According to the National Institute
of Drug Abuse, there are more than 115 people dying from opioid overdoses every
day in the United States.1 However, opioids are not the only drugs
contributing to the staggering amount of overdose deaths. One drug in
particular whose usage has been on the rise is gabapentin. In 2017, gabapentin
was implicated in more than one-third of overdose deaths in Kentucky.2
Gabapentin was first approved by the FDA in January, 1994 as an antiepileptic
medication.3 Since then, its usage has skyrocketed. In 2015, there
were over 43 million prescriptions written for gabapentin, and it is currently
the seventh-most prescribed medication in the United States.4
 |
|
Figure 1: Gabapentin prescription rates (in
millions) between the years of 2004 and 2015.4
|
The
rise in gabapentin prescriptions is mainly due to the drug company Pfizer
promoting their brand-name gabapentin (Neurontin) to physicians for a plethora
of off-label uses. Due to this mass-marketing, gabapentin is now prescribed not
only for epilepsy, but for anxiety, trigeminal neuralgia, restless legs
syndrome, diabetic neuropathy, migraines, insomnia, bipolar disorder, and many
other conditions.5 Some
analysts have stated that “up to 90 percent of Neurontin prescriptions were for
off-label uses.”6
Pfizer’s
mass-marketing campaign to physicians was so voracious that a felony case was
settled against them in 2004.6 According to the San Francisco
Chronicle, Pfizer “agreed to plead guilty to two felonies and pay $430 million
in penalties to settle charges
that it fraudulently promoted the drug Neurontin for a string of unapproved
uses.”6 Ironically, the FDA approved Neurontin to be sold as
generic gabapentin in the same year, making it more readily available and more
affordable. Coupled with the rise in prescriptions, gabapentin’s potential for
abuse has caused it to be added to the DEA’s list of controlled substances in
Kentucky, Ohio, and West Virginia in 2017.3
Gabapentin’s potential for abuse lies mainly
in its mechanism of action. Although its molecular structure closely resembles
the neurotransmitter GABA, it does not directly act on GABA receptors.7
Its proposed mechanism is that it mainly binds to voltage-gated calcium
channels on glutamatergic neurons.7 By closing the voltage-gated
calcium channels, less glutamate is released from presynaptic neurons,
therefore lowering the excitation level of the postsynaptic neurons. This
contributes to gabapentin’s perceived analgesic or anxiolytic/sedative effects.
Although
gabapentin has shown some efficacy in treating conditions like epilepsy, its
off-label usage is unlike any other medication on the market today. Even after
debunking many of its off-label uses and being placed on the DEA’s controlled
substances list in 3 states, gabapentin prescriptions are still being given out
at an alarming rate. Gabapentin’s contribution to drug overdoses should not be
overlooked, especially with the opioid epidemic the U.S. is currently
experiencing. Instead of being a first-line course of action, both physicians
and patients should question the efficacy of gabapentin before beginning treatment.
References:
1. National Institute on Drug
Abuse. (2018, March 06). Opioid Overdose Crisis. Retrieved from https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis
2. Gabapentin Abuse. (n.d.).
Retrieved from
https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2018/05/10/abuse-of-opioid-alternative-gabapentin-is-on-the-rise
3. Honarmand, A., Safavi, M., &
Zare, M. (2011). Gabapentin: An update of its pharmacological properties and
therapeutic use in epilepsy. Journal of
Research in Medical Sciences, 16(8), 1062-1069.
4. (n.d.). Retrieved from
https://www.addictionpro.com/article/prescription-drug-abuse/states-eye-adding-gabapentin-controlled-substance-list
5. Fukada, C., Kohler, J., Boon,
H., Austin, Z., & Krahn, M. (2012). Prescribing gabapentin off label:
Perspectives from psychiatry, pain and neurology specialists. Canadian Pharmacists Journal, 145(6),
280-284.
6. Tansey, B. (2012, January 28).
Huge penalty in drug fraud / Pfizer settles felony case in Neurontin off-label
promotion. Retrieved from
https://www.sfgate.com/business/article/Huge-penalty-in-drug-fraud-Pfizer-settles-2759293.php
7. Taylor, C. P. (1997). Mechanisms
of action of gabapentin. Revue
Neurologique, 153(1), 39-45.
By Hart Foley, Master of Medical
Sciences Student, University of Kentucky
I found it to be so crazy that gabapentin was initially approved for antiepileptic medication but, is being prescribed for so many other conditions. When looking at Figure 1, I am surprised that the usage did not skyrocket even earlier, since it was approved by the FDA way back in 1994.
ReplyDeleteMy small project in the Masters program actually has to do with neuropathic pain in the trigeminal neuralgia and trying to find an alternative, effective treatment by shifting focus onto non-addictive pain medications. One example of this are nonsteroidal anti-inflammatory drugs (NSAID’s).
Pain is caused by prostaglandins, which are produced by two enzymes, COX-1 and COX-2 (Asher, 2017). Researchers have found that COX-2 is the enzyme that releases prostaglandins which are specifically responsible for pain and inflammation (Asher, 2017). Unlike most NSAID’s, a COX-2 inhibitor will just suppress COX-2, unlike the others that inhibit both COX-1 and COX-2 (Asher, 2017). Pfizer’s Celebrex (generic name celecoxib), is the only drug that is left on the U.S. market (Asher, 2017). The problem that researchers are currently having are the severe risks that are accompanied with COX-2 inhibitors, such as an increase in a patient’s risk of a heart attack or stroke (Asher, 2017).
Hopefully in the near future, we will come up with a COX-2 inhibitor that can be used to treat chronic pain, and not have these adverse side effects. Once this discovery is made, the primary goal should be to completely change the treatment plan for severe pain from Opioids to NSAID’s, specifically COX-2 inhibitors.
Reference: Asher A, CPT. Celebrex, Vioxx, Bextra vs Opioids for Back or Neck Pain. Back & Neck Pain Treatment. https://www.verywellhealth.com/cox-2-inhibitors-compared-with-opioids-297303. Published February 14, 2017. Accessed October 26, 2018.
The concept of using drugs for other non-label ailments and conditions is an interesting topic – I found an article from 2010 discussing new uses for older drugs1, one of them being gabapentin.
ReplyDeleteThere are multiple aspects of this particular area of pharmacology – things that come to mind include: what is the mechanism of the drug? And how does this impact the diseases it can potentially treat? How do other effects/uses of the drug initially get discovered? Who is benefitting from the wide-spectrum use of the drug?
While Hart already described gabapentin’s mechanism of action, its target is utilized in illnesses other than its original creation. The article analyzes two different studies of gabapentin, one to treat restless leg syndrome and the other treating dancing eye syndrome1. Mixed results were reported; while it was found to have a positive impact on using gabapentin under these circumstances, there are several factors to consider. The studies were small-scale and could be considered difficult to apply to real world scenarios (with larger study populations, the data may become insignificant)1. Since gabapentin is a controlled substance that can have adverse side effects, there’s a benefit versus risk balance in assessing the use of the drug for various diseases.
What I find to be an especially intriguing factor is the controversary surrounding Pfizer’s settlement for marketing misleading information about the unapproved uses of the drug. I can see how it greatly benefits the pharmaceutical companies to be able to sell their drug to a wider audience with many different conditions – there’s an obvious connection between the claimed uses of gabapentin, its high rate of prescription, and the money-making aspect of the business. The article addresses this concern by noting, “Because gabapentin has been used for so many indications, concerns remain that pharmaceutical companies are simply trying to find new potential revenue markets for their older drugs.”1
This is an area that needs to be further researched – it has the capability of largely impacting our healthcare system and economy. The future of these drugs and their applications is unpredictable and ever-changing.
(2010). New uses for older drugs: the tales of aspirin, thalidomide, and gabapentin. Mayo Clinic proceedings, 85(6), 508-11.
I found this topic to be very interesting. I currently work at a pharmacy here in Lexington and I have noticed that gabapentin is one of the medications that is very common written for. However, I was unaware of the marketing campaign and court case that likely lead to the high prevalence of gabapentin use nation wide.
ReplyDeleteThe problem with gabapentin misuse seems to be particularly problematic in Kentucky. I found two studies conducted at the University of Kentucky that examined gabapentin misuse particularly in patients that use other drugs of abuse. One study calculated the prevalence of gabapentin in drug overdose post-mortem toxicology reports. Of the five jurisdictions that were studied, Kentucky was found to have the highest percentage of gabapentin-positive overdose deaths (41%). Overall, 21% of overdose decedents in all jurisdictions studied also tested positive for gabapentin.
A second study of 33 recent drug users in Appalachian Kentucky from existing cohorts examined their subjective experiences with using gabapentin. The study questions centered around themes such as initiation, motivations for continued use, and characteristics of misuse. While the participants' responses varied to some degree, most agreed that gabapentin use resulted in a "high", that it could cause withdrawal symptoms, and that one can build a tolerance to the drug.
The article also includes interesting quotes from some participants that you should read if you have a chance.
Clearly, there is evidence of a strong connection between opioids (and other drugs of abuse) and gabapentin. Additionally, although it was thought that gabapentin displayed no addictive proprieties, more and more studies are showing that this may not be the case. Kentucky has already taken one step to tackle this issue by categorizing gabapentin as Schedule 5 controlled substance and placing more restrictions on its use. I believe that prescribers particularly, as well as pharmacists, need to be more aware of how people are using this drug and the possible consequences it may have.
References:
Slavova, S., Miller, A., Bunn, T. L., White, J. R., Kirschke, D., Light, T., . . . Winecker, R. (2018). Prevalence of gabapentin in drug overdose postmortem toxicology testing results. Drug and Alcohol Dependence, 186, 80-85. doi:10.1016/j.drugalcdep.2018.01.018
Smith, R. V., Boland, E. M., Young, A. M., Lofwall, M. R., Quiroz, A., Staton, M., & Havens, J. R. (2018). A qualitative analysis of gabapentin misuse and diversion among people who use drugs in Appalachian Kentucky. Psychology of Addictive Behaviors, 32(1), 115-121. doi:10.1037/adb0000337
It is very alarming that up to 90% of current gabapentin prescriptions are used for off-label conditions. Recent review in the Substance Abuse: Review and Treatment by Peckman et al. finds that, Most of the evidence for off-label use is limited to a few small, low-quality studies. But higher quality evidence which indicates gabapentin non-efficacy is often lost in the shuffle. The review also finds that patients who where chronic users of gabapentin were significantly more likely to experience inpatient hospital stays or emergency department visits for altered mental status or respiratory depression. There are mounting reports of recreational or intentional misuse of gabapentin. What’s more alarming is that many of the prescribers are often unaware of gabapentin’s approved indications. They tendency to prescribe is largely guided by informal discussion with colleagues or professional meetings. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important for prescribers to realize the associated risks and weigh the risks with the potential benefits. Like Hart aptly mentioned, clinicians should exercise caution and practice evidence based medicine when prescribing any medication with potential for abuse or high risk profile.
ReplyDeleteReferences:
Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern?
Peckham, A. M., Evoy, K. E., Ochs, L., & Covvey, J. R. (2018). Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern?. Substance abuse : research and treatment, 12, 1178221818801311. doi:10.1177/1178221818801311
This comment has been removed by the author.
ReplyDeleteTalking about overdose & drug abuse, the other class that is always abused is the steroid based skin ointments & antihistamines. People are so scared of getting allergies & being sick, that they would go antihistamine abuse. almost same scenario with the steroid based skin ointment. People prefer immediate ailment rather than long systematic treatments.
ReplyDeleteSome studies show that gabapentin can induce euphoric effects. So there is every chance of it to become a replacement choice for opioids.
Small Study Reports Troubling Abuse Potential for Gabapentin.
https://www.uspharmacist.com/article/small-study-reports-troubling-abuse-potential-for-gabapentin
Through working in a pharmacy, I noticed just how often Gabapentin was prescribed. Reading this blog and seeing just how many overdoses happen every year heightened my curiosity on the insane usage rate that Neurontin currently sees. A blog I looked at showed that misuse rates of Gabapentin are extremely high. The study states that 40-65% of individuals with prescriptions for Gabapentin did not take as prescribed.1 The review I looked at showed that individuals with a history of substance abuse were much more likely to abuse Gabapentin. Patients said their reasons for abusing Gabapentin was that it was reminiscent of opioids. Many used Gabapentin recreationally, as the drug gave them a heightened sense of self. 1 A big reason that I believe Gabapentin can be misused so easily is the cost, costing just over 20$ for 270 capsules with a discount card. Insurance more often than not knocks this copay down to 0.
ReplyDeleteI think it was extremely smart for states like Kentucky to add it to the controlled substances list. This is a step in the right direction, and hopefully the FDA investigates and makes it controlled nationwide to help reduce the overdose risk we are currently facing. Physicians need to have limits on how much they are able to prescribe to discourage misuse.
Reference:
Smith, R. V., Havens, J. R., & Walsh, S. L. (2016). Gabapentin misuse, abuse and diversion: a systematic review. Addiction (Abingdon, England), 111(7), 1160-74.
I think it's appalling that individuals are suffering from this overprescription and this pharmaceutical company stays cashing in on their misfortune. Not only has Pfizer received lawsuits against Neurontin and Celebrex, but also Bextra (which was taken off the market), Chantix, Effexor, and Zoloft. The latter two have been linked to birth defects ("Pfizer," n.d.). Instances like these point out a big ethical issue of the drug industry, when pharmaceutical giants' only concern is money.
ReplyDeleteInterestingly enough, when I googled Pfizer, the first suggestion was "Pfizer gabapentin coupon."
With studies showing gabapentin's potential for abuse and such high prescription rates, it is no wonder that its use is becoming a phenomenon. In addition to its off-label purposes, gabapentin is used to treat alcohol and cocaine withdrawal. This seems like a way to gloss over a problem instead of actually taking care of it. Combined with other medications like opioids or anti-anxiety drugs, gabapentin is said to produce euphoria, similar to a high like that of marijuana. In addition to increasing restrictions on the drug, Ohio and West Virginia have been tracking prescriptions (Richardson, 2017). Hopefully stricter regulations can help to decrease lawsuits, abuse, and most importantly, overdoses.
Pfizer. (n.d.). Retrieved from https://www.drugdangers.com/manufacturers/pfizer/
Richardson, E. (2017, December 18). Is Gabapentin Abuse on the Rise? Retrieved from https://oceanbreezerecovery.org/blog/gabapentin-abuse/#comments
Being from a region plagued with opioid dependency and overdose, I have heard numerous accounts of opioid abusers using Gabapentin in conjunction with their preferred opioid as well. In fact, according to a nurse in my family who has dealt with numerous cases of drug abuse, Gabapentin is not commonly used by itself. Rather, it is almost always used with opioids. The reasoning for this, as described by an avid user, is that the anti-excitatory effects of the Gabapentin allow for a stronger effect of the opioid. This can also be seen in a study where the two are used in conjunction to treat cancer patients' pain. The study says that the ability of Gabapentin to decrease hyperexcitation along with that analgesic effects of the opioids may help to decrease the nociceptive response that leads to the perception of pain within these patients (Keskinbora et. al, 2007). It is a sad truth that there will always be the next drug for users to use. However, there may be hope with the development of AT-121, which I talked about in my blog. There may be future treatments using Gabapentin and that!
ReplyDeleteReference:
Keskinbora, K., Pekel, A. F. & Aydinli, I. (2007). Gabapentin and an Opioid Combination Versus Opioid Alone for the Management of Neuropathic Cancer Pain: A Randomized Open Trial. Jounal of Pain and Symptom Management, 34(2): 183-189
While working as a pharmacy tech, I learned of the recent rave for Gabapentin. This drug has always been so interesting to me due to it's many usages. It is crazy to me that it's uses range anywhere from an anti-epileptic to treating pain in even animals. It is wonderful that we have such a flexible drug but there are also the consequences that come along with a drug such as this one. As many of my peers have already addressed, the opioid epidemic is on the rise and gabapentin is one of the culprits. I found it interesting that when it was first approved in 1993, there was little to no worry about potential misuse of the drug. According to a recent discovery from a coroner's office in Louisville, gabapentin was found in 1/4th of overdose victims. Now, it is found in 1 out of every 3 overdoses. However, gabapentin alone is likely not the cause of death or fatal overdoses. It is when it is combined with opioid drugs like fentanyl or heroin that the drug helps to elicit a dangerous, maybe fatal, high. Those prescribed to these kinds of drugs should be routinely drug tested for opioid use to prevent this kind of drug combination from occurring. When used correctly, Gabapentin can be extremely helpful to those who need it. However, the opioid epidemic is creating a barrier to those who need it due to it's misuse. An addict will always find ways of "scoring" the drug of their liking or, if they can't, they will likely find an alternative to that drug. Hopefully, there will be new strategies to prescribing and patrolling the use of Gabapentin so that this drug can continue to help those in need.
ReplyDeletehttps://www.healthline.com/health-news/gabapentin-latest-pain-medication-in-opioid-overdoses#4
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