Ask the Expert: June 2015
By McKenzie C. Ferguson, PharmD, BCPS and Breanna Wyman, PharmD
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Q: Why is there abuse of gabapentin?
A: Gabapentin (Gralise, Neurontin) is a widely prescribed drug used for the management of a number of neuropathic pain syndromes.
The agent is FDA-approved for the treatment of postherpetic neuralgia as well as for adjunctive treatment of epilepsy. Although it is not a Drug Enforcement Administration-scheduled drug, reports of gabapentin abuse warrant prescriber consideration.
Post-marketing reports have described symptoms of agitation, confusion, and disorientation upon abrupt withdrawal of gabapentin. Cases usually involve other potentiating factors, such as the use of higher than recommended doses for unapproved indications, a history of poly-substance abuse, or the use of gabapentin to relieve symptoms of withdrawal from other substances.1
These factors also have been identified in reports of gabapentin misuse. One case report describes a 67-year-old woman with a history of mood disorders and alcohol abuse receiving gabapentin following a diagnosis of polyneuritis. She was taking at least 7,200 mg daily, twice the prescribed amount, and exhibiting aberrant drug-related behaviors, such as exaggerating symptoms to get prescriptions and asking pharmacies to give her gabapentin without a prescription. When denied her prescription, she developed withdrawal symptoms including trembling, sweating, excitation, pallor, and exophthalmia and was hospitalized.2
In a case series with similar features, 2 patients with a history of alcohol dependence were taking at least twice the prescribed dose of gabapentin for several months. Taking a daily dose of 3,600 mg, one patient cited reduced alcohol cravings and feeling calmer. After stopping gabapentin, both patients experienced a similar tremulous, agitated, and tachycardic state. Despite treatment that included lorazepam, symptoms did not significantly improve until gabapentin was resumed.3
Interestingly, gabapentin has been studied as a treatment for alcohol dependence. In a randomized, placebo-controlled trial, gabapentin (900 or 1800 mg/d) improved abstinence rates and reduced symptoms of insomnia, dysphoria, and cravings in the treatment of alcohol dependence. The higher dose was most effective at achieving abstinence and symptom control. Gabapentin at both dosages was well-tolerated and no significant differences were noted between groups in type, number or severity of adverse events.4
Correctional institutions in Florida noticed a pattern of aberrant behaviors (eg, requesting refills too soon) among inmates taking gabapentin for psychiatric and/or medical conditions. Five inmates with a history of cocaine abuse prior to imprisonment disclosed the occurrence of widespread gabapentin abuse. Capsules were being opened and the powder snorted, with some inmates reporting an altered mental state or “high” associated with this act, similar to that derived from snorting cocaine. The inmates denied abuse of other psychotropic medications. No adverse effects were reported as a result of gabapentin abuse.
After this finding, steps were taken to lessen abuse by removing gabapentin capsules from the formulary and dispensing only single-dose tablets when justified by medical necessity. No inmates reported withdrawal symptoms associated with cocaine dependence because the average time of incarceration had been over 2 years.5
This distinction is important because gabapentin also has been studied in the management of cocaine dependence. In an open-label, non-controlled study, 30 patients were initiated on gabapentin and titrated up to 600 mg twice daily. At weekly visits for the duration of the 8-week study, a urine sample was collected and patients were asked to self-
report cocaine use and rate cravings on a visual analog scale. Gabapentin significantly reduced the amount and frequency of cravings as well as the percentage of positive urine drug screens (86% vs 29%) from baseline values. Although the dropout rate was high, there were no adverse effects associated with treatment.6 However, these results are not conclusively supported. A randomized, placebo-controlled trial found no difference between gabapentin and placebo in achieving abstinence or reducing cravings in cocaine dependence.7
Another study investigating the occurrence of gabapentin abuse in a substance misuse population distributed a questionnaire at 6 substance misuse clinics.8 The questionnaire was used to detect gabapentinoid (pregabalin [Lyrica], a Schedule V controlled substance, or gabapentin) abuse and encompassed both prescription and non-prescription use. According to the Lyrica Package Insert: “Lyrica is not known to be active at receptor sites associated with drugs of abuse. As with any central nervous system active drug, carefully evaluate patients for history of drug abuse and observe them for signs of Lyrica misuse or abuse (eg, development of tolerance, dose escalation, drug-seeking behavior).”9
Of the 129 returned questionnaires, 11 patients were being prescribed gabapentinoids and 29 patients were using gabapentinoids despite not having a prescription. All 29 of those using gabapentinoids without a prescription also were receiving methadone treatment for opioid dependency. When prompted to give a reason for non-prescribed gabapentinoid use, all responses could be assigned to the category “used to become intoxicated” (22/29) and/or “used to potentiate the effects of methadone” (11/29).8
In a study of postmortem toxicology conducted over a 2-year period in Finland, cases that tested positive for gabapentin or pregabalin were included to determine if abuse of these drugs contributed to the fatalities. Death certificates and pathology reports were reviewed for each individual case to determine if the pregabalin or gabapentin detected in the analysis was attributable to medical use or abuse. For a case to be classified as an abuse case, the deceased had to be a known drug abuser, have injection marks or equipment found near the body, have other illicit drugs on the toxicology report, or have detectable gabapentinoid without having a prescription for the drug. If pregabalin or gabapentin was the main toxicologic finding, they classified it as a poisoning.
Of the 13,766 cases investigated with toxicological analyses during the study period, 0.31% were positive for gabapentin. Of the gabapentin cases, 18.6% were considered abuse and 4.7% were poisonings. An overwhelming majority of abuse cases (87.5%) also involved opioid intoxication and 100% involved alcohol and/or opioids. In further study results, pregabalin was implicated in more postmortem cases than gabapentin (2.3% vs. 0.31%). In addition, a greater number of pregabalin cases were designated as abuse cases than gabapentin cases (48.1% vs. 18.6%, respectively).10 However, the abuse potential for gabapentin is nonetheless present in this study and should not be ignored.
Last updated on: September 14, 2015
Gabapentin is a medication that is structurally related to the inhibitory neurotransmitter GABA. It does not bind to the GABA receptors but instead modulates the release of excitatory neurotransmitters, which participate in nociception.
The medication has several off label uses as well such as migraine, hot flashes, fibromyalgia, and more. Adverse events associated with the drug include: jerky movements, loss of coordination, drowsiness, and dizziness. Higher doses can cause withdrawal symptoms such as seizures, suicidal ideation, and irritability.
Gabapentin is not scheduled as a controlled substance, meaning that the medication has little potential for addiction and abuse. However, the drug does show characteristics of various medications associated with misuse and addiction such as benzodiazepines, producing similar withdrawal syndromes and psychoactive effects.
According to the American Addiction Center, gabapentin has become a drug of abuse with users reporting effects such as euphoria, a marijuana-like high, and other users described their state after taking the medication to be zombie like.2 After hearing this information it led me to a discussion with a pharmacist that I work with prompting us to ask the question of whether or not gabapentin should have a schedule change.
What studies have been conducted?
Currently gabapentin is not scheduled as a controlled substance because when given as a monotherapy, it has very little abuse potential. However, when the drug is taken with other medications such as muscle relaxants, opioids, or various anxiety medications, gabapentin’s potential for abuse and addiction significantly increasing and ultimately gets those individuals high.3
Abusing gabapentin is not a recent affair and goes all the way back to 2004, the year that the generic was released. A study was conducted at a Florida correctional facility, which surveyed inmates receiving gabapentin. Out of 96 prescriptions, only 19 were actually in the hands of an inmate that was actually prescribed that drug. Inmates reported crushing and snorting the pills in order to get high similar to that of cocaine. After this study was performed, gabapentin was removed from various correctional facilities and was no longer allowed to be dispensed to inmates. In 2011, a significant increase in the number of individuals using gabapentin as a cutting agent in heroin was seen in a number of police reports across the country.
Another study examining the misuse and abuse of the drug gabapentin, obtained urine samples from a total of 323 patients who were being treated at various pain clinics and addiction centers found that 70 of those patients were taking Gabapentin without a prescription.
What’s going on currently?
As of December 1, 2016 the State of Ohio Board of Pharmacy requires all pharmacies, wholesalers, and physicians to submit the specified dispensing, personal furnishing, or wholesale sale information on all products containing gabapentin to the Ohio Automated Rx Reporting System.
What does this mean for the future?
Ohio has already acknowledged gabapentin as a drug of abuse that needs to be monitored and reported. As the number of individuals abusing gabapentin increases, more overdoses are being seen throughout the country along with an increased number of individuals enrolled into pain addiction clinics for gabapentin abuse. With this being said why is gabapentin still not seen as a controlled substance? What is your opinion on the matter?
1.American Pain Society's Principles of Analgesic Use in The Treatment of Acute Pain and Cancer Pain, 6th Edition, 2008.
2. American Addiction Centers, Gabapentin: Withdrawal Symptoms, Abuse & Use in Drug & Alcohol Dtox. American Addiction Centers website. http://americanaddictioncenters.org/addiction-medications/gabapentin/#treatment
3. Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. Br J GenPract. 2012; 62(601):406-407.
Shelby Leheny, Pharm D, B.S
Shelby Leheny received her Doctor of Pharmacy Degree from Lake Erie College of Osteopathic Medicine (LECOM) and her Bachelor's of Science degree at the University of Pittsburgh. She is a pharmacist at CVS.