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.

Lyrica Not Effective for Treating Traumatic Nerve Pain

By Pat Anson, Editor

Pregabalin is not effective in relieving chronic pain caused by traumatic nerve injury, but it may be useful as an analgesic in treating pain after surgery, according to a new study published in the Journal of Neurology.

The placebo-controlled study followed 539 patients in North America, Europe, Africa and Asia for three months. About half had nerve pain after surgery, while the rest had nerve pain after an accident or trauma.

Researchers found that pregabalin was not an effective pain reliever for the patients with traumatic nerve injuries, but the drug did provide better pain relief than placebo for the surgery patients.

"While these finding show that pregabalin is not effective in controlling the long-term pain for traumatic injury, it may provide relief for patients (that) experience post-surgical pain," said lead author John Markman, MD, director of the Translational Pain Research Program in the University of Rochester Department of Neurosurgery.

"The possibility that there was pain relief for those patients who had a hernia repair, or breast surgery for cancer, or a joint replacement lays the groundwork for future studies in these post-surgical syndromes where there is so much need for non-opioid treatments."

Pregabalin, which is sold by Pfizer under the brand name Lyrica, is FDA-approved for the treatment of chronic pain associated with shingles, spinal cord injury, fibromyalgia, and diabetic peripheral neuropathy.

It is also commonly prescribed as an "off label" treatment for other types of chronic pain and as an alternative to opioid medication.

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A major challenge for doctors is that biological changes in nerves and other tissues while healing from surgery or trauma vary from one patient to the next. There is also no diagnostic method that allows doctors to identify which patients will respond to a particular type of pain treatment.

"Given the rising rates of surgery and shrinking reliance on opioids, it is critical that we understand how to study new drugs that work differently in patients like the ones included in this study," Markman added.

While critics often say there is little or no evidence to support the long-term use of opioids, the same is true for other types of pain medication, including pregabalin. Nevertheless, in its guideline for opioids, the Centers for Disease Control and Prevention recommends pregabalin and its chemical cousin gabapentin as alternatives for treating chronic pain – without even mentioning their side effects or potential for abuse.

Pregabalin and gabapentin belong to a class of nerve medication called gabapentinoids, which were originally developed to treat epilepsy, not pain. In recent, deaths involving gabapentinoids have increased in the UK, Australia and Canada, where some addicts have learned the drugs can heighten the euphoric effect of heroin and other opioids.

The use of pregabalin and gabapentin has tripled in the U.S. over the past decade, but health officials have only recently started looking into their misuse and abuse. While gabapentin has a warning label cautioning users who take the drug with opioids, there is no similar warning for pregabalin.

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.  

FDA Monitors Social Media for Drug Abuse Trends

By Pat Anson, Editor

A recent letter in The New England Journal of Medicine sheds some light on how the Food and Drug Administration tracks changing patterns of drug use on Facebook, Twitter and other social media.

The FDA began monitoring social media – what it calls “proactive pharmacovigilance” – about a decade ago, primarily as an early warning system for adverse events involving medication.

More recently, the agency has used active surveillance of social media to study the abuse of opioid painkillers and gabapentinoids, a class of nerve medication that includes gabapentin (Neurontin) and pregabalin (Lyrica). Gabapentinoids are increasingly being prescribed as “safer” alternatives to opioids.

“To understand why usage patterns are shifting, the FDA used a social media ‘listening platform’ to set up a dashboard to track traditional social media sites (such as Twitter, Facebook, Instagram, blogs, and forums) that we monitor for conversations about opioids,” explained FDA commissioner Scott Gottlieb, MD, and co-authors Douglas Throckmorton, MD, and Janet Woodcock, MD, two senior FDA officials.

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“When we find mention of additional substances on social media or elsewhere, we conduct more specific searches for relevant, publicly available conversations through our listening platform, as well as through Reddit, Google, and various online forums that don’t require registration or subscription. These may include forums associated with drug misuse or abuse, such as Bluelight.org and talk.drugabuse.com.”

What did the FDA learn about gabapentinoids on social media? Preliminary findings indicate the abuse of gabapentinoids isn’t widespread, but their use continues to increase, especially for gabapentin.

The FDA is also actively monitoring the social media sites of kratom vendors. As PNN reported last month, one vendor received a warning letter from the FDA for sharing on its Facebook page a CNN story about the herbal supplement as a possible treatment for pain and opioid addiction. The vendor only said the story was “positive news for kratom,” but the FDA said that amounted to the illegal marketing of an unapproved drug.

“The FDA thus faces challenges as we confront the opioid crisis and monitor changing patterns of use, abuse, and misuse of other products,” Gottlieb wrote. “The right approach to regulating these substances is best determined through a multifaceted system of pharmacovigilance, using various tools to mine traditional and new sources of epidemiologic data, assess products’ pharmacologic properties, and evaluate the social contexts in which substances are being used.”

To be clear, the FDA’s surveillance of social media isn’t very different from what private enterprise is already doing. NUVI, for example, provide social media monitoring to companies “to get real-time insights into what people are saying about your brand online.”  Companies also sell software that track keywords, hashtags and user profiles on social media. And PatientsLikeMe, the largest online patient network with over 600,000 members, sells some of its data to the FDA and healthcare industry.

At PNN, we do stories all the time about opioids, kratom, gabapentinoids and other drugs. Is Pain News Network under surveillance by the FDA? Are reader comments on our website and social media being monitored? We don’t know. But in an age of growing concern about Internet privacy and the sharing of personal data, we thought you should know that the answer could be yes.

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. 

FDA Approves Extended-Release Lyrica

By Pat Anson, Editor

The U.S. Food and Drug Administration has approved a new extended-release version of Lyrica for the treatment of neuropathic pain. Lyrica CR is designed to be taken once a day, instead of the two or three doses recommended for Lyrica’s original formulation.

“Lyrica CR was developed to offer patients an effective treatment option with the convenience of once-daily dosing,” said James Rusnak, MD, Chief Development Officer in Pfizer’s Global Product Development. “It provides an important option for patients and health care providers managing these often debilitating pain conditions.”

Pfizer said the effectiveness of Lyrica CR was established in a clinical trial of over 800 patients with neuropathic pain. Patients who took Lyrica CR had a 74% reduction in pain, compared to about 55% who took a placebo. The most common side effects of Lyrica CR were dizziness, somnolence, headache, fatigue, peripheral edema, nausea, blurred vision, dry mouth and weight gain.

Lyrica (pregabalin) is one of Pfizer’s top selling drugs, but the company will likely face strong competition from cheaper generic versions of pregabalin when its U.S. patent expires next year.

Pfizer is undoubtedly hoping that current Lyrica users will switch over to the new extended release version, which will have full patent protection for many years to come. The company did not release any information on the cost of the new drug, which is expected to be available in January.

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Unlike the original formulation of Lyrica, which is widely prescribed to treat fibromyalgia, Lyrica CR is only approved to treat nerve pain caused by diabetic peripheral neuropathy and postherpetic neuralgia caused by shingles. But that won’t stop doctors from prescribing it off-label to fibromyalgia and other chronic pain conditions.

Pregabalin Under Scrutiny

The extended release version of Lyrica comes at a time when pregabalin is drawing new scrutiny from researchers and doctors who believe the medication is over-prescribed and being abused. Pregabalin belongs to a class of nerve drug known as gabapentinoids, which are increasingly being prescribed as alternatives to opioid pain medication.

 “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.”

As PNN has reported, the World Health Organization and the FDA are also investigating reports that pregabalin is being abused. Addicts have learned pregabalin enhances the effects of heroin and other opioids.

“Reports indicate that patients are self-administering higher than recommended doses to achieve euphoria, especially patients who have a history of substance abuse, particularly opioids, and psychiatric illness. While effects of excessively high doses are generally non-lethal, gabapentinoids such as pregabalin are increasingly being identified in post-mortem toxicology analyses,” the FDA said in a recent notice published in the Federal Register.

The warning label for Lyrica CR will caution users that the drug can be abused.

“Patients should not drink alcohol while taking Lyrica CR. Patients may have more dizziness and sleepiness if taking Lyrica CR with alcohol, narcotic pain medicines, or medicines for anxiety. Patients who have had a drug or alcohol problem may be more likely to misuse Lyrica CR,” the label warns.

Pregabalin is classified as Schedule V controlled substance in the U.S., which means it has a low potential for abuse.

Gabapentin Raises Risk of Opioid Overdose

By Pat Anson, Editor

Another study is raising questions about the safety of the anti-seizure drug gabapentin, especially when it’s taken with opioid pain medication.

According to research published online in PLOS Medicine, combining gabapentin with opioid painkillers is associated with a significantly higher risk of dying from an opioid overdose than opioid use alone.

"Clinicians should consider carefully whether to continue prescribing this combination of products, and when deemed necessary, should closely monitor their patients and adjust opioid dose accordingly," wrote lead author Tara Gomes, PhD, principal investigator for the Ontario Drug Policy Research Network and an assistant professor at the University of Toronto.

Gomes and her colleagues analyzed data from 1,256 people in Ontario, Canada who died from opioid-related causes, and compared them with a control group of 4,619 people who also used opioid medication, but did not die of an opioid-related cause.

Overall, 12.3% of the people who died and 6.8% in the control group were prescribed gabapentin in the prior 120 days. After adjusting for additional risk factors, the researchers estimated that the combination of gabapentin and opioids was associated with a 49% higher risk of dying from an opioid overdose.

Although gabapentin is an anticonvulsant originally developed as a treatment for epilepsy, it is now widely prescribed for neuropathy and other chronic pain conditions, sometimes in combination with opioids.

Until now, no previous study had examined the risks of using gabapentin and opioid medication simultaneously, even though both are known to cause respiratory depression that can lead to an overdose.

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“Our study has important implications for public health, particularly given the high degree of co-prescription. Almost 10% of patients treated with an opioid in our study also used gabapentin, while nearly half of patients treated with gabapentin were co-prescribed opioids,” said Gomes.

“Gabapentin is frequently used as an adjunct to opioids for neuropathic pain syndromes, but physicians may not be aware of the potential for respiratory depression with this drug; thus, increased awareness among patients and clinicians about the potential for a life-threatening interaction between these drugs is essential.”

The researchers believe pregabalin, an anticonvulsant that acts similarly to gabapentin, may also raise the risk of overdose when taken with opioids. But they were unable to test their theory because of the limited use of pregabalin during the study period.

Both pregabalin and gabapentin are produced by Pfizer -- under the brand names Lyrica and Neurontin -- and are two of its top selling drugs. Pfizer did not respond to a request for comment on the Canadian study.

A previous study linked pregabalin and gabapentin to an uptick in opioid overdoses in England and Wales. Some addicts believe the drugs can boost the “high” they get from heroin and other illicit substances.

Gabapentin is approved by the FDA to treat epilepsy and neuropathic pain caused by shingles. It is also prescribed “off-label” for depression, migraine, fibromyalgia and bipolar disorder. About 64 million prescriptions were written for gabapentin in the U.S. in 2016, a 49% increase since 2011.

Pregabalin is approved by the FDA to treat diabetic nerve pain, fibromyalgia, epilepsy, post-herpetic neuralgia caused by shingles and spinal cord injury. It is also prescribed off label to treat a variety of other conditions.

The CDC’s opioid prescribing guidelines recommend both pregabalin and gabapentin as alternatives to opioids, without saying a word about their potential for abuse or side effects. Pfizer has signed agreements with local prosecutors in Chicago and Santa Clara County, California to support the CDC guidelines and withdraw funding from patient advocacy groups and non-profits that question their validity.   

A recent commentary in the The New England Journal of Medicine warned that gabapentinoids -- the class of medication that Neurontin and Lyrica belong to -- 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."