Are You Paying Too Much for Pregabalin?

By Pat Anson, PNN Editor

It didn’t take long for cheaper generic versions of pregabalin to take a bite out of Pfizer’s monopoly of Lyrica, a drug widely used to treat fibromyalgia, diabetic neuropathy and other types of chronic pain.

Last month the U.S. Food and Drug Administration gave approval to rival drug makers to begin selling generic pregabalin after Pfizer’s patent on Lyrica expired. According to FiercePharma, Pfizer lost about a third of the market for pregabalin to 16 competitors by the end of July.  

It’s not hard to see why. According to Healthcare Bluebook, a 60-day supply of 75mg Lyrica sells for a “fair price” of $472. That compares to generic versions that sell for about $28.

“The price that most patients pay is set by insurers. The cost difference for patients between brand-name Lyrica and generic pregabalin may vary depending on the patients’ insurance plan, the state in which their prescription is filled, or the pharmacy where they pick up their prescription,” said Steven Danehy, a Pfizer spokesman.

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As of August 9, Lyrica still had about 43% of the market for pregabalin, but that’s likely to change as patients, doctors and insurers became more aware of the significant difference in price.

Pregabalin is approved by the FDA for the treatment of pain associated with shingles, spinal cord injury, fibromyalgia, and diabetic peripheral neuropathy. It is also commonly prescribed "off label" for other types of chronic pain.

Pregabalin is a Schedule V controlled substance, which means it has a low potential for abuse. In recent years, however, there is growing concern that pregabalin and its sister drug gabapentin (Neurontin) are being abused and overprescribed.

The drugs, which belong to a class of nerve medication called gabapentinoids, were originally developed to treat epilepsy, not pain. Prescriptions for gabapentinoids have tripled over the past 15 years as more doctors prescribed them as “safer” alternatives to opioids.

Deaths involving gabapentinoids have increased in the UK, Australia and Canada, where some addicts have learned the drugs can heighten the euphoric effect of heroin and other opioids. The drugs were recently classified as controlled substances in the UK.

Gabapentinoids Raise Risk of Suicide and Overdose in Younger People

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Doctors Say Guidelines Exaggerate Effectiveness of Lyrica and Neurontin

By Pat Anson, PNN Editor

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

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

“Gabapentinoids have become frequent first-line alternatives in patients with chronic pain from whom opioids are being withheld or withdrawn, as well as in patients with acute pain who traditionally received short courses of low-dose opioid,” wrote Christopher Goodman, MD, and Allan Brett, MD, of the University of South Carolina School of Medicine.

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

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

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

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

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

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

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

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

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

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

Risky Combination: Opioids and Gabapentin

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

Can Gabapentin Improve Your Sex Life?

By Pat Anson, PNN Editor

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

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

Add sexual function to the list.

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

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

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

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

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

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

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

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

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

Patients at Ohio Hospital Have Surgery Without Opioids

By Pat Anson, PNN Editor

Would you want to go through a major surgery without the use of opioid pain medication?

Patients at an Ohio hospital are getting acetaminophen, gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs) to manage their pain before and after colorectal operations – and their surgeons say the treatment results in better patient outcomes.

“Over 75 percent of our elective colorectal patients underwent surgery without requiring narcotic analgesics postoperatively, including after discharge,” says Sophia Horattas, MD, of Cleveland Clinic Akron General Hospital.  “During this time period our patient satisfaction scores improved as well as patients' perceptions of pain control.”

All eight general surgeons at Akron General adopted the non-opioid treatment protocol in 2016, applying it to patients who had elective colon operations. Prior to surgery, the patients were all educated about pain management, non-opioid analgesics, and the risks associated with opioids.

Researchers evaluated 155 of the patients and presented their findings this week at the American College of Surgeons Clinical Congress in Boston.

Overall, 83 percent (128) of the patients did not need opioid medication after their operations. Among those who did, use of opioids before surgery was often an indicator that they would want them again. Nine of the 15 patients who had prior experience with opioids used them again after surgery.

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Among the remaining 140 patients who did not use opioids before surgery, 85 percent (119) did not need opioid medication for pain relief.

The researchers found that patients who used opioid painkillers typically spent more time in the hospital; an average of 2.7 days vs. 2.3 days for the non-narcotic group.

“Patient education played a large role in protocol compliance, and patient satisfaction improved as they were able to avoid prolonged fasting, achieve improved pain control without the side effects of narcotic analgesia, and be discharged home earlier,” said Horrattas.

For pre-emptive analgesia before surgery, patients received one dose of acetaminophen, gabapentin, and the NSAID celecoxib (Celebrex).  In the operating room, patients received a nerve block and underwent anesthesia with the non-opioid pain relievers ketamine and lidocaine.   

Surgeons at Akron General have since adopted the non-opioid protocol for other major abdominal operations, such as bariatric procedures, gynecological and genital/urinary tract procedures, and liver and gall bladder operations.

“One of the great things about our protocol is its reproducibility.  Once we developed our program, we found that it could be standardized across departments with consistently reproducible results,” said Horattas.

Akron General’s protocol is similar to guidelines adopted by the American Pain Society (APS) for postoperative pain care. The APS also encourages the use of non-opioid medications such as acetaminophen, NSAIDs, gabapentin (Neurotin) and pregabalin (Lyrica).  

Akron General gets below average ratings for patient satisifaction from Hospital Compare, a Medicare survey that asks patients about their experiences during a recent hospital stay. The hospital received only two of a possible five stars, which places it in the bottom third of hospitals nationwide. Only 68% of Akron General’s patients said they would definitely recommend the hospital.

According to Healthgrades, 3 percent of the patients died after a colorectal surgery at Akron General, which is slightly below the national average for that procedure.

Opioid Addiction Rare After Surgery

In recent years, many hospitals have shifted away from routinely giving patients opioids during and after major surgeries -- even though it is rare for patients to become chronic opioid users.

A large Canadian study found that only 0.4% of elderly patients that were prescribed opioids while recovering from a heart, lung, colon, prostate or hysterectomy operation were still using them a year after their surgeries.

Another large study published this year in the British Medical Journal found similar results. Only 0.2% of patients who were prescribed opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Long-term opioid use after dental surgeries is also rare. A recent study published in JAMA found that only 1.3% of teens and young adults who were given opioids after wisdom teeth removal were still being prescribed opioids months after their initial prescription.

The vast majority of patients still prefer opioids and perceive them as the most effective form of pain relief after surgery. In a recent survey of over 500 adults who were scheduled to have surgery, researchers at Thomas Jefferson University Hospital in Philadelphia found that 77% expected opioids, 37% expected acetaminophen, and 18% expected a NSAID for pain relief.

"Patients often assume they will receive opioids for pain, believing they are superior, and therefore may pressure physicians to prescribe them after surgery," said lead author Nirmal Shah, DO, an anesthesia resident at Thomas Jefferson University Hospital.

"But research shows opioids often aren't necessarily more effective. Clearly, we need to provide more education to bridge that gap and help patients understand that there are many options for pain relief after surgery, including other pain medications such as acetaminophen and ibuprofen."

Lyrica Not Effective for Treating Traumatic Nerve Pain

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

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

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