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.  

Study Finds Little Evidence Shock Therapy Works

By Pat Anson, Editor

There is little evidence that electric shock therapy is an effective treatment for fibromyalgia, headache, degenerative joint pain and other chronic pain conditions, according to a new study by researchers at the Department of Veterans Affairs.

Cranial electric stimulation (CES) uses electrodes placed on the head to send small electric shocks to the brain to stimulate neurotransmitters.  Consumer interest in the therapy is increasing and several manufacturers make portable CES devices for home use -- such as the Fisher Wallace stimulator and Alpha-Stim AID -- marketing them as a treatment for pain, depression, anxiety and insomnia.

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But in a review of 26 clinical trials published in the Annals of Internal Medicine, researchers found “limited evidence” to support the use of CES to treat these medical conditions. Many of the studies were small, had questionable validity and the reported results were often inconsistent. Some studies suggested that CES therapy could help patients with depression and anxiety, but the VA researchers say better studies were needed to prove it.

“The evidence for the effectiveness and safety of CES is sparse. Low-strength evidence suggests a beneficial association in patients with anxiety and depression. The intervention is probably safe, but strength of evidence is low,” wrote lead author Paul Shekelle, MD, of the West Los Angeles Veterans Affairs Medical Center.

In an editorial also published in the journal, a physician who uses CES therapy on his patients called the study findings “disappointing,” but said he and his colleagues would probably keep using the devices.

“I am not sure what my hospital will do with the information from this review. I know I will be less enthusiastic about recommending CES; however, I doubt that we will stop using it,” wrote Wayne Jonas, MD, of Samueli Integrative Health Programs in Alexandria, VA.

“When one of my patients, who had chronic pain, depression, and insomnia, finished her first CES treatment, she said she loved it. ‘I felt really relaxed,’ she said. ‘Can I have one of these at home?’ Our policy is to have patients try the treatment in the clinic at least 3 times. If it improves pain, depression, or insomnia, the patient can apply to get a home machine.”

The Food and Drug Administration first approved the use of CES in 1978 to treat depression, anxiety and insomnia. Because of that initial approval, the CES devices on the market today have not been required to prove their safety and effectiveness. The devices can be easily purchased online, but a prescription is required in the U.S.

Fibromyalgia Linked to Overactive Brain Networks

By Pat Anson, Editor

Many fibromyalgia sufferers have been told that the pain is “all in their head.” New research indicates there may be some truth to that, and that overactive brain networks could play a role in the hypersensitivity of fibromyalgia patients.

Fibromyalgia is a poorly understood disorder characterized by deep tissue pain, fatigue, headaches, mood swings and insomnia. There is no known cause and successful treatments have been elusive.

In a lengthy study published in the journal Scientific Reports, an international team of researchers at the University of Michigan and in South Korea report that patients with fibromyalgia have brain networks primed for rapid responses to minor changes. This abnormal hypersensitivity is known as called explosive synchronization (ES).

"For the first time, this research shows that the hypersensitivity experienced by chronic pain patients may result from hypersensitive brain networks," says co-senior author Richard Harris, PhD, an associate professor of anesthesiology at Michigan Medicine’s Chronic Pain and Fatigue Research Center.

In ES, a small stimulus can lead to a dramatic synchronized reaction throughout the network, as can happen when a power outage triggers a major grid failure or blackout. Until recently, this phenomenon was studied in physics rather than medicine. Researchers say it's a promising avenue to explore in the quest to determine how a person develops fibromyalgia.

"As opposed to the normal process of gradually linking up different centers in the brain after a stimulus, chronic pain patients have conditions that predispose them to linking up in an abrupt, explosive manner," says first author UnCheol Lee, PhD., a physicist and assistant professor of anesthesiology at Michigan Medicine.

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The researchers tested their theory by conducting electroencephalogram (EEG) tests on the brains of 10 female patients with fibromyalgia. Baseline EEG results showed the patients had hypersensitive brain networks, and that there was a strong correlation between the degree of ES conditions and the self-reported intensity of their pain during EEG testing.

Lee's research team and collaborators in South Korea then used computer models of brain activity to compare the stimulus responses of the fibromyalgia patients to those of healthy ones. As expected, the fibromyalgia model was more sensitive to electrical stimulation.

"We again see the chronic pain brain is electrically unstable and sensitive," Harris says.

Harris says this type of modeling could help guide future treatments for fibromyalgia. Since ES can be modeled outside of the brain in computers, researchers can test for influential regions that transform a hypersensitive network into a more stable one. These regions could then be targeted in living humans using noninvasive brain modulation therapies such as transcranial magnetic stimulation, which is currently used to treat fibromyalgia and depression.

“We expect that our study may ultimately suggest new approaches for analgesic treatments. ES provides a theoretical framework and quantitative approach to test interventions that shift a hypersensitive brain network to a more normal brain network,” researchers reported. 

“It may be possible to convert an ES network to a non-ES network just by modulating one or two hub nodes. Indeed, transcranial magnetic stimulation and/or transcranial direct current stimulation may be improved by ‘targeting’ these sensitive hub nodes. The application of deep brain stimulation to critical nodes that could modify ES conditions is another therapeutic possibility that could be explored.”

The research was funded by the Cerephex Corporation, James S. McDonnell Foundation, and the National Institutes of Health

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.”

JAMA INTERNAL MEDICINE

JAMA INTERNAL MEDICINE

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.

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.

A Pained Life: It Never Hurts to Ask

By Carol Levy, Columnist

Recently a documentary was released on Netflix about Lady Gaga.  A part of her story is that she has fibromyalgia. 

I have not seen the film, but understand she devotes a little time to detailing and showing how she deals with chronic pain, both physicially and emotionally. Articles and posts abound in chronic pain social media about the film and Lady Gaga's pain.

The odd thing is many of the writers start by complaining that people don’t understand their pain, why they have to take drugs, and why they can't do many things that seem so easy to everyone else. 

Then, strangely, they do exactly what they complain happens to them.  They express doubts about Lady Gaga’s diagnosis, wonder if she is malingering, and say she can't really have fibro because her level of suffering and disability is not the same as theirs.

It seems we in the chronic pain community want to have our cake and eat it, too.  We want to have the discussion about chronic pain made public. We want awareness. But the awareness has to be exactly the way we want it or we don't want it at all

SCENE FROM "GAGA: FIVE FOOT TWO"

SCENE FROM "GAGA: FIVE FOOT TWO"

Many in the pain community express feelings that anything in the public eye that even hints of chronic pain should be about the person's struggles and life interruptions caused by pain.  Lady Gaga is a case in point. 

“She didn’t talk enough about fibro,” writes one person, others echoing the sentiment. “I thought from all the hype I heard it was going to be about that.” 

It would have been terrific if Lady Gaga had devoted more time to her disease and its effects on her life, but then that really was not the point of the documentary.

“Some of the film may actually be hurtful to some of us, as it shows her being able to do very physical things that are often beyond many of us as we struggle with the pain. If you have watched her perform she is not a sedentary singer,” wrote one poster on social media.  

Maybe it is worth asking her. Could you do something more, maybe another film or even just a commercial, that would bring needed attention to chronic pain and its effects on our lives?  

Last month was Pain Awareness Month, and it went by with almost no awareness or notice at all.  Lady Gaga might be the awareness hook that we need.

But we need to stop lamenting, hoping and complaining that no one is doing enough.  It is past time to take the bull by the horns.  We have to do it ourselves.  As they say, if not now, when? If not us, who?

And who knows? If someone or a bunch of someones ask Lady Gaga or another celebrity to be our voice, they might actually respond. If we don't ask, we’ll never know if they want to help the pain community.

The worst they can say is no.  And maybe, just maybe, we can get a “Yes.”

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Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.” 

Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.