Gabapentin and Pregabalin: Is Their Abuse on the Rise?

Neurontin has much higher abuse potential than previously thought

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For years, physicians viewed gabapentin (Neurontin) and pregabalin (Lyrica) as drugs with little or no abuse potential. However, an emerging body of research suggests that these drugs are often misused and abused.

In a May 2017 study published in Pharmacoepidemiology and Drug Safety, Buttram and co-authors highlight a disturbing new trend. There's been an increase in gabapentin diversion, and this diversion is related to the opioid epidemic which is ravaging many parts of the United States.

People are getting high on a combination of gabapentin and prescription opioids (e.g., hydrocodone and oxycodone).

The authors of the study note the following:

Qualitative data suggest that gabapentin is being misused in conjunction with prescription opioids and that gabapentin and heroin are being combined and consumed together. Law enforcement reporters found these drug use trends to be contributing to gabapentin diversion.

What Are Gabapentin and Pregabalin?

When treating an ambit of chronic pain presentations and symptoms of discomfort, gabapentin (Neurontin) and pregabalin (Lyrica) are preferred medications among primary care physicians. These drugs are more effective at treating chronic pain than are ibuprofen or acetaminophen. Moreover, opioid dependence is an epidemic; thus, opioids like Norco or Vicodin are used only to treat acute and severe pain. In other words, Neurontin is stronger than something you would find in a drug store and less dangerous than opioids (heroin is a type of opioid).

How Do Gabapentin and Pregabalin Work?

Gabapentin was originally synthesized in 1977 as a GABA analogue. Nearly a decade later, pregabalin, a chemical cousin of gabapentin, was developed. Gabapentin was approved by the FDA in 1993. By 2004, pregabalin made it to market.

Gabapentin and pregabalin are collectively referred to as gabapentinoids and exert similar actions.

Although both developed to control seizures, these drugs have been recognized as effective pain neuromodulators and are often prescribed to ease various types of chronic pain and discomfort.

GABA, short for gamma-aminobutyric acid, is an inhibitory neurotransmitter, which is distributed throughout the cerebral cortex, or outer layer of the brain responsible for higher-brain function. GABA plays a role in various brain functions, including motor control and vision as well as the regulation of anxiety and pain.

Although originally intended to trip GABA receptors in the brain, the gabapentinoids don’t bind to GABA receptors. Furthermore, they don’t bind to cannabinoid, opioid, or benzodiazepine receptors either. Although the mechanism of these drugs has yet to be fully elucidated, it appears that these drugs exert antiseizure and pain-relief effects more circuitously. Nonetheless, the gabapentinoids do end up increasing GABA concentrations and decreasing glutamate concentrations in the brain.

Gabapentin and pregabalin share similar metabolic profiles, are both excreted by the kidneys, and don’t interact with other drugs (i.e., reduced risk of drug-drug interactions). One notable difference between these drugs is their bioavailability, or the amount of drug that actually makes it into circulation.

Specifically, pregabalin has higher bioavailabilty than does gabapentin and is more quickly absorbed and more potent. This difference has led some experts to hypothesize that pregabalin has higher abuse potential, and anecdotal accounts support this hypothesis. Nevertheless, when taken at sufficient dosages, both drugs are quick to act and effective, and both are abused and misused.

Clinical Uses of Gabapentin and Pregabalin

The gabapentinoids are similar to each other in their clinical effects.

Gabapentin tablets, capsules, and oral solutions are approved by the FDA to (1) treat partial seizures and (2) treat post-herpetic neuralgia, or shingles.

In Europe, gabapentin is approved for the treatment of neuropathic pain.

Pregabalin is approved by the FDA to treat (1) post-herpetic neuralgia, (2) diabetic peripheral neuropathy, (3) fibromyalgia, and (4) seizures. In Europe and Japan, pregabalin is approved to treat neuropathic pain and generalized anxiety disorder.

Gabapentin is not considered a controlled substance by the U.S. government, and the drug is safer than other anticonvulsants. This enviable safety profile has fueled off-label uses of gabapentin despite a dearth of clinical trials to support such uses.

Between 83 and 95 percent of gabapentin’s sales off-label. Here are some off-label uses of gabapentin:

  • alcohol, benzodiazepine, marijuana, and opioid withdrawal syndrome
  • attention deficit disorder
  • bipolar disorder
  • complex regional pain syndrome
  • diabetic neuropathy
  • hot flashes
  • migraine headaches
  • peripheral neuropathy
  • periodic limb movement disorder of sleep
  • restless legs syndrome
  • trigeminal neuralgia

Although the DEA classifies pregabalin as a Schedule V drug, indicating the lowest potential for abuse, it’s still a controlled substance. This fact coupled with the reality that Lyrica (pregabalin) is more expensive than Neurontin (gabapentin) likely explains why Neurontin is much more widely prescribed.

Finally, many physicians will prescribe gabapentin instead of pregabalin because gabapentin is much cheaper. Pregabalin is a very costly treatment. Because both medications have the same effects, it's more prudent to go with the cheaper option.

Gabapentin Abuse Explained

Substance misuse and substance abuse are different things, and the difference lies in intention.

According to the FDA:

“When a person takes a legal prescription medication for a purpose other than the reason it was prescribed, or when that person takes a drug not prescribed to him or her, that is misuse of a drug.”

Drug abuse is a special form of substance misuse. It happens when people take drugs to specifically get “high,” or experience a euphoric feeling. With respect to gabapentin and pregabalin, this euphoria has been described in different ways and is reminiscent of the effects of opioids, benzodiazepines, and psychedelics.

Lots of physicians prescribe gabapentin for all kinds of things, including pain, psychiatric conditions, and substance use disorders; many of these physicians probably don’t realize this drug’s potential for abuse. Because it is so widely dispensed in abundant quantities, and much cheaper and easier to prescribe than pregabalin—which is a controlled substance—gabapentin has become a more prevalent drug of abuse by people seeking out its quick euphoric highs. Furthermore, people who have substance use disorders and psychiatric illness are most likely to abuse these drugs. In other words, gabapentin is often prescribed to people who exhibit higher frequency of abuse. 

Not everybody who abuses gabapentin—and less frequently pregabalin—have prescriptions for these medications. Diversion is big business for drug dealers, and these drugs inevitably make their way to the streets. Only between 40 and 65 percent of people who misuse and abuse gabapentin have prescriptions for the drug.

A 2012 report estimated that prescription of pregabalin and gabapentin had increased by 350 percent and 150 percent, respectively, over a previous five-year period.

Of note, some people who are prescribed gabapentin simply misuse the drug in an attempt to self-treat symptoms. Some people also misuse the drug as a means of self-harm. Moreover, people abuse the drug while abusing other things, like opioids, alcohol and benzodiazepines.

In 2010, the first study was published indicating the risk of pregabalin abuse. Subsequently, the European Union added this drug to its list of recreational psychoactive substances. Between 2010 and 2016, about two dozen studies have been examining the abuse potential of gabapentin and pregabalin.

Here are some more specific facts related to gabapentin and pregabalin abuse and misuse. These findings are derived from recent studies.

  • One study suggests that the frequency of gabapentin and pregabalin abuse among people living in the UK aged between 16 and 59 years is 1.1 percent and 0.5 percent, respectively. According to this study, the rate of cannabis abuse is 28.1 percent and cocaine abuse is 8.1 percent. In other words, in people without substance use disorders or psychiatric illness, rates of gabapentinoid abuse are lower than those of other more traditional drugs.
  • Among people with opioid disorders, the rates of gabapentin abuse were between 15 and 22 percent. Whereas, the rate of pregabalin abuse among members of this same population varied more widely: between 3 and 68 percent. Overall, people with substance use disorders seem to abuse gabapentinoids at rates similar to other traditional drugs.
  • Among Americans who misused opioids, the rate of gabapentin abuse was double that of amphetamine abuse and about equal to clonazepam (a type of benzodiazepine) misuse.
  • In Scotland, 22 percent of people who went to methadone clinics abused gabapentin.
  • A 2015 study identified the recreational abuse of gabapentin as rapidly increasing. Specifically, there was a 2950 percent increase in abuse from 2008.
  • National drug-utilization databases indicate that pregabalin is being prescribed at much higher dosages than recommended, which can lead to abuse.
  • Some studies suggest that those who abuse gabapentinoids tend to be young males (30-ish) and low-income. However, data regarding gender and abuse are conflicting.
  • Based on case report data "drawn from a quarterly survey of prescription drug diversion
    completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations," Buttram and colleagues found that the diversion rates raised from zero cases in the first two quarters of 2002 to a high of 0.027 cases per 100,000 people in the last quarter of 2015.
  • Diversion of gabapentin appears to be common In US prisons.

Effects Other Than Euphoria

In addition to euphoria, people who abuse gabapentinoids at supratherapeutic, or higher than recommended dosages, also describe other effects including the following:

  • contentment
  • relaxation
  • dissociation
  • improved sociability
  • empathy
  • uninhibited behavior
  • audio and visual hallucinations

Of note, these effects seem to vary based on tolerance and dose. Additionally, abrupt discontinuation of gabapentinoids can result in withdrawal suggestive of physical dependence. Moreover, people withdrawing from gabapentinoids can also experience intense mental cravings.

Risks of Gabapentinoid Overdose

When used as prescribed, gabapentin and pregabalin are pretty safe. Adverse effects tend to be mild and include drowsiness, somnolence, ataxia, dizziness, and fatigue.

Unlike other drugs of abuse, even when overdosed on, gabapentinoids still cause only mild effects, such as transient high blood pressure, increased heart rate and other adverse effects similar to those seen at therapeutic doses. Gabapentinoid overdose typically doesn’t require hospitalization and no fatalities from overdose have been reported. People who overdose usually return to baseline after about 10 hours of ingestion.

The Role That Physicians Play

It would be too easy and callous to place the blame for gabapentinoid abuse, misuse, and dependence squarely on the shoulders of prescribing physicians. Sure, these medications are prescription-only and thus can invariably be traced back to physicians themselves; however, we must understand the unenviable position that providers are in when a patient complains of the intense pain and discomfort that accompanies chronic pain.

For instance, it’s common for patients with neuropathic and other types of chronic pain and discomfort to experience pain that would shock a person without the conditions. When a person comes into the physician’s office complaining of burning in their extremities, feelings of “walking on glass” and so forth, the physicians has little with which to treat these terrible symptoms, and gabapentin or pregabalin are often the only effective options.

Nevertheless, physicians should be on the lookout for signs that a patient is misusing or abusing these drugs or planning to engage in diversion including the following:

  • Patients with psychiatric or substance use disorders should be closely monitored for abuse or diversion.
  • Indications of abuse include the patient asking for Neurontin or Lyrica specifically, for higher doses than prescribed, or for multiple prescriptions during a short period of time.
  • Physicians should make sure that patients aren’t “doctor shopping” or receiving multiple prescriptions from multiple providers. A common excuse for such behavior is that the drugs were “lost” or “stolen.”
  • The physician should consider performing a urine drug screen (UDS) in patients suspected of diversion. If these patients are receiving prescriptions for gabapentinoids but these drugs aren’t detected in the urine, then these drugs are likely destined for the streets.

A Note From Verywell

Although on the rise, abuse of gabapentin and pregabalin still affects only a minority of patients, and mostly those who are predisposed to abuse, such as people with opioid dependence. Moreover, even in cases of overdose, the effects of these medications are typically mild and transient—a far cry from the repercussions of opioid, alcohol, and benzodiazepine dependence, or conditions that these drugs are often used to treat.

If you or a loved one takes these drugs for legitimate chronic pain or discomfort, and these drugs provide relief, then these drugs are being used as intended. However, to minimize your risk of abuse, it’s important that you are closely monitored by your physician and take these drugs only at the recommended dosages. Understanding how they work can help. Also, don’t take these drugs to get “high," don't mix these drugs with alcohol, benzodiazepines, opioids, or other drugs of abuse, and don't give or sell these drugs to others.

If you every have any questions about the prescription medications that you're taking—especially medications with abuse potential—please ask your physician. Your physician can take time to discuss the risks and benefits of any medication that you're prescribed. In addition, you can also ask your pharamacist about the medications that you're prescribed. As a patient, it's your right to be informed about the medications that you're taking.

Sources:

Combating Misuse and Abuse of Prescription Drugs: Q&A with Michael Klein, Ph.D. July 28, 2010. www.fda.gov.

Evoy KE, Morrison MD and Saklad SR. “Abuse and Misuse of Pregabalin and Gabapentin.” Drugs. 2016.

Mack A. Examination of the Evidence for Off-Label Use of Gabapentin. Journal of Managed Care Pharmacy. 2003; 9: 559-568.

Smith RV, Havens JR, and Walsh SL. “Gabapentin misuse, abuse and diversion: a systematic review.” Addiction. 2016; 111: 1160-1174.

Tcheremissine, OV, and Bestha DP. Gabapentin Abuse in a Patient With Comorbid Mood and Substance Use Disorders. Innovations in Clinical Neuroscience. 2016; 13: 13-14.

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