Gabapentinoids Raise Risk of Suicide and Overdose in Younger People

By Pat Anson, PNN Editor

Gabapentinoids – a class of nerve medication widely prescribed to treat chronic pain – increase the risk of suicide, overdose, traffic accidents and head or body injuries in younger people, according to a large new study published in The British Medical Journal.

Sales of the two main gabapentinoids, pregabalin (Lyrica) and gabapentin (Neurontin), have tripled in recent years in the United States, where they are often promoted in prescribing guidelines as safer alternatives to opioids.

A team of researchers followed nearly 192,000 people enrolled in the Swedish Prescribed Drug Register who filled prescriptions for gabapentinoids on at least two consecutive occasions from 2006 to 2013. That information was compared to data in the Swedish Patient Register, which collects information on hospital admissions and outpatient care, as well as the Swedish Cause of Death Register.

Over the study period, researchers found that patients taking gabapentinoids had higher rates of suicide or suicidal behavior (5.2%), unintentional overdose (8.9%), traffic accidents (6.3%) and head or body injuries (36.7%) than the general population.

The risks were strongest for people who were prescribed pregabalin and were most pronounced among adolescents and young adults aged 15 to 24.  Patients aged 55 and older taking gabapentinoids were not at greater risk.

Researchers believe the drugs may have more impact on younger people because they have faster metabolisms, which could lead to withdrawal problems that affect their impulsivity and emotions.

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“Overall, gabapentinoids seem to be safe for a range of outcomes in older people. However, the increased risks found in adolescents and young adults prescribed gabapentinoids, particularly for suicidal behaviour and unintentional overdoses, warrant further research,” said lead author Seena Fazel, MD, of the University of Oxford in England.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people, and those with substance use disorders. Further restrictions for off-label prescription may need consideration.”

Pregabalin is approved by the FDA to treat diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles and spinal cord injuries; while gabapentin is approved for epilepsy and post-herpetic neuralgia. Both drugs are also widely prescribed off-label to treat back pain, depression, migraine and other chronic conditions.

Gabapentinoids are increasingly being used recreationally by addicts who have found the medications enhance the effects of heroin and other opioids. The drugs were recently classified as controlled substances in the UK.

Gabapentin is not currently scheduled as a controlled substance by the DEA, while Lyrica is classified as a Schedule V controlled substance, meaning it has low potential for addiction and abuse.  

A recent clinical review found little evidence the drugs should be used off-label to treat pain and that prescribing guidelines often exaggerate their effectiveness. The CDC’s controversial opioid guideline, for example, calls gabapentin and pregabalin “first-line drugs” for neuropathic pain.

“Despite documentation that these drugs were promoted improperly for off-label treatment of pain, the recent rapid increase in prescribing of gabapentinoids suggests a persisting sense among clinicians that gabapentinoids are highly effective pain medications,” wrote Christopher Goodman, MD, and Allan Brett, MD, of the University of South Carolina School of Medicine.

“Guidelines and review articles have contributed to this perception by often uncritical extrapolation from FDA-approved indications to off-label use.”

Doctors Say Guidelines Exaggerate Effectiveness of Lyrica and Neurontin

By Pat Anson, PNN Editor

There is little evidence that gabapentin (Neurontin) and pregabalin (Lyrica) should be used off-label to treat pain and prescribing guidelines often exaggerate their effectiveness, according to a new clinical review in JAMA Internal Medicine.

Gabapentin and pregabalin belong to a class of nerve medication known as gabapentinoids. The drugs were originally developed to prevent seizures, but their use has tripled over the past 15 years as more doctors prescribed them for a variety of chronic pain conditions. It is a common practice for doctors to prescribe drugs “off label” for treatments that are not FDA-approved.

“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,” wrote Christopher Goodman, MD, and Allan Brett, MD, of the University of South Carolina School of Medicine.

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

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

The drugs are sold by Pfizer under the brand names Lyrica and Neurontin. The company has paid nearly $1 billion in fines for misleading and improper marketing of the drugs for off-label use.

“Despite documentation that these drugs were promoted improperly for off-label treatment of pain, the recent rapid increase in prescribing of gabapentinoids suggests a persisting sense among clinicians that gabapentinoids are highly effective pain medications,” the doctors wrote.

“Guidelines and review articles have contributed to this perception by often uncritical extrapolation from FDA-approved indications to off-label use.”

Goodman and Brett say the wording in many medical guidelines “reinforces an inflated view of gabapentinoid effectiveness” by falsely claiming the drugs should be used to treat all types of nerve pain.

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“Another example is the 2016 guideline on opioid prescribing from the U.S. Centers for Disease Control and Prevention, which states broadly that gabapentin and pregabalin are first-line drugs for neuropathic pain, without further detail or specification,” they wrote. “Even for treatment of diabetic neuropathy (for which pregabalin is FDA approved and gabapentin is off-label), guideline conclusions tend to exaggerate effectiveness.”

Many patients who take gabapetinoids have side-effects such as dizziness or drowsiness, and there are an increasing number of reports that the drugs are being abused and sold on the street.   

Goodman and Brett have sounded the alarm before about the drugs, warning in a 2017 commentary in the The New England Journal of Medicine that “gabapentinoids are being prescribed excessively.”

They say doctors should do a better job warning patients about the side effects of gabapentinoids and the drugs should be stopped if a patient reports little or no benefit.  They also think medical guidelines should be revised to stop the promotion of gabapentinoids for any pain labeled as neuropathic.

Risky Combination: Opioids and Gabapentin

By Pat Anson, PNN Editor

Opioid medication significantly reduces low back pain, but opioids should not be used in combination with gabapentin (Neurontin) because of their limited effectiveness and potential for abuse, according to the authors of a small new study presented at the annual meeting of the American Academy of Pain Medicine.

"In these days, when we are focusing on reduction of opioids due to opioid crisis in the U.S., gabapentin could be an important part of multimodal non-opioid pain management," N. Nick Knezevic, MD, of the University of Illinois in Chicago told MedPage Today. "However, it should not be given to all patients since the effectiveness in chronic pain patients, particularly in those with low back pain, is limited."

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In a retrospective study, Knezevic and his colleagues looked at 156 patients with low back pain; half of whom were treated with opioids alone and the other half with a combination of opioids and gabapentin.

“According to our study, the combination of gabapentin with opioids was not statistically superior in providing pain relief, in contrast to opioids alone, in patients with chronic pain. Our results are in line with recent guidelines for low back pain treatment that reflect the need to assess the recommendation of gabapentinoids for chronic pain in patients already taking opiods to mitigate risk factors of abuse and overdose,” researchers found.

Gabapentin is an anticonvulsant that was originally developed as a treatment for epilepsy, but is now widely prescribed for a variety of chronic pain conditions. Its use in primary care as a treatment for chronic back and neck pain has risen by 535% in the last decade, despite little evidence of its effectiveness.

"The fact that anticonvulsants are often advertised to be effective for 'nerve pain' may mislead the prescriber to assume efficacy for low back pain or sciatica," Oliver Enke, MD, of the University of Sydney, told MedPage.

A 2018 study by Australian researchers found that gabapentinoids did not reduce back pain or disability and often had side effects such as drowsiness, dizziness and nausea. Another recent study found that combining gabapentin with opioid medication significantly raises the risk of dying from an overdose than opioid use alone.

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

The CDC’s opioid prescribing guideline recommends gabapentin as a safer alternative to opioids, without saying a word about its potential for abuse or side effects.

A 2017 commentary in the The New England Journal of Medicine warned that gabapentinoids -- a class of nerve medication that includes both gabapentin and pregabalin (Lyrica) -- are being overprescribed.

"We believe… that gabapentinoids are being prescribed excessively — partly in response to the opioid epidemic,” wrote Christopher Goodman, MD, and Allan Brett, MD. “We suspect that clinicians who are desperate for alternatives to opioids have lowered their threshold for prescribing gabapentinoids to patients with various types of acute, subacute, and chronic noncancer pain."

Can Gabapentin Improve Your Sex Life?

By Pat Anson, PNN Editor

Over the years the nerve drug gabapentin (Neurontin) has been used to treat a cornucopia of chronic pain conditions, from fibromyalgia and diabetic neuropathy to hot flashes and shingles.

Gabapentin is so widely prescribed that a Pfizer executive once called the drug “the snake oil of the twentieth century” because researchers found it successful in treating just about everything they studied.

Add sexual function to the list.

In a small study, researchers at Rutgers University found that gabapentin improved sexual desire, arousal and satisfaction in 89 women with provoked vulvodynia, a chronic condition characterized by stinging, burning and itching at the entry to the vagina. Vulvar pain often occurs during intercourse, which leads to loss of interest in sex.

The improvements in desire, arousal and sexual satisfaction were small, but considered “statistically significant” in research parlance. Gabapentin did not improve lubrication or orgasm.

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"Our theory was that reducing pelvic floor muscle pain might reduce vulvodynia pain overall and thus improve sexual function," said Gloria Bachmann, MD, director of the Women's Health Institute at Rutgers and lead author of the study published in the Journal of Obstetrics and Gynecology.

"We found that women with greater muscle pain responded better in terms of pain and improved arousal than those with less pain, which suggests that Gabapentin be considered for treatment in women who have significant muscle tightness and spasm in the pelvic region.”

Does this mean gabapentin is a female version of Viagra? Not necessarily, says Bachmann, who stressed that the study only focused on women with vulvodynia.

“We didn't research the question of gabapentin enhancing sexual function in all women,” Bachmann wrote in an email to PNN. “The decision to give gabapentin to a woman who reports chronic vulvar pain and sexual dysfunction would have to be made on an individual basis, depending on her medical history and the results of her physical and pelvic examination.

“From the data, it appears that women with increased muscle tenderness of the pelvic floor may be the group who benefit most from gabapentin.”

Sales of gabapentin have soared in recent years — not because it improves sexual satisfaction — but because it is seen as a safer pain reliever than opioid medication.

Patients prescribed gabapentin often complain of side effects such as mood swings, depression, dizziness, fatigue and drowsiness.  Drug abusers have also discovered that gabapentin can heighten the effects of heroin, cocaine and other illicit substances, and it is increasingly being abused.

Studies Warn of Pregabalin Deaths

By Pat Anson, Editor

Two new studies – one in Canada and one in Australia – should give pause to patients who use opioids and pregabalin (Lyrica), an anticonvulsant medication increasingly prescribed for fibromyalgia, neuropathy and other chronic pain conditions. Both studies found a number of overdose deaths that involve – but were not necessarily caused -- by pregabalin.

The Canadian study, published in the Annals of Internal Medicine, looked at over 1,400 patients in Ontario on opioid medication from 1997 to 2016 who died from opioid-related causes. Another group of over 5,000 surviving opioid patients was used as a control group.

Researchers found that patients who were co-prescribed opioids and pregabalin had a significantly higher risk of an overdose.

The risk of death was over two times higher for patients receiving opioids and a high dose of pregabalin (over 300mg) compared to those who took opioids alone.

Patients on a low or moderate dose of pregabalin also had a heightened risk, although not as large.

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Researchers say pregabalin has a sedative effect and may interact with opioids in ways that increase respiratory depression. Few doctors and patients are aware of the risk, even though over half of Ontario residents who begin pregabalin therapy are also prescribed an opioid.

"There is an important drug interaction between opioids and pregabalin that can lead to increased risk of fatal overdose, particularly at high doses of pregabalin," lead author Tara Gomes, PhD, of the Institute for Clinical Evaluative Sciences (ICES) and St. Michael's Hospital in Toronto, told MedPage Today.

"Clinicians should consider carefully whether to prescribe opioids and pregabalin together. If they decide that both medications are clinically appropriate, they should start with low doses and monitor their patients closely."

Lyrica (pregabalin) and Neurontin (gabapentin) are both made by Pfizer and belong to a class of anticonvulsant nerve medication called gabapentinoids. Sales of gabapentinoids have tripled in recent years, in part because of CDC prescribing guidelines that recommend the drugs as alternatives to opioid medication.  

U.S. health officials have only recently started looking into the misuse and abuse of gabapentinoids, which are increasingly used by addicts to enhance the euphoric effects of heroin and other illicit opioids. While gabapentin  has a warning label cautioning users who take the drug with opioids, there is no similar warning for pregabalin.

“Although current product monographs for gabapentin contain warnings about serious adverse events when this agent is combined with opioids, those for pregabalin do not. The importance of our finding warrants a revision of the pregabalin product monographs,” wrote Gomes.

Pregabalin Abuse in Australia

Health officials in Australia are also concerned about the growing use of pregabalin.  Researchers at the NSW Poisons Information Centre say poisoning cases involving pregabalin rose from zero in 2005 to 376 cases in 2016.

“Our study shows a clear correlation between the rapid and continuous rise of pregabalin dispensing and an increase in intentional poisonings and deaths associated with pregabalin,” said lead author Dr. Rose Cairns, a specialist at the NSW Poisons Information Centre.

According to the Australian Journal of Pharmacy (AJP), there have been 88 recorded deaths associated with pregabalin in recent years. Most of the deaths involved young, unemployed males who had a history of substance abuse, particularly with opioids, benzodiazepines, alcohol and illicit drugs.

“We believe that Australian doctors may not be aware of the abuse potential of pregabalin,” Cairns said. “Most patients who are prescribed this medication are in the older population but the group who are at high risk of overdosing are much younger. These people are likely to have been prescribed pregabalin despite having a history of substance abuse.”

According to researchers, up to two-thirds of people who intentionally misused pregabalin had a prior documented substance abuse history. “Prescribers need to consider this growing body of evidence that pregabalin has abuse potential before prescribing, especially to patients with substance abuse history,” said Cairns.

Pfizer did not respond to a request for comment on the Canadian and Australian studies.

Lyrica and Neurontin Ineffective for Low Back Pain

By Pat Anson, Editor

Lyrica, Neurontin and other anti-convulsant drugs are ineffective for treating low back pain and may even be harmful to patients, according to a new study published in the Canadian Medical Association Journal.

Prescriptions for anti-convulsant drugs have soared in recent years, as doctors seek “safer” alternatives to opioid pain medication.  Lyrica (pregabalin) and Neurontin (gabapentin) belong to a class of anti-convulsant nerve medications known as gabapentinoids. They are primarily used for treating nerve pain and fibromyalgia, but are increasingly being prescribed off-label to treat lower back and neck pain.

Australian researchers reviewed 9 placebo-controlled randomized trials and found high quality evidence that gabapentinoids did not reduce back pain or disability and often had side effects such as drowsiness, dizziness and nausea.

“The take-home message is that anti-convulsants are not effective and can lead to adverse effects in people with low back pain and radiating leg pain (eg, sciatica), so they should not be recommended to this patient population,” lead author Oliver Enke, MD, a researcher at the University of Sydney Medical School, told Helio Family Medicine.

Low back pain is the world’s leading cause of disability. Guidelines for treating low back pain usually recommend physical therapy, exercise and non-opioid pain relievers rather than stronger analgesics such as opioids or anti-convulsants.

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A 2017 study published in PLOS Medicine also warned that pregabalin and gabapentin were ineffective for low back pain and have a “significant risk of adverse effects.” 

PNN readers often complain about side effects from Lyrica and Neurontin.

“I have used both medicines and neither help with lower back pain for me,” said Sheri. “I will say the mental confusion and memory loss on Lyrica is very real, but it takes a slight edge of pain away in my body as a whole from the fibromyalgia.”

“I can vouch that Lyrica does not help with back pain,” said Debra. “It helped with the nerve pain but I thought I was literally losing my mind. I couldn't remember simple words or synonyms for words.”

“I've been taking gabapentin for almost six months; it has helped my peripheral neuropathy, but I still suffer every day from arthritis in every joint of my body, including my lower back,” another reader wrote.

Lyrica and Neurontin are both made by Pfizer and are two of the company’s top selling drugs, generating billions of dollars in sales annually. Lyrica is approved by the FDA to treat diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles, and spinal cord injuries.

Neurontin is approved by the FDA to treat epilepsy and neuropathic pain caused by shingles, but is also widely prescribed off-label to treat depression, ADHD, migraine, fibromyalgia and bipolar disorder. According to one estimate, over 90% of Neurontin sales are for off-label uses. About 68 million prescriptions were written for gabapentin in the U.S. last year, compared to 44 million in in 2013.

There have been increasing reports of gabapentinoids being abused by drug addicts, who have learned they can use the medications to heighten the high from heroin, marijuana, cocaine and other substances. Gabapentin is not currently scheduled as a controlled substance by the DEA, while pregabalin is classified as a Schedule V controlled substance, meaning it has a low potential for addiction and abuse.  

Growing Abuse of Gabapentin

By Christine Vestal, Stateline

Doctors who are cutting back on prescribing opioids increasingly are opting for gabapentin, a safer, non-narcotic drug recommended by the Centers for Disease Control and Prevention.

By doing so, they may be putting their opioid-using patients at even greater risk.

Recently, gabapentin has started showing up in a substantial number of overdose deaths in hard-hit Appalachian states. The neuropathic (nerve-related) pain reliever was involved in more than a third of Kentucky overdose deaths last year.

Drug users say gabapentin pills, known as “johnnies” or “gabbies,” which often sell for less than a dollar each, enhance the euphoric effects of heroin and when taken alone in high doses can produce a marijuana-like high.

Medical researchers stress that more study is needed to determine the role gabapentin may have played in recent overdose deaths. However, a study of heroin users in England and Wales published last fall concluded that combining opioids and gabapentin “potentially increases the risk of acute overdose death” by hampering breathing and reversing users’ tolerance to heroin and other powerful opioids.

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Kentucky last year classified gabapentin as a controlled substance, making it harder for doctors to prescribe it in copious quantities and for long durations. The new classification also allows police to arrest anyone who illicitly sells the drug, although the state’s drug control chief, Van Ingram, said that was not the intent of the new law.

In the last two years, Illinois, Ohio, Massachusetts, Minnesota, Tennessee, Virginia and Wyoming also have moved to control the flow of gabapentin by requiring doctors and pharmacists to check a prescription drug database before prescribing it to patients to make sure they aren’t already receiving gabapentin, or some other medication that interacts with it, from another physician.

In a statement to Stateline, Pfizer communications director Steven Danehy said, “Reports of misuse and abuse with this class of medicines are limited and typically involve patients with a prior history of substance abuse, including opioids.”

The drugmaker also pledged to “continue working with regulatory authorities and health officials to evaluate and monitor the safety of these medicines.”

Prescribed for Many Conditions

Approved by the FDA in 1993 for the treatment of epilepsy and the nerve pain associated with shingles, gabapentin is sold by Pfizer under the brand name Neurontin. A generic form of the drug has been available since 2004 and is now sold by several other companies as well.

Gabapentin is now one of the most popular prescription drugs in the United States, according to the New England Journal of Medicine. It was the 10th-most-prescribed medication in 2016. Its more expensive cousin, pregabalin, sold as Lyrica and also made by Pfizer, was the eighth best-selling.

Many doctors recommend gabapentin to patients for a long list of disorders, including hot flashes, migraines, restless leg syndrome, fibromyalgia, and neuropathic pain associated with diabetes and spinal injuries. Some doctors also prescribe it for anxiety and insomnia.

Now, research is underway to determine whether gabapentin may be effective as a treatment for alcoholism.

Already, it is widely used to ease the symptoms of drug and alcohol detoxification. And addiction specialists routinely use gabapentin to manage pain in people who are either addicted or at risk of addiction to opioids and other substances.

Alone, high doses of gabapentin have not been found to affect breathing. The vast majority of gabapentin deaths, about 4 in 5, also involved opioids, according to the journal Addiction.

People who stop taking the medication abruptly, however, can suffer withdrawal symptoms such as trembling, sweats and agitation.

In February, Food and Drug Administration director Scott Gottlieb said the agency was reviewing the misuse of gabapentin and, for now, had determined no action was necessary. Similarly, the CDC has not issued a warning about gabapentin, nor has the Drug Enforcement Administration.

(Editor's note: the CDC opioid guidelines recommend gabapentin without any mention of the risk of abuse or overdose associated with the drug, or of possible side effects such as weight gain, anxiety and mood disorders.)

Early Signs of Abuse

In Kentucky, Ingram said it has been clear to police and pharmacists for the last three or four years that gabapentin was becoming an increasingly popular street drug. “People were seeking early refills, claiming they lost their prescriptions and openly conducting transactions in parking lots outside of drug stores,” he said.

But since it wasn’t a controlled substance, nothing was done about it. That’s likely to start changing with the new law, he said.

“Misuse of gabapentin is just one more collateral effect of the opioid epidemic,” said Caleb Alexander, an epidemiologist at Johns Hopkins University who has been studying the heroin and prescription drug epidemic. When one drug becomes less available, drug users historically seek out alternatives, he said. “What is most surprising is the sheer magnitude of its use.”

The share of Appalachian drug users who reported using gabapentin to get high increased nearly 30-fold from 2008 to 2014, according to a 2015 study in the American Journal of Psychiatry.

Paul Earley, an addiction doctor practicing in Georgia and a board member of the American Society of Addiction Medicine, said, “We knew that a small subset of our addiction patients would abuse gabapentin.” But he said it wasn’t until 2016, when Ohio sounded an alarm about the drug’s association with overdose deaths, that addiction doctors started taking the problem more seriously.

“For years, we considered gabapentin to be ‘good for what ails you,’” Earley said. “But I’m much more cautious than I used to be. If there’s anything we’ve learned from the opioid epidemic, it’s that we need to rethink how we prescribe drugs we once assumed were safe.”

This is story is republished with permission by Stateline, an initiative of The Pew Charitable Trusts.

Should Gabapentin Be a Controlled Substance?

By Pat Anson, Editor

The U.S. Drug Enforcement Administration should consider scheduling gabapentin (Neurontin) as a controlled substance, according to researchers who studied the recreational use of the drug in Kentucky.

Gabapentin is a nerve medication approved by the Food and Drug Administration to treat epilepsy and post-herpetic neuralgia (shingles), but it is also widely prescribed off-label to treat fibromyalgia, migraines, neuropathy and other chronic pain conditions. The Centers for Disease Control and Prevention even recommends gabapentin as a safer alternative to opioids.

Sales of gabapentin have soared in recent years. About 64 million prescriptions were written for gabapentin in the U.S. in 20l6, a 49% increase in just five years.

But drug abusers have also discovered that gabapentin can heighten the effects of heroin, marijuana, cocaine and other substances.

"People are looking for other drugs to substitute for opioids, and gabapentin has filled that place for some," said Rachel Vickers Smith, PhD, an assistant professor at the University of Louisville School of Nursing. “Some have said it gives them a high similar to opioids. It had been easy to get a prescription for gabapentin and it's very cheap."

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Vickers Smith and her colleagues recruited 33 people from Appalachian Kentucky who used gabapentin recreationally and asked them about their drug use. Many reported they started taking gabapentin over 10 years earlier for a legitimate medical condition, such as pain and anxiety. Over time, they started using the drug to help them relax, sleep and get high.

“Focus group responses highlighted the low cost of gabapentin for the purpose of getting high and noted increasing popularity in the community, particularly over the last 2 years. Gabapentin was a prominent drug of abuse in two cohorts of the primarily opioid-using individuals. Providers should be aware of gabapentin’s abuse potential, and a reexamination of the need for scheduling is warranted,” researchers reported in the journal Psychology of Addictive Behaviors.

In 2017, Kentucky became the first state to classify gabapentin as a controlled substance, which makes it more difficult for the medication to be prescribed. Ohio’s Substance Abuse Monitoring Network also issued an alert warning of gabapentin misuse across the state.

‘Snake Oil of the 20th Century’

Gabapentin was first approved by the FDA in 1993 and sold by Pfizer under the brand name Neurontin. A few years later, it was so widely prescribed that a top Pfizer executive called gabapentin “the snake oil of the twentieth century” in an email. The company was later fined hundreds of millions of dollars for promoting Neurontin’s off-label use.

"Early on, it was assumed to have no abuse potential," says Vickers Smith. "There's a need to examine it in further detail, especially if prescribing it is going to be encouraged."

Federal health officials have only recently started looking into the misuse and abuse of gabapentinoids, a class of nerve medication that includes gabapentin and pregabalin (Lyrica).

"Our preliminary findings show that abuse of gabapentinoids doesn't yet appear to be widespread, but use continues to increase, especially for gabapentin," FDA commissioner Scott Gottlieb, MD, said last week at a conference on opioid prescribing. "We're concerned that abuse and misuse of these drugs may result in serious adverse events such as respiratory depression and death. We want to understand changes in how patients are using these medications."

Gottlieb said FDA investigators are looking at websites and social media where opioid users discuss their use of gabapentinoids.

"We know we need to investigate and respond to signs of abuse as soon as signals emerge. We need to get ahead of these problems," he said.

Gabapentin is not currently scheduled as a controlled substance by the DEA, while Lyrica is classified as a Schedule V controlled substance, meaning it has a low potential for addiction and abuse.  

Lyrica and Neurontin Use Triples

By Pat Anson, Editor

The use of gabapentin (Neurontin) and pregabalin (Lyrica) has soared in the United States, with little attention paid to their safety and effectiveness, according to a research letter published in JAMA Internal Medicine.

Gabapentin and pregabalin belong to a class of nerve medication known as gabapentinoids, which are increasingly prescribed as alternatives to opioids in treating neuropathy, fibromyalgia and other types of chronic pain.

In an analysis of health data for nearly 350,000 patients, researchers found that the use of gabapentinoids more than tripled in the past decade, from 1.2% of patients in 2002 to 3.9% in 2015.

Use of the drugs was concentrated in older patients with numerous other health problems, who were often co-prescribed opioids or benzodiazepines, a class of anti-anxiety medication.

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“The combination of a dearth of long-term safety data, small effect sizes, concern for increased risk of overdose in combination with opioid use, and high rates of off-label prescribing, which are associated with high rates of adverse effects, raises concern about the levels of gabapentinoid use,” wrote lead researcher Michael Johansen, MD, of OhioHealth, a large non-profit health system based in Ohio.

“While individual clinical scenarios can be challenging, caution should be advised in the use of gabapentinoids, particularly for those individuals who are long-term opioid users, given the lack of proven long-term efficacy and the known and unknown risks of gabapentinoid use.”

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Johansen’s research adds to a growing body of evidence that pregabalin and gabapentin are overprescribed and being abused. A recent study by Canadian researchers found that there was “no clear rationale” for the off-label use of the drugs and warned that they have a “significant risk of adverse effects” such as dizziness, fatigue and diminished mental activity.

Lyrica (pregabalin) and Neurontin (gabapentin) are both made by Pfizer and are two of the company’s top selling drugs, generating billions of dollars in annual sales. Lyrica is approved by the FDA to treat diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles and spinal cord injuries; while Neurontin is approved to treat epilepsy and post-herpetic neuralgia. Both drugs are also widely prescribed off label to treat back pain, depression, migraine and other conditions.

Sales of pregabalin and gabapentin have risen steadily in recent years, in part because of CDC prescribing guidelines that recommend the two drugs as alternatives to opioid pain medication. About 64 million prescriptions were written for gabapentin in the U.S. in 20l6, a 49% increase in just five years.

“We believe… that gabapentinoids are being prescribed excessively — partly in response to the opioid epidemic,” Christopher Goodman, MD, and Allan Brett, MD, recently wrote in a commentary published in The New England Journal of Medicine. “We suspect that clinicians who are desperate for alternatives to opioids have lowered their threshold for prescribing gabapentinoids to patients with various types of acute, subacute, and chronic noncancer pain.

Gabapentinoids are increasingly being used recreationally by addicts who have found the medications enhance the effects of heroin and other opioids. Lyrica and Neurontin have been linked to heroin overdoses in the United Kingdom, where prescriptions for both drugs have soared in recent years. 

Painkillers Raise Risk of Obesity and Hypertension

By Pat Anson, Editor

Commonly prescribed painkillers such as opioids and gabapentinoids  -- a class of pain medication that includes Lyrica and Neurontin – significantly raise the risk of obesity and high blood pressure, according to a large new study published in PLOS ONE.

British researchers analyzed health data on over 133,000 people, comparing the Body Mass Index (BMI), waist circumference, blood pressure and sleeping habits of patients taking pain relievers to those who did not. The study is believed to be the largest to look at the effects of painkillers on overall health.

“In the last two decades there has been a significant increase in the number of people being prescribed both opioid and non-opioid medications to treat chronic pain,” said lead author Sophie Cassidy, PhD,  a research associate at the Institute of Cellular Medicine, Newcastle University. “We already know that opiates are dependency-forming but this study also found patients taking opiates have the worst health. Obesity rates are much higher and the patients reported sleeping poorly.”

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Those taking opioids were 95% more likely to be obese, 82% more like to have a “very high” waist circumference and 63% more likely to have hypertension compared to the control group.  

“There could be a number of possible mechanisms by which opioids might be associated with weight gain. Sedation might decrease physical activity and therefore reduce energy expenditure, those in our cohort taking opiates were less active, and those taking both opiates and other sedative drugs were the least active. Opioids have also been shown to alter taste perception with a craving for sugar and sweet foods described,” Cassidy wrote.

“These results add further weight to calls for these chronic pain medications to be prescribed for shorter periods.”

Patients who took gabapentinoids were also more likely to be obese, have a bigger waist and higher blood pressure compared to those not taking the drugs.

Gabapentinoids are commonly prescribed as alternatives to opioids to treat neuropathy, shingles and fibromyalgia, although many patients complain about side effects such as weight gain, depression and anxiety.

As PNN has reported, gabapentinoids are also coming under scrutiny because they are increasingly being abused. Lyrica (pregabalin) and Neurontin (gabapentin) are being reclassified as controlled “Class C” substances in the UK, following a spike in the number of deaths involving the medications.

Last week, the West Virginia Board of Pharmacy designated gabapentin as a “drug of concern,” after overdoses in the state involving gabapentin rose from 36 deaths in 2012 to 106 in 2016.  Ohio, Pennsylvania and Kentucky have also reported increases in fatal overdoses involving gabapentin.