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.

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.

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.

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.

Breakthrough Blood Test Shows the ‘Color of Pain’

By Steve Weakley

A revolutionary new blood test developed by Australian researchers could give doctors instant insight into the severity of chronic pain by identifying colored biomarkers in the blood.  The “painHS” test uses advanced light spectrum analysis to identify the molecular structure of pain in immune cells.

“We are literally quantifying the color of pain,” explains neuroscientist Mark Hutchinson, PhD, a professor at the University of Adelaide Medical School in Australia.  “We’ve now discovered that we can use the natural color of biology to predict the severity of pain. What we’ve found is that persistent chronic pain has a different natural color in immune cells than in a situation where there isn’t persistent pain.”

Hutchinson and his colleagues discovered molecular changes in the immune cells of chronic pain patients. These pain biomarkers can be instantly identified through hyperspectral imaging, giving doctors the ability to measure a patient’s pain tolerance and sensitivity.

The test could potentially provide physicians with the first biology-based test to measure pain as the “5th vital sign” and to justify prescribing pain medication or other therapies.

Hutchinson was quick to point out that the test is not intended replace a patient’s description of pain to their physician.  Pain is subjective and varies from patient to patient, depending on their medical condition and many other factors.  Current tests used to measure pain in adults, such as the sad and smiley faces of the Wong-Baker pain scale, are so simple they were initially developed for young children.

“Self-reporting (by patients) is still going to be key but what this does mean is that those ‘forgotten people’ who are unable to communicate their pain conditions such as babies or people with dementia can now have their condition diagnosed and treated,” said Hutchinson, who believes the test could also revolutionize pain treatment in animals.

“Animals can’t tell us if they’re in pain but here we have a Dr. Doolittle type test that enables us to ‘talk’ to the animals so we can find out if they are experiencing pain and then we can help them."

Hutchinson says the test could also help speed the development of new drugs that could target particular kinds of chronic pain, and could eliminate the need for placebos in clinical trials by giving an instant indicator of a treatment’s effectiveness.

“We now know there is a peripheral cell signal, so we could start designing new types of drugs for new types of cellular therapies that target the peripheral immune system to tackle central nervous system pain,” he explained.

Hutchinson thinks the “painHS” test could be widely available to pain specialists and general practitioners in as little as 18 months and could provide a cost-effective tool to measure the severity of pain in patients with back problems, cancer, fibromyalgia, migraines and other conditions.

Several other blood tests have already been developed to diagnose patients with specific chronic pain conditions such as fibromyalgia.

IQuity Labs recently introduced a blood test that can identify fibromyalgia by analyzing ribonucleic acid (RNA) in blood molecules. EpicGenetics launched the first fibromyalgia blood test in 2013. That test looks for chemokines and cytokines, which are protein molecules produced by white blood cells.

New Blood Test Launched for Fibromyalgia

By Pat Anson, Editor

A Tennessee laboratory has launched an innovative new blood test that uses RNA analysis to diagnose patients with fibromyalgia. IQuityLabs says its test – called IsolateFibromyalgia – can identify fibromyalgia within a week and with over 90 percent accuracy. The test costs $599.

Ribonucleic acid (RNA) is a molecule that plays an essential role in sensing and communicating responses to cellular signals. Unlike DNA tests, which can only predict the likelihood of someone having a disease, RNA tests show what is actually happening at a cellular level. 

IMAGE COURTESY OF IQUITY

“When we look at RNA in blood, we’re looking at a snapshot of what’s actually taking place at that moment inside the patient’s blood cells,” explained Chase Spurlock, CEO of IQuity. “Using that information, we can decipher those molecular communication patterns, those RNA signals that are taking place, and figure out does it look like fibromyalgia syndrome or does it look like something else?

“In the case of fibromyalgia, we completed our clinical validation studies and our accuracy is at 94 percent and the sensitivity and specificity are greater than 90 percent as well. So, it’s a highly actionable test.” 

The National Institutes of Health estimates that about 5 million Americans suffer from fibromyalgia, a poorly understood disorder characterized by deep tissue pain, fatigue, headaches, mood swings and insomnia. It often takes years for a patient to be diagnosed with fibromyalgia and some doctors still refuse to recognize it as a disease.

In 2013, California-based EpicGenetics launched the first fibromyalgia blood test. The FM/a test looks for chemokines and cytokines, which are protein molecules produced by white blood cells. Fibromyalgia patients have fewer chemokines and cytokines than healthy people, according to EpicGenetics, and have weaker immune systems as a result. Critics say the FM/a test is unreliable and the same molecule levels can be found in people with other disorders, such as rheumatoid arthritis.

Spurlock says RNA testing is more specific and accurate than DNA or other blood tests used to diagnose autoimmune conditions. 

“I think what this test will do is allow for clarity and efficiency in the provider-patient relationship,” he said. “Once we receive the blood samples here, our lab technicians process the sample and we report the result back within a week.” 

Last year IQuity launched blood tests to diagnose multiple sclerosis and irritable bowel syndrome (IBS). It hopes to further develop the science to diagnose other autoimmune disorders.

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."

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.

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.

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.

“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

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.”

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.

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"

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.”

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.

9 Holistic Approaches to Relieve Joint Pain

By Nicole Noel, Guest Columnist

Whatever your ailment may be, holistic medicine has an answer.

A therapeutic method that dates back to early civilizations, holistic medicine takes into account the mind, body, emotions and spirit -- with the aim of helping patients achieve or restore proper balance in life and prevent or heal a range of conditions, including musculoskeletal pain. Holistic treatments offer a ray of hope for many patients suffering from arthritis, osteoporosis, fibromyalgia and other conditions that cause joint pain.

Not all alternative medicine is created equal, and some natural healing methods will produce better and quicker results. If you want to treat arthritis and other joint aches with holistic treatments, here are a few natural pain relievers you can try.

1. Tai Chi

A low-impact activity that can increase range of motion and strengthen joints and surrounding muscle tissue, tai chi is an ancient physical and spiritual practice that can help arthritis patients soldier through their pain.

According to a 2013 study, tai chi can relieve pain, stiffness, and other side-effects of osteoarthritis. In addition to pain relief, tai chi can help improve range of motion and alleviate joint pain for people living with fibromyalgia and rheumatoid arthritis.

2. Yoga

Another ancient technique which promotes natural healing, yoga is perfect for individuals suffering from lower back and joint pain. Gentle stretches and poses opening the joints can help prevent and alleviate chronic soreness in the shoulders, hips, and knees.

A form of yoga called mudras utilizes a series of hand gestures to increase energy, and improve mood and concentration.

3. Massage

An invigorating massage with warm essential oil can help many conditions, and joint pain is one of them.

By enhancing blood flow, relaxing the muscle tissue and soothing inflammation, a well-timed massage can ease joint stiffness and increase range of motion in individuals suffering from arthritis, fibromyalgia, and osteoporosis.

4. Acupuncture

A 2013 review of medical studies has shown that acupuncture can help relieve musculoskeletal pain caused by fibromyalgia. By activating the body’s natural pain relief system and stimulating the nerves, muscles and connective tissue, acupuncture can relieve joint aches for people who are resistant to other holistic pain relief techniques.

A 2010 study found that acupuncture can also be a beneficial for peripheral joint osteoarthritis.

5. Diet Changes

An apple a day may or may not keep the doctor away, but a custom-tailored diet can help you with joint pain. Nutritional tweaks can begin with increased intake of chondroitin sulfate, glucosamine, and Omega 3 fatty acids, which can reduce joint pain in arthritis and osteoporosis patients.

To ease joint problems, your pantry should be stocked with foods that promote healing and reduce inflammation, such as onions, carrots, and flaxseed. Herbs and spices such as turmeric (curcumin) and cayenne pepper can also help with pain relief.

6. Aromatherapy

If you think pain relief can’t smell good, you’re mistaken. Studies have shown that peppermint and eucalyptus oil can reduce swelling, pain and discomfort in patients with inflamed joints. For joint soreness and stiffness caused by arthritis, aromatherapy experts recommend regular application of myrrh, turmeric, orange, or frankincense oil to ease inflammation and pain, and to increase range of motion.

You can also combine aromatherapy with heat and cold treatments.  Be sure to keep the tender joints elevated during treatment to reduce swelling.

7. Spa Treatments

Few things can beat the appeal of a full-scale spa experience. If you’re suffering from knee, hip, shoulder or elbow pain and other holistic methods haven’t helped, try balneotherapy, which combines aqua massage with deep soaks in heated mineral water and medicinal mud baths.

One study found that balneotherapy significantly reduced knee and back pain in older adults.

8. Aquatic Sports

If you don’t want to immerse yourself in mud, you can supplement your holistic pain therapy with water aerobics, swimming, aqua jogging or aqua spinning. According to a 2014 study, water exercises can ease pain and improve joint function for osteoarthritis patients.

Additionally, a 2015 study found that aquatic circuit training can help relieve knee pain in cases of progressed osteoarthritis.

9. Capsaicin cream

Another natural treatment for joint pain and stiffness is homemade capsaicin cream, which can help reduce swelling and increase range of motion. To stay on the safe side, you should be careful when handling hot peppers when preparing the cream, and avoid using it on sensitive and damaged skin.

As our bodies age, joint pain can become a chronic. If you don’t want to take your chances with conventional pharmaceuticals, you can always turn to holistic medicine for answers and help. When musculoskeletal pain hits home, one or more of these holistic treatments can help.

Nicole Noel is a lifestyle blogger who is passionate about yoga and healthy living. She enjoys sharing her experiences and ideas on how to lead a happy and healthy life. If you want to read more from Nicole, you can find her on Twitter and Facebook.

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.

Can Analgesic Creams Treat Chronic Pain?

By Pat Anson, Editor

An Irish opera singer who suffered from the same chronic pain condition as Lady Gaga claims she was “cured” of fibromyalgia by rubbing a topical cream on her body.

“I was amazed that within a few hours of putting the cream on my knees and my neck, the pain started to ease and the swelling abated slightly,” Liz Farrell told the Daily Mail. “By the end of the first week I was able to start reducing my daily intake of painkillers.”

Farrell was diagnosed six years ago with fibromyalgia – a condition that causes widespread body pain, fatigue and insomnia. The 40-year old singer tried a cocktail of drugs that included tramadol, Cymbalta, Lyrica and anti-inflammatory medications, but her pain only grew worse and she stopped performing.

Then Farrell started using Celafen, a drug-free topical cream that contains menthol, Vitamin E and a patented blend of fatty acids called Celadrin, which lubricates cell membranes and has anti-inflammatory properties.

“I felt completely normal again, like my old self. I was able to start driving again, which I’d not been able to do for two years,” said Farrell, who recently started performing again. “It has been like coming to the end of a prison sentence, to have that freedom back again.” 

"I can’t begin to imagine how Lady Gaga has been coping with her stage performances with this crippling condition; she must be a very brave lady.”

Lady Gaga’s battle with chronic pain has received a great deal of media coverage lately. She recently cancelled concert appearances in Brazil and Europe to focus on her health.

Would Celadrin help Lady Gaga? Would it help you? The reviews online are a bit mixed.

“Celadrin works very well for me. I've been dealing with a shoulder injury for about six months, and I have tried almost every pain control cream and gel on the market. This is one of the best I've found,” said one reviewer.

“I'm using it on a painful knee and surrounding muscles and ligaments,” another reviewer wrote. “I was really hoping this cream would provide relief. I need to take pain pills so I can walk so I'm not sure how much this cream really helps.”

“It is truly amazing how it takes away all my aches & pains. I suffer from disc issues - cervical to lumbar area. I get referred pain in my upper arms from my cervical disc issues. I rub this on and instantly I feel so much comfort,” a woman wrote.

“Expensive. Smelly and doesn't do a thing,” said another. 

Whether it works or not, it’s fairly cheap. Celafen cream is sold online in the U.K. for £9.95 – or $11.65. You can also buy Celadrin in various formulations on Amazon for about the same price.

Study Finds Analgesic Creams Effective

Topical analgesic creams are mostly used to treat acute pain in sore muscles and joints – not the intractable pain that comes from severe chronic illness. But a new study published in the Journal of Pain Research suggests that creams are effective and could be safer than opioids and other prescription drugs in managing chronic pain.

In the observational study of 631 patients with moderately severe chronic pain, Clarity Science researchers found significant decreases in pain in patients who used generic analgesic creams daily for 3 to 6 months. Most of the creams contained diclofenac, ketoprofen or flurbiprofen, non-steroidal anti-inflammatory drugs (NSAIDS) that were combined with other neuropathic agents.

"The study is important in that existing topical analgesics that have lost big Pharma interest have been found not only to have a profound therapeutic effect, but also offer a safe and effective alternative to opioids," Dennis Harris, MD, Clarity's Chief Medical Officer said in a press release. “New and experimental drugs are not always the answer to current issues."

Researchers say 54% of treated patients in the 3-month group and 60% of treated patients in the 6-month group reduced their use of pain medications. Over half the patients who were not treated with analgesic creams increased their use of pain medication.

Treated patients also reported a preference for topical treatments and only a few had side effects.

"The results of this study show that topical analgesics were associated with reductions of up to 60% in the use of concurrent pain medications, including oral opioid analgesics,” said Jeffrey Gudin, MD, lead investigator of the study and the Director of Pain and Palliative Care at Englewood Hospital in New Jersey.

“Topical agents have the potential to provide analgesic effects without the risk of abuse, misuse, and addiction or systemic adverse events (AEs) associated with oral analgesics. Also, they lower the risk of systemic AEs and drug-drug interactions, have limited systemic absorption, offer simple-dose determination, provide direct access to the target site, and are easy for patients to apply."

For the record, Dr. Gudin was paid to participate in the Clarity Science study. Gudin is a popular speaker at pain management conferences and last year received nearly $280,000 in speaking and consulting fees from opioid manufacturers and other drug makers. Clarity Science received funding for the study from several independent specialty pharmacies that sell analgesic creams.

Lady Gaga Denies ‘Making Up’ Her Chronic Pain

By Pat Anson, Editor

Lady Gaga has postponed the European leg of her “Joanne” concert tour, announcing in an Instagram post that “trauma and chronic pain have changed my life” and would keep her from performing for several weeks.

Last week the 31-year old entertainer also canceled a concert appearance in Brazil and revealed for the first time that she suffers from fibromyalgia.

“Lady Gaga is suffering from severe physical pain that has impacted her ability to perform," tour promoter Live Nation said in a statement. "She remains under the care of expert medical professionals who recommended the postponement."

Some critics have questioned the severity of Lady Gaga’s pain, claiming she used it as an excuse to postpone her tour or as a publicity stunt to promote “Gaga: Five Foot Two,” a Netflix documentary that shows her being treated for chronic pain.

scene from "gaga: five foot two"

Lady Gaga responded to the criticism with the lengthy post on Instagram.

“As I get stronger and when I feel ready, I will tell my story in more depth, and plan to take this on strongly so I can not only raise awareness, but expand research for others who suffer as I do,” she wrote.

“I use the word ‘suffer’ not for pity, or attention, and have been disappointed to see people online suggest that I'm being dramatic, making this up, or playing the victim to get out of touring. If you knew me, you would know this couldn't be further from the truth. I'm a fighter. I use the word suffer not only because trauma and chronic pain have changed my life, but because they are keeping me from living a normal life. They are also keeping me from what I love the most in the world: performing for my fans.”

The Live Nation statement said Lady Gaga would “spend the next seven weeks proactively working with her doctors.”  

The singer's European concerts were scheduled to begin Thursday in Barcelona, Spain and run through the end of October.  Fans were told to keep their tickets until the concerts were rescheduled.  Lady Gaga is still scheduled to perform during the second leg of her North American tour, which begins November 5 in Indianapolis.

Fibromyalgia is a poorly understood disorder characterized by deep tissue pain, fatigue, depression and insomnia. As many as 90 percent of fibromyalgia cases are diagnosed in women.

Lady Gaga also has chronic hip pain from synovitis, an inflammation of the joint that can be caused by overuse or injury. Her struggle with chronic pain reportedly began over a decade ago with physical and emotional trauma caused by a sexual assault.

“I have always been honest about my physical and mental health struggles. Searching for years to get to the bottom of them. It is complicated and difficult to explain, and we are trying to figure it out,” Lady Gaga wrote on Instagram.

“I am looking forward to touring again soon, but I have to be with my doctors right now so I can be strong and perform for you all for the next 60 years or more. I love you so much.”

Researchers Question Value of Brain Imaging

By Pat Anson, Editor

An international team of researchers is recommending against the use of brain imaging as a diagnostic test for chronic pain, saying the tests are “inappropriate and unethical.”

"It's not possible at this point in time to say with any degree of certainty that a person does or does not have chronic pain based on brain imaging," said Karen Davis, PhD, senior scientist at the Krembil Research Institute and a professor at the University of Toronto.

"The only way to truly know if someone is in pain is if they tell you because pain is subjective and it is a complex experience. No brain scan can do that."

In recent years, technological advances in brain imaging have led to an increased use of functional magnetic resonance imaging (fMRI) to search for brain-based biomarkers for chronic pain.

Demand for brain imaging is also growing for legal purposes, including the development of a potential “lie detector” test for chronic pain.

"Use of such tools would be inappropriate and unethical," said Davis. "This technology is not foolproof. There are vast issues of variability between people and even within a person at different times. As a result, brain imaging must not be used as a lie detector for chronic pain."

Davis and her colleagues say brain-based biomarkers should only be used to supplement -- not replace -- a patient’s own reports of pain, even if testing is improved and valid protocols developed. Their recommendations were published in the journal Nature Review: Neurology.

"We are working towards biomarkers for chronic pain, but the goal is not as a lie detector test but rather to help provide personalized pain treatment options for patients," Davis. “People outside of the field of imaging might be disappointed, but the fact of the matter is the technology cannot be used to support or dispute a claim of chronic pain."

According to a 2015 study at the University of Michigan, one in eight visits to a doctor for a headache or migraine end up with the patient going for a brain scan. Often a doctor will order an fMRI to ease a patient’s fear that they may have a brain tumor or some other serious health problem. Doctors may also order a test to protect themselves in case of a lawsuit. About 1 to 3 percent of brain scans of patients with repeated headaches identify a cancerous growth or aneurysm.

University of Michigan researcher Brian Callaghan, MD, identified 74 neurological tests and procedures that are often unnecessary. Many involve the use of imaging.

“The two biggest areas that might be done more than they should are imaging for low back pain and imaging for headaches,” Callaghan said. “It’s a big problem and it costs a lot of money – we’re talking a billion dollars a year on just headache imaging.”

Other researchers believe brain imaging can be used as a valuable diagnostic tool. In a small study at the University of Colorado Boulder, researchers used fMRIs to discover a “brain signature” that identifies fibromyalgia with 93 percent accuracy. They found three neurological patterns in the brain that correlate with the pain hypersensitivity typically experienced with fibromyalgia.