from the National Coronial Information System (2000-2020). Information was collected on case characteristics, toxicology and major organ pathology. RESULTS: A total of 887 cases were identified, with a mean age of 45.7 years and 55.2% being male. Death was due to accidental toxicity in 81.3% of cases and intentional in 18.7%. Pre-existing disease was co-contributory to drug toxicity in 19.5%. Pregabalin was present in 92.9% of cases, with a median blood concentration of 7.6 mg/L (range 0.1-850.0 mg/L). Gabapentin was present in 7.2%, with a median blood concentration of 9.5 mg/L (range 0.5-1940.0 mg/L). Both pregabalin and gabapentin were present in five cases. No other gabapentinoids were detected. Drugs other than gabapentinoids were present in 99.8%, most frequently opioids (90.1%), hypnosedatives (76.9%) and antidepressants (60.5%). A body mass index in the obese range was seen in 45.4%. Clinically significant pre-existing disease was common, notably cardiomegaly (24.9%), emphysema (20.2%), nephrosclerosis (18.7%) and severe hepatic steatosis (11.7%). CONCLUSIONS: The concomitant use of other drugs was close to universal, with CNS depressants predominating. Mental health problems, chronic pain and substance misuse were prominent.