Gabapentinoid Abuse in France: Evidence on Health Consequences and New Points of Vigilance

Abstract

Introduction: Gabapentinoid drugs (gabapentin and pregabalin) are widely used worldwide for epileptic and pain disorders. First signals of gabapentinoid abuse occurred in the last decade. This study aims to describe clinical characteristics of gabapentinoid use related disorders and health consequences in France.Materials and Methods: We designed a multisource investigation reviewing data reported to the French Addictovigilance Network (FAN) with pregabalin and gabapentin from 2010 to 2019. Information was obtained through the analysis of Spontaneous Reports (SRs) notified by health professionals and the pharmacoepidemiological surveys OSIAP (suspicious prescriptions forms indicators of potential abuse), OPPIDUM (observation of illicit drugs and misuse of psychotropic medications), DRAMES (death related to prescription drugs and other substances), and DTA (toxic deaths due to analgesics).Results: Over 2010–2019 period, were collected: (i) 265 SRs (258 pregabalin; 7 gabapentin); (ii) 816 forged prescription forms (805 pregabalin, 10 gabapentin, 1 involving both drugs); (iii) 145 cases of gabapentinoid use in people who use drugs (121 pregabalin; 24 gabapentin) and (iv) 31 cases of gabapentinoid-related deaths (25 pregabalin; 6 gabapentin). Risk factors of gabapentinoid abuse were opioid use disorders or psychiatric history, but cases of primary abuse in subjects without any substance abuse history were observed. Adverse outcomes concern almost exclusively pregabalin, with coma, dyspnea, convulsion, and conduction disorders. Treatment demands increased from 10.6% in 2018 to 23.1% in 2019, with pregabalin cited as the first substance leading to addictological care in the 2019 OPPIDUM survey. Gabapentinoid-related deaths increased over time. Pregabalin has become the first drug mentioned in forged prescriptions in 2019 (23.8% of OSIAP), while it ranked at the 15th position in 2017 (2.6%).Discussion: This study shows the importance of addictovigilance monitoring for gabapentinoids. Addictovigilance data helped to make visible the gabapentinoid-abuse related health harms (hospitalization for serious neurologic, psychiatric or cardiac effects, requests for addictological support and deaths) and to confirm the intrinsic abuse potential of pregabalin. These data highlight new points of vigilance considering observed primary abuse. At this point in France, the risk of abuse and related complications is very apparent with pregabalin. Still, it is identical to that observed elsewhere with gabapentin.

Non-medical Use of Prescription Gabapentinoids (Gabapentin and Pregabalin) in Five European Countries

“…When comparing the five European countries, those who non-medically use gabapentinoids were estimated to have a higher likelihood of chronic pain, use of illicit substances, and history of substance abuse treatment compared to the general population. These results are in concordance with country surveys, reviews and metanalyses published previously ( 8 , 23 , 24 ).…”

“…When evaluating the rates by drug, as described before, pregabalin has more endorsements than gabapentin, for example, in a recent paper describing data from addictovigilance monitoring for gabapentinoids ( 24 ). Some publications have described a higher abuse liability for pregabalin compared to gabapentin.…”

“…The main reason for non-medical use was in both medications for self-treat any pain, followed to treat other medical conditions; few respondents used them to get high or to come down; also, there were a percentage of people using them to prevent withdrawal symptoms. Another article, based on data of pharmavigilance ( 24 ), found that the use of pregabalin was not only related to the objective to get high, but also, to prevent withdrawal symptoms, as a substitute of other substances and to potentiate the effect of other drugs (mainly benzodiazepines and opioids). In our sample, the inhaled and intravenous route were mainly reported for those who use pregabalin and gabapentin to prevent withdrawal syndrome, to come down and to get high.…”

“…When prescribing these medications it is important to be aware and monitor for signs of misuse and overdosification, mainly in patients with risk factors for NMU (previous history of substance use disorder and chronic pain). It is important to remark that, although NMU of gabapentinoids is more frequent in patients with previous substance use disorder, there are described cases of a primary abuse in people without any of the known risk factors ( 24 ), for this reason, it is important to monitor for signs of NMU in all patients in treatment with gabapentinoids. The detection of NMU could be complicated as these medications are not detected in routine toxicology urine controls.…”

“…Some studies have tried to analyze the possible usefulness of pregabalin and gabapentin in the treatment of benzodiazepine use disorder, but there are no clear results regarding this (27,28). When evaluating the rates by drug, as described before, pregabalin has more endorsements than gabapentin, for example, in a recent paper describing data from addictovigilance monitoring for gabapentinoids (24). Some publications have described a higher abuse liability for pregabalin compared to gabapentin.…”