Genes May Explain Why Gabapentin Works for Some Pain Patients

By Pat Anson

Over the years, gabapentin (Neurontin) has been prescribed for dozens of health conditions, from epilepsy and fibromyalgia to depression and post-operative pain. It’s even been used to treat bipolar disorder. Gabapentin has been marketed for so many different conditions – at times illegally -- that a pharmaceutical company executive infamously referred to the drug as “snake oil.”

Even though it’s been approved for medical use for over 30 years, the UK’s National Health Service admits it’s still “not clear exactly how gabapentin works.”

A new study may finally help explain why gabapentin is an effective pain medication for some patients and an addictive drug with unwelcome side effects for many others.

It could be all in the genes.

Researchers at the University of Edinburgh took another look at a previous study of women with chronic pelvic pain to see why gabapentin worked no better than a placebo for most, but was a moderately effective pain reliever for about 40% of them.

Researchers took saliva samples from 71 women who participated in the study -- 29 who responded to gabapentin and 42 who had no improvement -- and found that the responders were more likely to have a variation of the gene Neuregulin 3 (NRG3). The gene is primarily expressed in the brain, spinal cord and central nervous system, and helps regulate pain sensation and transmission.

The findings, recently published in the journal iScience, may explain why gabapentin works for some women with chronic pelvic pain.

"A genetic factor that can predict how well gabapentin will work in patients offers the prospect of tailored treatment, and provides invaluable insights into understanding chronic pain. We hope eventually to use this genetic marker to optimize personalized treatment decisions and minimize adverse effects for women with chronic pelvic pain," wrote lead author Scott Mackenzie, MD, from the University of Edinburgh's Centre for Reproductive Health.

The study also has implications for other chronic pain conditions. Further research is needed to confirm the findings, but researchers say a genetic test for NRG3 could help limit the use of gabapentin to people who actually benefit from the drug.

"Isolating this single genetic marker is an important discovery that could ultimately help refine treatments for millions of women worldwide who suffer from chronic pelvic pain, as well as increasing our understanding of its role in other pain conditions. We believe this is an exciting opportunity for collaboration with a commercial partner who can help translate the research into a clinical setting," said Susan Bodie, PhD, Head of Business Development for the College of Medicine and Veterinary Medicine at the University of Edinburgh.

Gabapentin and other nerve drugs like pregabalin (Lyrica) have come under increased scrutiny in the UK because they are increasingly involved in overdose deaths.  

A recent analysis of drug tests suggests that gabapentin is also being misused in the U.S. Gabapentin was found in in over 13% of urine samples that tested positive for fentanyl -- about twice the number of drug tests in which prescription opioids were found.

Despite the risks of side effects and addiction, gabapentin is increasingly prescribed “off-label” for conditions it is not approved to treat, such as dental pain. A 2019 study found little evidence that gabapentin and pregabalin should be used for pain and said their effectiveness was often exaggerated by prescribing guidelines.

The CDC’s revised opioid guideline says gabapentin and pregabalin can have “small to moderate improvements” on pain, but with a moderate risk of side effects.

UK Crisis Grows Over Pregabalin Misuse

By Pat Anson, PNN Editor

Nearly 3,400 people in the UK have died from overdoses involving pregabalin in the last five years, according to an investigation by The Sunday Times.

One of them was a young man named Alex Cottam, who spiraled into drug abuse, addiction and a fatal overdose after he started taking pregabalin for anxiety and depression.   

“It’s hard to imagine somebody’s whole life revolved around a pill, but it did,” said Cottam’s mother, Michelle. “It completely changed him, like it was an obsession.”

The Sunday Times’ story about Cottam and other pregabalin users sparked a frenzy in British tabloids about the growing misuse of the drug.

“Our Pregabalin nightmare” was the headline in the Daily Mail, which shared the story of a woman with arthritis who said she “felt like I was losing my mind” after taking the drug for six months. Another woman told the tabloid she began seeing “dead people” within 30 minutes of her first dose.  

In a first-person account published in The Telegraph, Miranda Levy wrote about the severe withdrawal she experienced when she stopped taking pregabalin for depression.

“First came the pins and needles, closely followed by the sweating,” said Levy. “Add to this the progression of unremitting nausea, retching, diarrhea, jitteriness, dizziness so bad you can’t stand up and the feeling you’re about to die.”

Pregabalin – commonly known as the brand name Lyrica -- was never intended to treat anxiety, depression or arthritis. It was originally developed as an anticonvulsant that was first approved by the FDA in 2004 as a treatment for epilepsy. Since then it has been prescribed for dozens of painful conditions such as fibromyalgia and diabetic neuropathy, and is sometimes hailed as a “wonder drug” that is safer than opioids.

Pregabalin has helped some pain patients, but for many it’s also had severe side effects such as fatigue, insomnia and cognitive decline. Margaret Heath started taking pregabalin two years ago for Complex Regional Pain Syndrome (CRPS) and says it ruined her life.

"I've been on every type of morphine you can be put on... this is by far and away the worse drug to be on. It's worse than fentanyl. There is absolutely no comparison with the viciousness of the withdrawal of pregabalin," Heath told LBC News. "There would be days where I would not be able to do anything except lie there... it was debilitating."

Nearly nine million prescriptions for pregabalin were written in the US in 2021, the last year for which data is available. A similar number were written in England and Wales the following year, despite growing concerns in the UK that pregabalin is being misused to boost the euphoric effects of other drugs.

Pregabalin has become so popular with illicit drug users that it frequently appears in overdose toxicology reports. The number of fatal overdoses in the UK involving pregabalin has risen by nearly 11,000% since 2011, followed by a 3,275% increase in gabapentin-related drug deaths.    

UK Drugs With Biggest % Increase in Deaths (2011-2022)

DAILY MAIL GRAPHIC

Pregabalin and gabapentin (Neurontin) belong in a class of nerve medication known as gabapentinoids. Their mechanism of action – how they affect the brain and central nervous system – is still unclear two decades after their medical use was approved.

The UK drug statistics are mirrored in a recent analysis of drug tests in the US, which found gabapentin in over 13% of urine samples that tested positive for fentanyl. That’s about twice the number of drug tests in which prescription opioids were found.

Just because a drug is “involved” in an overdose or appears in a drug test doesn’t necessarily mean that drug caused the overdose or is a red flag for addiction. But experts say its long past time for doctors to be more careful about prescribing pregabalin, and to warn patients about potential side effects and the risk of withdrawal.

“How can there be rising deaths from pregabalin and a huge explosion of prescriptions, with all these troubles, and yet doctors are using this drug to treat anxiety?” asks Dr. Mark Horowitz, a clinical research fellow at the UK’s National Health Service.

“Doctors are selling cars without brakes,” Horowitz told The Sunday Times. “It boggles the mind when a drug is showing all these dangers to then use it on a wider variety of people.”

Gabapentinoids Still Overprescribed Despite Warnings

By Pat Anson, PNN Editor

Despite warnings that they are overprescribed for conditions they were never intended to treat, the use of gabapentinoids continues to grow in the United States.

Pregabalin (Lyrica) and gabapentin (Neurontin) are both gabapentinoids, a class of nerve medication initially developed to treat epileptic seizures. Sales of Lyrica and Neurontin tripled a decade ago, when they were touted as safer alternatives to opioids and prescribed off-label for a variety of pain conditions.

In 2018, Michael Johansen, MD, a researcher and family medicine physician, was one of the first to warn that gabapentinoids were being overprescribed, despite little of evidence of their safety and efficacy for pain conditions. Johansen was particularly concerned the drugs were being given to older adults who were long-time users of opioids and benzodiazepines, a class of anti-anxiety medication.

Not much has changed, according to a new research study by Johansen. Using data from a large national survey, Johansen found that 4.7% of U.S. adults were prescribed a gabapentinoid in 2021, up from 4% in 2015 – a statistically significant increase of 17.5% in six years. The growth was primarily driven by gabapentin, as there was little change in pregabalin’s use.

As Johansen found in his earlier study, gabapetinoid use was much more likely in patients who were co-prescribed opioids, muscle relaxants, benzodiazepines or anti-depressants for chronic pain or mental health conditions. The likelihood of a patient being prescribed a gabapentinoid also rises sharply after age 50.

“Gabapentinoids continue to be commonly used in conjunction with other sedating medications, which is concerning in light of the US Food and Drug Administration’s 2019 warning about co-prescribing of gabapentinoids with other central nervous system depressants,” Johansen reported in the Annals of Family Medicine. “Gabapentinoids are likely used for an array of conditions, with the majority being off-label uses for chronic pain with minimal evidence supporting use.”

Despite those warnings, gabapentinoids — gabapentin in particular — are still being promoted as a treatment for all sorts of things, from dental pain to alcoholism to improving your sex life. Gabapentin has been pitched for so many different conditions that a drug company executive infamously called it “snake oil.”

Gabapentin is FDA-approved for epilepsy and neuropathic pain caused by shingles, but is often prescribed off-label for depression, ADHD, migraine, fibromyalgia, bipolar disorder and postoperative pain.  Pregabalin is approved for diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles and spinal cord injuries, but is also prescribed off-label for other types of pain.

Many patients report side-effects from gabapentinoids, such as weight gain, blurred vision, dizziness, sedation and cognitive issues. There are also an increasing number of reports that the drugs are being abused and sold on the street to boost the potency of illicit drugs.

“Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co-use, including respiratory depression and increased risk of opioid overdose death,” Douglas Throckmorton, MD, a top FDA official said when the agency released  its 2019 warning.  

A 2019 study found little evidence that gabapentinoids should be used off-label to treat pain and said their effectiveness was often exaggerated by prescribing guidelines. The CDC’s 2016 opioid guideline recommended gabapentin and pregabalin dozens of times as alternatives to opioids, without saying a word about their abuse or side effects.

The CDC’s 2022 revised opioid guideline takes a more cautious approach, saying gabapentin and pregabalin can have “small to moderate improvements” on pain, but were associated with a moderate risk of adverse events. Evidence on their long-term use was also lacking, according to the CDC.  

Gabapentin Won’t Cure the Opioid Crisis

By Pat Anson, PNN Editor

The risk of prescribing gabapentin (Neurontin) off-label for pain management may finally be sinking into the medical community. The latest sign is an op/ed published in JAMA Internal Medicine, which warns that gabapentin is often ineffective for pain, may raise the risk of overdose, and “will not cure the opioid crisis”    

Gabapentin is a non-opioid medication that was originally developed as an anticonvulsant to treat epileptic seizures. In recent years, gabapentin prescribing has grown 5-fold, with a growing number of physicians prescribing it “off-label” for both acute and chronic pain. Some do it as an alternative to opioids, while others prescribe it in conjunction with opioids.

“Gabapentin is often thought of as a safe alternative for pain management and may be initially enticing as a nonopioid medication, though the evidence for its efficacy in pain control is limited,” wrote lead author Raegan Durant, MD, a Professor at University of Alabama at Birmingham School of Medicine and Associate Editor at JAMA.

“With more restrictive opioid prescribing guidelines, physicians may be struggling to treat pain effectively and more frequently turning to gabapentin as a nonopioid option. However, avoidance of opioids at the expense of either more frequent use of gabapentin or concurrent gabapentin and opioids simply exposes patients to similar risks for harm often without improving the likelihood of actual pain relief.”

The warning from Durant and JAMA Associate Editor Audrey Han, MD, stems from a recent study about the “alarming upward trajectory” of gabapentin being co-prescribed with opioids.  From 2006 to 2018, overlapping prescriptions for the two medications rose by 344 percent, with many of the prescriptions being written by pain specialists.

Gabapentin is only approved by the Food and Drug Administration to treat partial seizures, nerve pain from shingles and restless leg syndrome, but is also widely prescribed off-label for fibromyalgia, neuropathy, migraine and other pain conditions – despite little evidence supporting its use.  

In addition to poor pain relief, many patients who take gabapentin report side effects such as dizziness, confusion, drowsiness, mood swings and weight gain. A 2019 study linked gabapentin to a growing number of attempted suicides.

Gabapentin may cause euphoria, feelings of intoxication, and enhance the effects of opioids and other drugs. The FDA has warned that gabapentin may cause serious breathing problems and respiratory depression, especially in older adults. A recent study found gabapentin raises the risk of delirium in seniors recovering from surgery.

Gabapentin and Pregabalin Only ‘Modestly Effective’ for Pain

By Pat Anson, PNN Editor

A new review of clinical studies on the use of gabapentin (Neurontin) and pregabalin (Lyrica) in pain management found the drugs are only “modestly effective” and could be risky for some pain patients.

Gabapentin and pregabalin belong to a class of nerve medication called gabapentinoids, which were originally developed as anticonvulsants to treat epileptic seizures. In recent years, however, they have been increasingly prescribed off-label as an alternative to opioids in managing pain. About one in five U.S. adults with chronic pain are prescribed a gabapentinoid.  

"Treating pain has been problematic for a long time, and we're still dealing with the fallout from opioid overuse," says lead author Craig Williams, PharmD, a clinical professor at Oregon State University College of Pharmacy. "Gabapentinoids are modestly effective for certain patients; they are rarely extremely effective, and they are not effective at all for some patients because the mechanisms of the pain don't match up with the mechanisms of the drug.

"Doctors who prescribe gabapentinoids for pain should do so with their eyes wide open and be prepared to stop them if they are ineffective or cause too many side effects."

The study findings, published in the journal Drugs, found that many of the clinical trials for gabapentin and pregabalin were of short duration, had a small number of participants, and performed only slightly better than placebos in reducing pain. Many patients who take the medications also report side effects such as dizziness, confusion, drowsiness, mood swings and weight gain.

"Treating pain is about making patients more functional so they can live their lives better, and if they have to deal with adverse effects for a little pain relief, their lives may not be improving," said Williams.

Pregabalin has been approved by the Food and Drug Administration for four pain conditions: post-herpetic neuralgia (shingles), diabetic peripheral neuropathy, spinal cord injury, and fibromyalgia. Gabapentin has only been approved by the FDA for post-herpetic neuralgia.

Despite the limits on their uses, many doctors legally prescribe the drugs “off-label” for pain conditions such as migraines, back pain, post-operative pain and even dental pain. Gabapentin was once derisively referred to as “snake oil” by a pharmaceutical executive because it is so widely prescribed for so many different pain conditions, despite weak evidence.

"In addition, we found that the trials used by the FDA to approve gabepentinoids for pain indications had a couple of key structural weaknesses," Williams said. "The trials tended to be short, typically lasting one to three months, and the trials typically excluded the simultaneous use of other medications that affect the central nervous system. That's important because patients taking gabepentinoids are rarely taking them exclusively; they're often prescribed in conjunction with opioids, muscle relaxants or other epilepsy drugs."

Gabapentin can cause euphoria and feelings of intoxication, and make the effect of opioids and other drugs seem stronger. A 2019 study linked gabapentin to a growing number of attempted suicides.

That same year, the FDA warned that gabapentin and pregabalin may cause serious breathing problems and respiratory depression, especially in older adults. A recent study found that gabapentin raises the risk of delirium in older adults recovering from surgery.

Gabapentin Raises Risk of Delirium in Older Surgery Patients

By Pat Anson, PNN Editor

It’s become trendy in recent years for U.S. hospitals to use gabapentin (Neurontin) as a “safer” alternative to opioids for post-operative pain.  But a large new study has found that gabapentin increases the risk of delirium and other adverse health effects in older patients recovering from surgery.

The study, published in JAMA Internal Medicine, looked at nearly a million patients over the age of 65 who had major surgical procedures, including cardiac, orthopedic and gastrointestinal surgeries. About 12% of the patients received gabapentin and other analgesics for perioperative pain management between the day of surgery and two days after surgery.

Researchers found that gabapentin “modestly increased” the risk of delirium, a mental state in which a person becomes confused, disoriented and unable to think or remember clearly. Patients who received gabapentin were also more likely to be prescribed antidepressants and other anti-psychotic drugs, and to develop pneumonia.

“Considering the increasing number of major surgeries performed in older adults, and the negative consequences of perioperative delirium, our findings raise concern about an increasingly adopted clinical practice that involves routine use of gabapentin as part of multimodal analgesia,” wrote lead author Dae Hyun Kim, MD, a geriatrician and epidemiologist at Brigham and Women's Hospital and Assistant Professor of Medicine at Harvard Medical School.

“On the basis of these findings and those of meta-analyses of RCTs (randomized controlled trials) showing a weak opioid-sparing effect of gabapentin, clinicians should reconsider routine use of gabapentin for perioperative pain management among older adults and individualize the treatment decision after assessing the risk of immediate harms vs opioid-sparing benefits of perioperative gabapentin use.”

‘Windfall Medication’

Although gabapentin is an anti-convulsant that was originally developed to treat epilepsy, it is increasingly prescribed “off-label” to treat various types of pain. In 2016, the American Pain Society recommended that gabapentin be used “around the clock” for post-operative pain because it lowered pain scores and reduced the use of opioids. But studies later found the drug was ineffective for post-operative pain and actually increased the risk of an overdose.

An editorial published in JAMA Internal Medicine said the new study demonstrates that the risks of gabapentin outweigh its potential benefits in older patients.

“These results are consistent with what is now a growing body of literature suggesting that gabapentin may not be the windfall medication for perioperative pain management that surgeons hoped it might be for decreasing opioid use. The adverse events reported in this study (delirium, antipsychotic use, and pneumonia) add to similar findings that gabapentin, especially when used concomitantly with opioids, increases the risk of postoperative sedation and dizziness,” wrote lead author Zachary Marcum, PharmD, University of Washington School of Pharmacy.  

“As the use of gabapentin continues to rise, it is critically important clinicians understand its risks, especially for older adults. Poorly controlled postoperative pain is associated with several complications, including cognitive impairment, delirium, depression, decreased mobility, and longer recovery.”

It’s a common misconception that patients often become addicted to opioids after surgery. A 2016 Canadian study found that long term opioid use after surgery is rare, with only 0.4% of older adults still taking opioids a year after major elective surgery. A 2018 study at Harvard Medical School had similar findings. Only 0.6% of patients who were prescribed opioids for post-operative pain were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Should Gabapentin Be Used for Dental Pain?

By Pat Anson, PNN Editor

Since it was first approved as an anti-seizure medication in the 1990’s, gabapentin (Neurontin) has become one of the most widely studied and prescribed drugs in world.  Although gabapentin is only approved by the FDA for epilepsy and postherpetic neuralgia (shingles), it is widely prescribed off-label for fibromyalgia, neuropathy and many other types of pain.

Hundreds of clinical trials have been conducted to find new uses for gabapentin -- for everything from asthma and obesity to alcoholism and improving your sex life. Gabapentin has been pitched for so many different conditions that a drug company executive infamously called it “snake oil.”

Now gabapentin is being touted as a “promising alternative” to opioids for dental pain. In a new study at the University of Rochester Medical Center’s Eastman Institute for Oral Health (EIOH), researchers found that gabapentin, when combined with ibuprofen or acetaminophen, was more effective than opioids in relieving pain after tooth extractions.  

“We hypothesized that using a combination of the non-opioid pain medications and adding gabapentin to the mix for pain would be an effective strategy to minimize or eliminate opioids for dental pain,” said Yanfang Ren, DDS, a dentistry professor at EIOH.   

Ren and his colleagues treated over 7,000 patients at an urgent dental care clinic with different combinations of opioids, ibuprofen, acetaminophen and gabapentin after tooth extractions. The “failure rates” of the medications were determined by how often patients returned to the clinic for additional pain relief.

The study findings, published in JAMA Network Open, found that non-opioid medications, including those with gabapentin, had failure rates significantly lower than opioids.      

Dental Pain Failure Rates

• 0.9% Acetaminophen/ibuprofen

• 3.4% Gabapentin/acetaminophen

• 5.3% Gabapentin/ibuprofen

• 9.2% Codeine/acetaminophen

• 19.4% Hydrocodone/acetaminophen

• 31.3% Other opioid combinations

Providers at the dental clinic have already put their findings into practice by sharply reducing the use of opioids. Prior to that, about 1,800 patients at the clinic were treated each year with opioids. Researchers estimate the reduced opioid prescribing may have prevented 105 of those patients from developing a problem with “persistent opioid use.”

“This study represents continued efforts by our team and other dentists to minimize the use of opioids for dental pain,” said Eli Eliav, DMD, the director of EIOH. “Additional studies, preferably randomized controlled clinical trials, are needed to confirm the safety and effectiveness of this approach. It is our duty to continuously seek safe and effective treatment for our patients in pain.”

Gabapentin has issues of its own. Patients prescribed gabapentin often complain of mood swings, depression, dizziness, fatigue and drowsiness, and a 2019 review found little evidence gabapentin should be used off-label to treat pain. There are also many reports that gabapentin is being abused and sold on the streets because it can heighten the effects of other drugs.

Gabapentin Is Not a Good Substitute for Rx Opioids

By Crystal Lindell, PNN Columnist 

Gabapentin (Neurontin) is not a good medication for pain relief. If it was, everyone in pain would just take it. 

A lot of doctors seem to think it is a direct substitute for opioids though. And it’s leading to a lot of suffering. 

A doctor first gave me gabapentin back in 2012. That’s when I started having debilitating pain around my right ribs. I didn’t know it yet, but it was the kind of pain that would never go away.

At the time, I was extremely uninformed on how I’d be treated as a patient with no known cause for my pain. I assumed that because I could point to exactly where the pain was coming from that the doctors would be able to figure out the cause and then fix it. That’s what always happened on House, ER, Scrubs, Grey’s Anatomy, and General Hospital.

When that didn’t happen, I still assumed my doctor would believe me. That, while I sat there crying in his office, confessing my plan to kill myself to escape the pain, at the very least he would give me the most effective medication he knew of for treating the pain. 

I was wrong on all accounts.  

While my doctor pretended he was giving me the most effective medication he knew of, he instead handed me a prescription for gabapentin. 

And I took it. Exactly as prescribed. 

He never went over side effects with me, and the list on the pharmacy pamphlet was so long that I assumed most of them were rare. So when I started gaining weight, I blamed it on being home and in pain all the time.  

When gabapentin didn’t help with the pain, I went back to my doctor and told him as much. He increased the dose, while assuring me that that was all that was needed. 

Wash, rinse, repeat, until I was on the highest allowable dose. Still with no relief. 

And to be clear, the pain was awful. It was worse than whatever you just thought of. And it was constant. That’s the killer. It never let up. I never got a break. I’d go days without even minutes of sleep because the pain kept me awake. 

The pain was so bad that suicide became a logical treatment option. What’s the point in living a life with no quality in it?

I started showing up at my doctor’s office when they opened, in tears after being awake all night in excruciating pain, asking for help. Still giving my doctor 100 percent of my trust. Still assuming he had my best interest in mind.  

I remember sitting on the exam table, wanting to die, while my friend who had driven me to his office at 7 a.m. held my hand. I begged my doctor for help. And he said, “Well what do you want me to do? I can’t up your gabapentin prescription any more. You’re on the max dose.” And then he sent me home. 

I didn’t even know enough about pain management at that point to want opioids, much less to know they were being denied to me. I didn’t know the doctors were prescribing a seizure medication because of opioid phobia. 

Not long after that, my doctor would break up with me. Or, well, whatever you call it when a doctor says he will no longer treat you and then follows it up with, “So don’t come in anymore.”

He literally gave up. And I would have too, if my pain had gone on much longer. 

‘Opioids Saved My Life’

Eventually, I found a new doctor at a university hospital. He believed me. He prescribed me enough opioids to function. And that’s literally the reason I’m still here. 

Opioids saved my life. In many ways, gabapentin almost took it. 

But it also did something else. It destroyed my trust in doctors and medical professionals. If they could look me in the eye while handing me a prescription they knew wouldn’t help me, what else could they lie about? What else were they hiding from me?

Back then, prescribing gabapentin in place of opioids was a relatively new practice. After that experience, I had hoped it would go away. Instead, it gained traction. 

According to data from IQVIA, gabapentin was prescribed over 33 million times in the U.S. in 2011, which is about the time opioid prescriptions peaked. By 2018, the number of prescriptions for gabapentin had increased to over 67 million. 

Anecdotally, a lot of people I know with various pain ailments have been offered gabapentin in place of opioids by their doctors as recently as this year.

Since I’m so open when discussing my health issues, it’s common for people I know to ask what my experience was like on various medications. I never know what to tell them when they ask about gabapentin. I’m too worried about being wrong to warn them off of it completely. After all, what if it helps them? I don’t want to keep them from anything that might relieve their pain.

Doctors don’t seem to grapple with this though. For them, addressing patient pain has moved over into optional, right alongside unnecessary cosmetic surgery.

They are literally doing harm. And the practice of giving unproven medication out for pain continues.

Here’s a 2019 article by The New York Times detailing this problem, and the lack of evidence supporting the use of gabapentin for pain.

“One of the most widely prescribed prescription drugs, gabapentin, is being taken by millions of patients despite little or no evidence that it can relieve their pain,” wrote columnist Jane Brody.

In other words, it’s been two years since The New York Times made this clear, but doctors are still prescribing it for pain.

That article misses one key point though. Brody says there are non-gabapentin alternatives to opioids that help pain, but then goes on to list “physical therapy, cognitive behavioral therapy, hypnosis and mindfulness training.”

As a pain patient, I’m here to tell you that none of those are real alternatives to opioids either. While they can all be helpful tools, they can’t replace opioids for real pain relief.

Which brings us to the problem. Our society, with guidance from the CDC, decided to take away everyone’s opioids – without having a real plan to replace them. Because there are no alternatives as good as opioid pain medication.

The general public might worry about their pain treatment if the CDC admitted that. So instead, we are sold a lie about gabapentin. We are told it is just as effective as hydrocodone for all sorts of pain, and that anyone who insists on opioids is just looking to get high.

No matter how much people use gabapentin, physical therapy and mindfulness to treat pain, they just don’t work the way opioids do.

Opioid-phobia is a big messy topic, and doctors replacing opioids with gabapentin are just one small part of that story. But for people who are suffering because of their doctor’s overreliance on gabapentin, it often feels like the most important part. 

There’s such an easy answer to this problem too: Just give people opioid medication. When used responsibly, it’s incredibly safe, cheap, and best of all, it actually works.

Crystal Lindell is a journalist who lives in Illinois.  After five years of unexplained rib pain, Crystal was finally diagnosed with hypermobile Ehlers-Danlos syndrome.

Over-the-Counter Pain Meds and Gabapentin Recommended for Trauma Patients

By Pat Anson, PNN Editor

Over-the-counter pain medications and gabapentin are the best line of treatment for trauma patients suffering from acute short-term pain, according to new study at a Texas hospital that minimizes the use of opioids.

Researchers at the Red Duke Trauma Institute at Memorial Hermann-Texas Medical Center in Houston assessed two different combinations of non-opioid pain relievers in over 1,500 patients being treated for acute trauma, such as bone fractures and head injuries.

The treatment protocol that was deemed superior included a combination of inexpensive over-the-counter drugs such as acetaminophen and naproxen, with the nerve medication gabapentin (Neurontin). Opioids such as tramadol and oxycodone were only prescribed for breakthrough pain.

"Narcotics are not the mainstay of therapy for acute pain," said lead author John Harvin, MD, a trauma surgeon at the hospital and an associate professor at The University of Texas Health Science Center at Houston. "The research shows us that seriously injured people with acute pain can effectively be treated with an opioid-minimizing strategy."

The study findings, published in the Journal of American College of Surgeons, showed that a first-line pain regimen that used acetaminophen, ketorolac, naproxen, gabapentin or lidocaine patches reduced the use of opioids without a significant difference in pain scores. Only 62 percent of the patients were discharged with an opioid prescription.

"We used a generic pain regimen that is affordable at discharge. The discharge medications acetaminophen and naproxen can be bought over the counter. The only drug that requires a prescription is gabapentin and an as-needed opioid, if prescribed," Harvin explained.

The use of gabapentin as a treatment for acute pain is controversial, because recent studies show it has no significant analgesic effect and is increasingly being abused. In 2019, the Food and Drug Administration warned that serious breathing problems can occur in patients who take gabapentin with opioids or other drugs that depress the central nervous system.

But the use of gabapentin and over-the-counter pain relievers is now the standard treatment protocol for trauma patients at Memorial Hermann-Texas Medical Center, and physicians there are working to adapt it for the treatment of acute burn pain.

"The best way to decrease someone's risk for long-term (opioid) use is to minimize their exposure during hospitalization and at discharge, and we now know there are excellent non-opioid medications available that effectively treat pain,” said Harvin. “We know that culture change will take time and effort, but we're excited to be learning how to best leverage opioid-minimizing drugs to improve care, and to offer a new model that can be adopted by any trauma center."

The risk of long-term opioid use after an emergency room visit is actually quite low. A 2017 study by the Mayo Clinic found that only about one percent of emergency room patients given an opioid prescription progressed to long term use.

"Our paper lays to rest the notion that emergency physicians are handing out opioids like candy," said lead author Molly Moore Jeffery, PhD, a Mayo Clinic researcher. “Most opioid prescriptions written in the emergency department are for shorter duration, written for lower daily doses and less likely to be for long-acting formulations."

Gabapentinoids Riskier for Surgery Patients

By Pat Anson, PNN Editor

Another study is casting doubt on the use of gabapentinoids such as Lyrica (pregabalin) and Neurontin (gabapentin) for pain relief during and after surgery.

Gabapentioids are a class of nerve medication originally developed to treat convulsions, but the drugs are increasingly being used as a trendy alternative to opioids for acute and chronic pain. Some U.S. hospitals are even using gabapentinoids for surgical pain and have phased out or reduced the use of opioids.

In an analysis of over 5 million adults admitted for major surgery in the U.S. from 2007 to 2017, researchers at Harvard Medical School found that using gabapentinoids with opioids increases the risk of overdose, respiratory depression and other adverse events. Researchers say the additional risk was “extremely low” and would result in one additional overdose for every 16,000 patients.

“Our findings add to the growing evidence that gabapentinoids can potentiate the respiratory depressant effects of opioids,” researchers reported in JAMA Network Open. “The events were rare… (but) patients receiving multimodal pain management therapy that includes gabapentinoids should be closely monitored for possible respiratory depression.”

The study did not examine whether gabapentiniods were effective in treating surgical pain or if they improved the analgesic effect of opioids.

In an editorial also published in JAMA Network Open, a pain management expert said more studies were needed to see if gabapentiniods were worth the additional risk.

“The evidence in support of the analgesic benefit of gabapentinoids combined with opioids for postoperative analgesia is equivocal; there is no real support that adding gabapentinoids to opioid pain relievers offers additive, much less synergistic, enhancements to pain control,” wrote Joseph Pergolizzi, Jr, MD, Chief Operating Officer of NEMA Research.  

“Considering that combination analgesic regimens generally reduce overall opioid consumption, this study is important because it shows that this may not necessarily translate to reducing opioid-associated adverse events. As combination analgesia gains traction for in-hospital acute painful conditions, such as postsurgical pain, it is important to be guided by evidence rather than intuition.”

No Significant Analgesic Effect

A recent study by Canadian researchers also found little evidence to support the use of gabapentinoids for surgical pain.

“No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events,” wrote lead author Michael Verret, MD, a resident at Laval University in Quebec City.  

These and other findings contradict guidelines published by the American Pain Society in 2016, which advocate “around the clock” use of gabapentin, pregabalin and other non-opioid drugs both before and after surgery.

The risk of becoming addicted or dependent on opioids after surgery is actually quite low. A 2016 study found that only 0.4% of elderly patients who were prescribed opioids for post-operative pain were still using them a year after their surgeries. Another study by Harvard researchers found that only 0.2% of surgery patients prescribed opioids were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Gabapentinoids Involved in a Third of Overdoses in Scotland

By Pat Anson, PNN Editor

A new study in Scotland is shining more light on the risks of overprescribing gabapentin (Neurontin) and pregabalin (Lyrica). The two drugs belong to a class of nerve medication called gabapentinoids, which are increasingly prescribed in Western nations to treat chronic pain.

In 2018, there were 1,187 accidental drug-related deaths (DRDs) in Scotland – the highest overdose rate in the European Union — and gabapentinoids were involved in about a third of them.

According to research published in the British Journal of Anaesthesia, gabapentin was implicated in 15.2% of fatal overdoses in Scotland, while pregabalin was linked to 16.5% of drug deaths. That’s up from 3% and 1% of fatal overdoses, respectively, in 2012.

Researchers say deaths involving gabapentinoids are rising because they are frequently co-prescribed with opioids and other medications that depress the central nervous system and raise the risk of overdose. Drug diversion also plays a role.

“Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death. Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication,” wrote lead author Nicola Torrance, PhD, Senior Research Fellow at the School of Nursing & Midwifery, Robert Gordon University, in Aberdeen, Scotland.

From 2006 to 2016, the number of pregabalin prescriptions in Scotland rose by an astounding 1,600 percent, while prescriptions for gabapentin quadrupled. About 60% of the time, gabapentin was co-prescribed with an opioid, benzodiazepines or both.  

Gabapentinoids are also showing up in Scotland’s illicit drug supply. Drug users have found they can heighten the effects of heroin, marijuana, cocaine and other substances. In the Scottish region of Tayside, gabapentinoids were involved in 39% of drug deaths. About three out of four of those overdose victims did not have a prescription for the drug.

In addition to overdoses, gabapentinoids have also been associated with increased risk of suicidal behavior, accidental injuries, traffic accidents and violent crime. UK health officials were so alarmed by misuse of the drugs and the rising number of deaths that gabapentin and pregabalin were reclassified as controlled substances in 2019.

Gabapentin is not currently scheduled as a federally controlled substance in the United States, but pregabalin is classified as a Schedule V controlled substance, meaning it has low potential for addiction and abuse.  

A 2019 clinical review found little evidence that gabapentinoids should be used off-label to treat pain and that prescribing guidelines often exaggerate their effectiveness. The U.S. Food and Drug Administration also recently warned that serious breathing problems can occur in patients who take gabapentin or pregabalin with opioids or other drugs that depress the central nervous system.

Gabapentinoids Ineffective for Pain Relief After Surgery

By Pat Anson, PNN Editor

Would you want to take Lyrica (pregabalin) or Neurontin (gabapentin) for pain relief after a major surgery? Both drugs belong to a class of nerve medication called gabapentinoids that are increasingly being prescribed to patients perioperatively (after surgery) as an alternative to opioid medication.

But gabapentinoids also have risks and there is little evidence to support their use for postoperative pain relief, according to a large new study by a team of Canadian researchers.  

“No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients,” wrote lead author Michael Verret, MD, a resident at Laval University in Quebec City.  

Verret and his colleagues conducted a meta-analysis of 281 clinical trials involving nearly 25,000 patients undergoing a wide range of surgeries, including orthopedic, spinal and abdominal operations.

Their findings, recently published in the journal Anesthesiology, indicate that the analgesic benefits of pregabalin and gabapentin after surgery are negligible, regardless of the dose or type of operation. Gabapentinoids were also ineffective in preventing chronic pain from developing after surgery, one of the primary justifications for using the drugs postoperatively.

“Gabapentinoids were also associated with a greater incidence of adverse events, namely dizziness and visual disturbance, while other major adverse events such as respiratory depression and addiction are not reported or are underreported,” said Verret.

The findings contradict guidelines published by the American Pain Society (APS) in 2016,  which advocate “around the clock” use of gabapentin, pregabalin and other nonopioid drugs both before and after surgery.

“The panel recommends use of gabapentin or pregabalin as part of a multimodal regimen in patients who undergo surgery. Both medications are associated with reduced opioid requirements after major or minor surgical procedures, and some studies reported lower postoperative pain scores,” the APS guideline states.

“The panel suggests that clinicians consider a preoperative dose of gabapentin or pregabalin, particularly in patients who undergo major surgery or other surgeries associated with substantial pain, or as part of multimodal therapy for highly opioid-tolerant patients.”

‘Evidence of Harm’

Although opioid addiction is relatively rare after surgery, dozens of U.S. hospitals followed the lead of the APS and other medical guidelines by stopping the use of opioids for certain surgeries.

Cleveland Clinic Akron General Hospital, for example, adopted a policy of only using gabapentin and other non-opioid analgesics for colorectal operations.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased.”

— Dr. Evan Kharasch

Critics say gabapentinoids have become a trendy alternative for post-surgical pain relief, even though evidence supporting their use is minimal.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased. If any potential benefits exist in ‘special populations,’ published reports have yet to identify the benefits or the populations,” lead author Evan Kharasch, MD, Editor-in-Chief of Anesthesiology, wrote in an editorial.

“The good intentions that led to routine gabapentinoid use should be redirected to lead the way out. The French Society of Anesthesia and Intensive Care Medicine now states that gabapentinoids should not be used systematically or in outpatient surgery. Other societies should follow. As the weight of evidence has shifted and the risk–benefit balance tilted away from benefit, evidence-based practice impels revising if not eliminating the routine use of perioperative gabapentinoids in adults.”

It's too late for the APS to change its guideline. The organization filed for bankruptcy in 2019, ironically because of the high cost of legal fees in defending itself against opioid litigation.

While the CDC’s controversial opioid guideline does not advocate using gabapentinoids for post-surgical pain, it does recommend their use in treating chronic pain -- with little to no mention of their side effects.

One of the co-authors of the CDC guideline, Dr. Roger Chou, also played a significant role in drafting the APS guideline. Chou is currently heading much of the research being conducted by the CDC as it prepares to update and possibly expand its 2016 guideline.

Study Finds Limited Evidence to Support Use of Non-Opioid Drugs for Chronic Pain

By Pat Anson, PNN Editor

A new study by federal researchers has found limited evidence to support the use of non-opioid medications in treating chronic pain conditions such as fibromyalgia, neuropathy, rheumatoid arthritis and low back pain.

Only small improvements in pain and function were found in the use of anti-convulsants and non-steroidal anti-inflammatory drugs (NSAIDs), while moderate improvement was found in the use of some antidepressants.

Researchers noted that evidence was “too limited to draw conclusions” on long-term use of non-opioid drugs, and “no treatment achieved a large improvement in pain or function.” They also cautioned that “careful consideration of patient characteristics is needed in selecting nonopioid drug treatments” because of the risk of side effects.

The report was prepared for the Agency for Healthcare Research and Quality (AHRQ) by the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University. The EPC has recently finalized two other studies on the use of opioids and nonpharmacological treatments for chronic pain.

Unlike their report on opioids, EPC researchers did not consult with technical experts and peer reviewers associated with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

The researchers analyzed nearly 200 clinical studies and systematic reviews of non-opioid medication. Only 25 of the studies were rated as good quality and only 8 lasted a year or more. The pharamceutical industry funded 82 percent of them.

The EPC report is more cautious than other federal studies on the use of non-opioids such as pregabalin (Lyrica) and gabapentin (Neurontin).  Side effects from those drugs were often so severe that some patients stopped taking them and dropped out of clinical studies.

“Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness),” EPC researchers found. “Dose reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.”

The EPC study is in marked contrast to the 2016 CDC opioid guideline, which recommends pregabalin, gabapentin and NSAIDs as alternatives to opioids with little to no mention of their side effects.

Other researchers have also warned that the effectiveness of gabapentin and pregabalin, which belong to a class of anti-convulsant drugs known as gabapentinoids, is often exaggerated in prescribing guidelines.

“Gabapentinoids have become frequent first-line alternatives in patients with chronic pain from whom opioids are being withheld or withdrawn, as well as in patients with acute pain who traditionally received short courses of low-dose opioid,” researchers at the University of South Carolina School of Medicine warned in a 2019 study.

“The evidence to support off-label gabapentinoid use for most painful clinical conditions is limited. For some conditions, no well-performed controlled trials exist.”

The EPC’s trio of studies on opioids, non-opioid drugs and non-pharmacological treatments are expected to help guide the CDC as it prepares an update and expansion of its 2016 opioid guideline, which is expected in late 2021. The update is likely to include new guidelines for treating short term, acute pain.  

How will CDC interpret the EPC findings on opioids and non-opioids? One outcome is suggested in the opioid study.

“Findings support the recommendation in the 2016 CDC guideline that opioids are not first-line therapy and to preferentially use nonopioid alternatives,” researchers said.

Should Gabapentin Be Used to Treat Alcohol Abuse?

By Pat Anson, PNN Editor

Gabapentin (Neurontin) is so widely prescribed for so many different conditions that a Pfizer executive infamously compared it to “snake oil” in a 1999 email.

“Gabapentin is the snake oil of the twentieth century. It has been successful in just about everything they have studied,” said Christopher Wohlberg, who was a Pfizer Medical Director at the time.

Although only approved by the FDA to treat epilepsy and neuropathic pain caused by shingles, gabapentin is widely prescribed off-label to treat fibromyalgia, anxiety, depression, ADHD, migraine, bipolar disorder, restless leg syndrome and a growing number of other conditions.  

Already the 6th most widely prescribed drug in the United States, gabapentin is also being touted as a treatment for alcohol abuse.

In a small study published in JAMA Internal Medicine, researchers found that gabapentin was effective in treating patients with alcohol use disorder (AUD) – problem drinking that has become severe. Compared to a placebo, gabapentin significantly increased abstinence and reduced heavy drinking days, especially for those who suffer from symptoms of alcohol withdrawal.

“The weight of the evidence now suggests that gabapentin might be most efficacious after the initiation of abstinence to sustain it and that it might work best in those with a history of more severe alcohol withdrawal symptoms,” concluded lead author Raymond Anton, MD, an addiction psychiatrist and professor at the Medical University of South Carolina.

“Armed with this knowledge, clinicians may have another alternative when choosing a medication to treat AUD and thereby encourage more patient participation in treatment with enhanced expectation of success.”

As many as 30 million Americans have AUD, but only about a million are taking a medication to help them reduce drinking or maintain abstinence. The FDA has approved three drugs (naltrexone, disulfiram and acamprosate) for the treatment of alcohol abuse.

Side Effects and Abuse

The suggestion that gabapentin should also be prescribed for AUD comes at a time when the drug is already under scrutiny for its abuse and side effects, including an association with a growing number of suicide attempts. Patients prescribed gabapentin often complain of mood swings, depression, dizziness, fatigue and drowsiness.    

Although the CDC’s controversial 2016 opioid guideline calls gabapentin and its chemical cousin pregabalin “first-line drugs” for neuropathic pain, a recent clinical review found little evidence that either drug should be used off-label to treat pain.

Gabapentin does not carry the same risk of addiction and overdose as opioid pain relievers, but illicit drug users have discovered that gabapentin can heighten euphoria caused by heroin and other illicit opioids. Should a drug like that be used to treat addiction?

Hundreds of clinical studies are underway to find new uses for gabapentin, not only for alcohol abuse, but for a cornucopia of conditions such as obesity, insomnia, breast cancer, asthma, menopause and overactive bladder. One recent study even found that gabapentin improves sexual desire in women with vulvodynia.

Instead of finding new uses for an old medication, maybe it’s time to come up with a new drug.

FDA Warns of Serious Breathing Problems Caused by Gabapentinoids

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is warning that serious breathing problems can occur in patients who use gabapentin or pregabalin with opioids or other drugs that depress the central nervous system. The elderly and patients with lung problems are at higher risk when they use the drugs, according to an FDA drug safety communication.

The advisory is the latest in a series of warnings about gabapentinoids, a class of nerve medication increasingly prescribed as an alternative to opioid painkillers. There are growing reports of gabapentinoids being abused or raising the risk of overdose and suicide.

“Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co-use, including respiratory depression and increased risk of opioid overdose death,” Douglas Throckmorton, MD, deputy director for Regulatory Programs in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In response to these concerns, we are requiring updates to labeling of gabapentinoids to include new warnings of potential respiratory depressant effects. We are also requiring the drug manufacturers to conduct clinical trials to further evaluate the abuse potential of gabapentinoids, particularly in combination with opioids, with special attention being given to assessing the respiratory depressant effects.”

Gabapentinoid products include gabapentin, which is marketed under the brand name Neurontin, and pregabalin, which is marketed as Lyrica. Generic versions of the drugs are also available.

Gabapentinoids were originally developed to prevent seizures, but their use has tripled over the past 15 years. The drugs are approved to treat a variety of chronic pain conditions, such as fibromyalgia, neuropathy and shingles. They are also widely prescribed off-label.

According to the FDA, over 13 million people filled a prescription for gabapentin in 2016, while over 2 million patients were prescribed pregabalin. Nearly one in five of those patients were also taking opioids.

“Pairing an opioid with any CNS depressant – a gabapentinoid, benzodiazepine, sedating antidepressant, sedating antipsychotic, antihistamine, or other product – will increase the risk of respiratory depression. Shifting treatment from one CNS depressant to another may pose similar risks,” the FDA said.

A Dozen Deaths

The agency said it received 49 case reports of serious breathing problems in patients taking gabapentinoids, including 12 people who died from respiratory depression. It’s advising doctors, caregivers and patients taking gabapentinoids to be alert for signs of confusion, disorientation, dizziness, sleepiness, slow or shallow breathing, unresponsiveness, or bluish-colored lips, fingers and toes.

A 2018 study by Australian researchers found that gabapentinoids often had side effects such as drowsiness, dizziness and nausea. Another study found that combining gabapentin with opioids significantly raises the risk of dying from an overdose. And a recent analysis of calls to U.S. poison control centers found a significant increase in suicide attempts involving gabapentin.

There have also been increasing reports of gabapentin and pregabalin being abused by illicit drug users, who have learned they can use the medications to heighten the high from heroin, marijuana, cocaine and other substances.

A recent study published in JAMA Internal Medicine found little evidence that gabapentinoids should be used off-label to treat pain and said their effectiveness was often exaggerated by prescribing guidelines. The CDC’s 2016 opioid guideline recommends gabapentin and pregabalin dozens of times as alternatives to opioids, without saying a word about their abuse or side effects.

“Our goal in issuing today’s new safety labeling change requirements is to ensure health care professionals and the public understand the risks associated with gabapentinoids when taken with central nervous system depressants like opioids or by patients with underlying respiratory impairment. However, we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications,” Throckmorton said.