Gabapentin Won’t Cure the Opioid Crisis

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

Experimental Treatment Targets Neuropathic Pain

By Pat Anson, PNN Editor

Researchers in Denmark have developed a promising new compound to treat neuropathy that targets the hyper-sensitized nerves that cause chronic pain. The experimental compound – a peptide called Tat-P4-(C5)2 -- has only been tested in mice, but researchers hope to begin clinical trials on humans soon.

"We have developed a new way to treat chronic pain. It is a targeted treatment. That is, it does not affect the general neuronal signaling, but only affects the nerve changes that are caused by the disease," says Kenneth Lindegaard Madsen, PhD, Associate Professor at the University of Copenhagen.

"We have been working on this for more than ten years. We have taken the process all the way from understanding the biology, inventing and designing the compound to describing how it works in animals, affects their behaviour and removes the pain.”

Madsen and his colleagues recently published their findings in the journal EMBO Molecular Medicine .

The image below shows the compound Tat-P4-(C5)2 after it is injected into the spinal cord. The compound (purple) penetrates the nerve cells of the spinal cord (yellow), but not the surrounding cells (the cell nuclei are blue). The compound blocks neuropathic pain signals – the kind associated with diabetic neuropathy, shingles, phantom limb pain and chemotherapy-induced pain — from being sent to the brain.

UNIVERSITY OF COPENHAGEN

In a previous study, the researchers showed in an animal model that use of the compound can also reduce tolerance and the risk of addiction. They believe the compound will be more effective and safer than the anti‐convulsants, antidepressants and opioid medications now used to treat neuropathy.

"The compound works very efficiently, and we do not see any side effects. We can administer this peptide and obtain complete pain relief in the mouse model we have used, without the lethargic effect that characterises existing pain-relieving drugs," said Madsen.

"Now, our next step is to work towards testing the treatment on people. The goal, for us, is to develop a drug, therefore the plan is to establish a biotech company as soon as possible so we can focus on this."

Light Therapy Used to Treat Neuropathic Pain

By Pat Anson, Editor

For someone with peripheral neuropathy, even the slightest touch can cause burning, stinging or shooting pain, usually in the hands or feet.

The pain is caused when the peripheral nervous system is damaged by diabetes, shingles, chemotherapy or some other medical condition. About 8% of adults worldwide suffer from some form of neuropathy. Medications prescribed to dull the pain – such as opioids, anti-depressants or gabapentin (Neurontin) -- often prove to be ineffective, don’t last long or have unwanted side effects.

Scientists in Italy have now discovered an experimental way to treat neuropathy that provides pain relief for weeks at a time without the use of medication. In experiments on laboratory mice, researchers at the European Molecular Biology Laboratory (EMBL) in Rome identified a specific set of nerve cells in mouse skin that play a significant role in neuropathic pain.

NATURE COMMUNICATIONs

When injected with a light-sensitive chemical and then exposed to infrared light, the nerve cells pull away from the skin’s surface and stop sending pain signals. The pain-relieving effects of the light therapy appear to last for weeks.

The accompanying image shows the skin of a mouse, with the nerve cells that are responsible for sensitivity to touch highlighted in green. The neurons are primarily located around hair follicles.

The EMBL's research, first reported in the journal Nature Communications, is still in its early stages. But scientists say human skin tissue is similar to that of mice, indicating that light therapy might be effective in managing neuropathic pain in humans.

"In the end, our aim is to solve the problem of pain in both humans and animals," says Paul Heppenstall, PhD, EMBL group leader. "Of course, a lot of work needs to be done before we can do a similar study in people with neuropathic pain. That's why we're now actively looking for partners and are open for new collaborations to develop this method further, with the hope of one day using it in the clinic."

Heppenstall says light therapy works on the treated nerve cells the same way spicy food or capsaicin patches can cause nerve fibers to retract.  

"It's like eating a strong curry, which burns the nerve endings in your mouth and desensitizes them for some time," says Heppenstall. "The nice thing about our technique is that we can specifically target the small subgroup of neurons causing neuropathic pain."

There are many different types of nerve cells in skin, which respond to different sensations like vibration, cold, heat or normal pain. Researchers say those cells are not affected by the light treatment. The skin is only desensitized to a gentle touch, breeze, or tickling.

Previous attempts to develop drugs to treat neuropathic pain have mostly focused on targeting single molecules.

"We think however, that there's not one single molecule responsible, there are many," Heppenstall explains. "You might be able to succeed in blocking one or a couple, but others would take over the same function eventually. With our new illumination method, we avoid this problem altogether."

The neuropathic pain in mice was assessed with a simple touch. The mice would normally quickly withdraw their paw when it was gently touched, but after light therapy they exhibited normal reflexive response to touch. The effect of the therapy lasted for a few weeks, until the nerve endings grew back and the gentle touch caused pain again.

The 411 on Calmare Scrambler Therapy

By Michael Cooney, DC, Guest Columnist

As a chiropractor who treats various pain conditions caused by injury or disease, my biggest frustration is when our therapies do not achieve a successful patient outcome.

Often, “treatment-resistant” patients are forced to seek out more invasive procedures – surgeries, spinal cord stimulators, or powerful narcotics such as ketamine − where success has been uneven, but side effects can be significant.

I wasn’t comfortable recommending these “next level” neuropathic pain treatments for my patients. So my partner Dr. Robert Kelly and I spent two years looking for a non-invasive therapy that didn’t cause pain or come with added side effects.

Through a contact in Italy, we discovered Calmare scrambler therapy, which treats several types of drug and treatment-resistant pain, a big plus for our practice. After undergoing clinical training to use the machine and eventually testing it on patients, we saw results after just a few treatment sessions, in the majority of cases.

I’ll be honest, our aim in adding Calmare to our treatment offerings was designed to help our patients who were not responding to traditional pain therapies. No one was more surprised than I to experience the global interest in this alternative treatment option.

We have been performing Calmare Therapy since 2011, treating patients from coast-to-coast and as far away as Australia, the UK, South Africa and Brazil.

Today, we treat children, adults and seniors battling CRPS/RSD, fibromyalgia, neuropathy after chemotherapy treatment, and pain that develops after surgery or from diabetes. We have also treated many people with neuropathic pain after a shingles diagnosis.

How Scrambler Therapy “Talks” With the Brain

The brain’s reaction to pain can be compared to learning to play the piano or memorizing a poem. The more the body processes pain, the stronger the connections between pain nerves and the brain become.

When someone is injured, the brain sets up a process to heal the injury. For example, cells carry away dead tissue or it increases blood flow to the injured area. Eventually, the brain realizes the injury has healed, and cuts off the pain message.

But for some people, the brain never sends the all-important message: “There’s no more injury here. You can stop sending that pain signal.”

That’s where Calmare scrambler therapy comes in.

Using small electrodes (think EKG pads) judiciously placed in the region of the injury, the device sends a mild electric signal to the brain through the electrodes.

This message overrides the brain’s confused pain signal and corrects it to a “there’s no pain here” message.

We recommend a series of 10 daily scrambler treatments. But in many cases, the pain is lessened for the patient as soon as the first treatment.

The machine we use, the MC-5A Calmare device, has been tested in clinical trials at some of the most prestigious research institutions, including the Massey Cancer Institute at Virginia Commonwealth University, the Mayo Clinic, and the American Society of Clinical Oncology. Their studies reported significant reductions in pain associated with cancer treatment and other chronic pain conditions.

The Value of Alternative Medicine in Treating Neuropathy

The majority of patients we treat with scrambler therapy come to us frustrated and exhausted by the endless search for pain relief. They have often resorted to unproven surgeries, experimental procedures, or have used powerful pain medications that leave them mentally and physically debilitated by the drug’s side effects.

I encourage people with treatment-resistant neuropathy and their families to research and consider less invasive, alternative solutions to combat the effects of chronic pain. In some cases, the cost can be comparable to prescription medications and in-patient co-pays. The outcome can be life-changing.

Regardless of the pain therapy you choose, keep in mind there are treatments that do not involve narcotics, surgery or invasive procedures, which can result in more pain and discomfort.

Keep looking -- network with people who have your medical condition, conduct your own research, and reach out to doctors who understand the value of alternative therapy. Ask the provider to put you in touch with another patient who had the treatment. We enthusiastically offer this service through our Patient-2-Patient program.

There may very well be a solution out there to minimize your pain. But often, it’s up to you to discover it.

Michael J. Cooney has been a doctor of chiropractic for more than 30 years at Rutherford Allied Medical Group and Calmare Therapy NJ in Rutherford, New Jersey. He is one of six certified providers of Calmare in the U.S. Dr. Cooney can be emailed at calmarenj@gmail.com.

Pain News Network invites other readers to share their stories with us.  Send them to:  editor@PainNewsNetwork.org. 

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

‘Wakeup Call’ for Neurontin Abuse

By Pat Anson, Editor

A drug that is often prescribed as an alternative to opioid pain medication is increasingly being abused by patients, according to a small study that found one out of five patients taking the drug illicitly.

Gabapentin – which is sold by Pfizer under the brand name Neurontin -- is approved by the Food and Drug Administration to treat epilepsy and neuropathic pain caused by shingles.

It is also prescribed “off-label” for a variety of other conditions, including depression, migraine, fibromyalgia and bipolar disorder.

In a study of urine samples from 323 patients being treated at pain clinics and addiction treatment centers, 70 patients were found to be taking gabapentin without a prescription.

“The high rate of misuse of this medication is surprising and it is also a wakeup call for prescribers. Doctors don’t usually screen for gabapentin abuse when making sure patients are taking medications, such as opioids, as prescribed. These findings reveal that there is a growing risk of abuse and a need for more robust testing,” said Poluru Reddy, PhD, medical director of ARIA Diagnostics in Indianapolis, IN. Reddy presented his study at the annual meeting of the American Association for Clinical Chemistry in Philadelphia.

Researchers found that of those patients taking gabapentin illicitly, over half (56%) were taking it with an opioid, about a quarter (27%) with an opioid and muscle relaxant or anxiety medication, and the rest with other substances. The urine samples came primarily from pain clinics in Indiana, Arizona, and Massachusetts.

“Little information exists regarding the significance of Gabapentin abuse among clinical patients. Until recently, it was considered to have little potential for abuse however this review has shown that a significant amount of patients are taking Gabapentin without physician consent. This could be due to the fact that recent studies have revealed that Gabapentin may potentiate the ‘high’ obtained from other central nervous system acting drugs,” wrote Reddy.

"Patient safety is Pfizer’s utmost priority.  We strongly support and recommend the need for appropriate prescribing and use of all our medicines," a spokesperson for Pfizer said in an email to Pain News Network.

Gabapentin is not scheduled as a controlled substance and when taken alone there is little potential for abuse. But when taken with other drugs, such as opioids, muscle relaxants, and anxiety medications like Valium and Xanax, researchers say gabapentin can have a euphoric effect.

Between 2008 and 2011 the number of emergency room visits for misuse or abuse of gabapentin increased by nearly five times, according to the Drug Abuse Warning Network. Side effects from gabapentin include weight gain, dizziness, ataxia, somnolence, nervousness and fatigue.

Increased Prescribing of Gabapentin

A report by IMS Health found that 57 million prescriptions for gabapentin were written in the U.S. in 2015, a 42% increase since 2011.

Gabapentin is one of several medications being promoted by the Centers for Disease Control and Prevention as a "safer"  alternative to opioids.  The American Pain Society recently recommended that gabapentin be considered for post-operative pain relief.

But the growth in gabapentin prescribing is drawing scrutiny in the UK, where the Advisory Council on the Misuse of Drugs (ACMD) recommended earlier this year that gabapentin and pregabalin (Lyrica) be reclassified as Class C controlled substances, which would make them harder to obtain.

“Both pregabalin and gabapentin are increasingly being reported as possessing a potential for misuse. When used in combination with other depressants, they can cause drowsiness, sedation, respiratory failure and death,” said Professor Les Iverson, ACMD chairman, in a letter to Home Office ministers.

“Pregabalin causes a ‘high’ or elevated mood in users; the side effects may include chest pain, wheezing, vision changes and less commonly, hallucinations. Gabapentin can produce feelings of relaxation, calmness and euphoria. Some users have reported that the ‘high’ from snorted gabapentin can be similar to taking a stimulant.”

Gabapentin is "one of the most abused and diverted drugs” in the U.S. prison system, according to Jeffrey Keller, MD,  the chief medical officer of Centurian, a private company that provides prison healthcare services.

“Inmates show up at my jails all the time with gabapentin on their current medication list,” Keller wrote in Corrections.com. “It produces euphoria, a marijuana-like high, sedation, and, at high enough doses, dissociative/psychedelic effects. It works so well that it is used in the drug community to mellow out methamphetamine tweaking and to cut heroin. Since drug abusers know about these illicit uses of gabapentin on the streets, once they get to jail they often view gabapentin as an obtainable ‘jail substitute’ for their preferred drugs.

“Unfortunately, the abuse potential of gabapentin is not recognized much outside of jails and prisons. Community prescribers are generally unaware that gabapentin can be misused and (in my experience) are often incredulous and even disbelieving when told about ‘the dark side’ of gabapentin.”

Gabapentin (Neurontin) has a checkered history. Originally developed as a nerve drug, Pfizer agreed to pay $430 million in fines to resolve criminal and civil charges for illegally marketing Neurontin to treat conditions it was not approved for. According to some estimates, over 90% of Neurontin sales are for off-label uses.

In 1999, a Pfizer executive was so mystified by Neurontin’s popularity he called it the “snake oil of the twentieth century.”