GABAPENTIN AS A CONTROLLED SUBSTANCE

To advocate that the Drug Enforcement Administration classify gabapentin as a Schedule V substance due to its potential for abuse and patient harm.

Rationale

Gabapentin is a structural analog of gamma-aminobutyric acid that is approved by the Food and Drug Administration (FDA) for post-herpetic neuralgia and as an adjunctive therapy for partial seizures. Gabapentin has been identified as an opportunistic drug of abuse which, when used in conjunction with other medications, particularly opioids, may result in serious adverse events such as respiratory depression and even death. Gabapentin is used due to its low cost, classification as a noncontrolled substance, and increasing rates of on- and off-label prescribing attributable to clinicians’ desire for an alternative to opioids for pain management. In the U.S., gabapentin is and remains a noncontrolled substance at the federal level despite evidence suggestive of diversion and abuse with opioids. Most recently, several states have made an effort to combat the diversion and abuse of gabapentin by examining various regulatory approaches, such as reclassification of gabapentin as controlled substance or mandating the reporting of the prescribing and/or dispensing of gabapentin to a state-level prescription drug monitoring program (PDMPs). This fragmented geographic approach yields only a modest benefit in combating abuse and the national opioid epidemic. Hence, federal-level reclassification of gabapentin as controlled substance and implementation of national pharmacovigilance is warranted. As recently as April 2019, the United Kingdom reclassified gabapentin as a Class C controlled substance, which required similar dispensing and monitoring as controlled substances in the U.S., due to the increase in abuse they have seen in this drug.

As defined by the Drug Enforcement Administration (DEA), Schedule V controlled substances “are defined as drugs with lower potential for abuse than Schedule IV” substances. Schedule IV substances “are defined as drugs with a low potential for abuse and low risk of dependence.” Recent data from multiple sources have shown a significant increase in gabapentin misuse, abuse, and diversion over the past 10 years, and one study found that 22% of a sample of 162 opioid-dependent patients had a prescription for gabapentin, of which 40% indicated they used more than prescribed to augment and enhance their opioid experiences. Illicit use of gabapentin has increased drug diversion and fatality rates, as indicated by data from the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS) system and American Association of Poison Control Centers (AAPCC), respectively.

The criteria used by DEA to determine whether to control or reschedule a drug include (a) the drug’s actual or relative potential for abuse; (b) scientific evidence of its pharmacological effect, if known; (c) the state of current scientific knowledge regarding the abuse of the drug or other substance; (d) its history or current pattern of abuse; (e) the scope, duration, and significance of abuse; (f) what, if any, risk there is to public health; (g) its psychic or physiological dependence liability; and (e) whether the substance is a precursor of a substance already controlled under the law. Based on an assessment using these criteria, gabapentin is similar to other controlled substances found in Schedule V and should therefore be assigned to Schedule V. Additionally, gabapentin closely resembles pregabalin, a schedule V drug under the Controlled Substances Act in its chemical structure and pharmacological activity. Because some states have already taken steps to reschedule gabapentin as Schedule V or have added it to their PDMPs, the DEA should take steps to change the schedule status of gabapentin to ensure continuity of care and monitoring.

While it is difficult to predict the impact rescheduling may have on abuse, the current extent of abuse is likely exacerbated by easy access to and excessive supply of these therapies. However, the potential public health benefit of rescheduling must be weighed against concerns about restricting patients’ access to treatment and increasing administrative and other burdens on pharmacists and other clinicians. The proposed change to a more restrictive schedule would require stricter recordkeeping and security processes, which could in turn make providers reluctant to prescribe these therapies for patients who need pain management. In balancing these concerns, it should be noted that increased control of drugs with abuse potential is in the best interests of patients and public health. DEA and other stakeholders should monitor the impact of this scheduling change on patient access and practice, as well as monitor the impact of other strategies that have been implemented to minimize the abuse and diversion of these therapies.