Gabapentin use, abuse, and the US opioid epidemic: the case for reclassification as a controlled substance and the need for pharmacovigilance

Abstract

The abuse potential of gabapentin is well documented; with gabapentin having been noted as an agent highly sought after for use in potentiating opioids. When combined with opioids, the risk of respiratory depression and opioid-related mortality increases significantly. In the US, gabapentin was approved by the Food and Drug Administration as a non-controlled substance. To date, and in spite of empirical evidence suggestive of diversion and abuse with opioids, gabapentin remains a non-controlled substance at the federal level. This has forced individual US states and jurisdictions – often significantly impacted by the opioid epidemic – to forge ahead with legislative initiatives designed to reclassify and/or monitor the use of gabapentin. Since August 1, 2016, 14 of 51 US states and jurisdictions have either implemented legislative mandates requiring pharmacovigilance programs, amended rules and regulations, are in the throes of crafting policy, or are in the midst of gathering additional data for decision making. This fragmented geographic approach yields only a modest benefit in combating the abuse of gabapentin and/or the national opioid epidemic. Herein, we report state-by-state efforts to enhance pharmacovigilance and call for a re-evaluation of the schedule status of gabapentin at the federal level, and design and implementation of a national pharmacovigilance program.

A case of gabapentin overdose induced rhabdomyolysis requiring renal replacement therapy

“…Appropriate dosing adjustments should be made in patients receiving gabapentin in case of renal insufficiency. On the hand, our case reinforced the policy that gabapentin be the schedule V controlled substances in more and more states . Prescribers should be aware of high‐risk population and monitor for signs of abuse.…”

“…Gabapentin was originally approved by the US Food and Drug Administration (FDA) in 1993 for epilepsy and later, postherpetic neuralgia . Recently, gabapentin has been increasingly used in some off‐label indications as a desired alternative of opioids for pain management, probably due to its relative low rate of adverse effect and low cost. However, in recent years, reports of recreational gabapentin abuse or intentional misuse have increased at an alarming rate with reported adverse effects .…”

“…On the hand, our case reinforced the policy that gabapentin be the schedule V controlled substances in more and more states. 3 Prescribers should be aware of high-risk population and monitor for signs of abuse.…”

Need for international classification of gabapentin as a controlled substance

“…Recent international findings indicate that misuse of gabapentin in concert with opioids is a substantial threat to public health 3456789101112. There is an immediate need for international harmonisation of the classification of gabapentin as a controlled substance in light of known misuse potential 13. The US Food and Drug Administration has emphasised the need for programmatic pharmacovigilance of gapapentin prescribing,15 but such an effort has yet to be crafted 1314…”

“…Given the shift in regulation in the UK,1 we call for hastened re-evaluation of the non-schedule status of gabapentin in the US and the necessity of establishing a programmatic pharmacovigilance protocol at the federal level 1316. By mandating the incorporation of gabapentin into prescription drug monitoring programmes in the US, we could potentially mitigate the known levels of gabapentin misuse10 that may be adversely affecting the opioid epidemic 3…”