New Concerns About Gabapentin and Pregabalin (Lyrica) for Nerve Pain

Several years ago, a review of the FDA’s Adverse Event Reporting System (FAERS) revealed some disconcerting data about commonly prescribed drugs for nerve pain (ISMP QuarterWatch Reports (March 27, 2019). This independent publication provided insights on emerging drug risks based on information submitted to the Food and Drug Administration. Doctors primarily prescribe GABA agonists (aka gabapentinoids) like gabapentin (Neurontin) and pregabalin (Lyrica) for neuropathic (nerve) pain. They may also prescribe Lyrica to treat fibromyalgia. Perhaps unexpectedly, the ISMP report raised safety concerns about gabapentin and pregabalin that deserve some careful consideration by physicians, patients and FDA safety officers.

An Additional Gabapentin Scandal?

A further careful analysis in the Journal of Clinical Epidemiology (Oct. 21, 2023) reveals that important adverse reactions detected in six clinical trials of gabapentin were not included in the early published reports.

The authors introduce their research this way:

“In 1993, gabapentin (Neurontin) was approved to treat epilepsy by the U.S. Food and Drug Administration (FDA). To increase sales, gabapentin’s manufacturer encouraged ‘off label’ prescribing by publishing favorable clinical trial results in medical journals. Those articles over-estimated gabapentin’s benefits and underestimated its harms. Pfizer pleaded guilty to criminal and civil charges for illegal marketing, and it settled claims of defrauding patients and benefit providers.

“Today, gabapentin continues to be prescribed widely for multiple conditions. Prescribing might be influenced by systematic reviews and guidance based on incomplete evidence.”

These researchers analyzed data from six randomized clinical trials of gabapentin. After all, RCTs are supposed to be the “gold standard” for drug studies. The authors of this new overview point out that the results and summaries failed to include many side effects. This had an impact on subsequent reviews of gabapentin.

The investigation revealed that:

“Many of the harms observed in these trials have not been included in systematic reviews that are based on published reports…”

The bottom line seems to be that physicians and patients may not be aware of some of the important early concerns about gabapentin and pregabalin.

Gabapentin and Pregabalin and the Brain:

No doubt you have heard of the neurotransmitter called serotonin. One of the most widely prescribed antidepressants, fluoxetine (Prozac), became a household name because it was a selective serotonin re-uptake inhibitor (SSRI).

You have probably read about dopamine. It has been described as the “feel-good” neurotransmitter. Think of it as the reward neurochemical. If you experience something wonderful, the pleasurable feelings are probably impacted by dopamine.

Have you ever heard of a neurotransmitter called GABA (gamma-aminobutyric acid)? We didn’t think so. Whereas most neurotransmitters stimulate neurons, GABA is more like a brake on the brain. Neuroscientists refer to this as an inhibitory action. Not surprisingly, drugs that “calm” the brain often attach themselves to GABA receptors and/or enhance the activity of GABA. Think booze, barbiturates, benzodiazepines such as diazepam (Valium) or even sleeping pills like zolpidem (Ambien).

Gabapentin and pregabalin (Lyrica) are considered GABA analogs or gabapentinoids. In addition to being prescribed for nerve pain, they sometimes are used to treat “partial onset seizures.” You get the picture: brain brakes for epilepsy or sensations of pain.

Why Are GABA Drug Prescriptions Skyrocketing?

Prescriptions for these powerful brain modulating meds are way up.

An article in JAMA Internal Medicine (Feb. 2018) notes that:

“The use of gabapentinoids more than tripled between 2002 and 2015.”

According to our calculations, over 12 million Americans are now taking either gabapentin or pregabalin. That represents nearly 60 million prescriptions annually!

We suspect that many physicians have become worried about prescribing opioids to patients suffering from chronic pain. They have either reduced the dose of opioids and added a drug like gabapentin or substituted a GABA analog entirely for the more powerful pain relievers. That’s not just our opinion.

An article published in the New England Journal of Medicine (Aug. 3, 2017) stated:

“We believe, however, that gabapentinoids are being prescribed excessively — partly in response to the opioid epidemic…Patients who are in pain deserve empathy, understanding, time, and attention. We believe some of them may benefit from a therapeutic trial of gabapentin or pregabalin for off-label indications, and we support robust efforts to limit opioid prescribing. Nevertheless, clinicians shouldn’t assume that gabapentinoids are an effective approach for most pain syndromes or a routinely appropriate substitute for opioids.”

The report from the March 27, 2019 ISMP QuarterWatch reveals:

“Gabapentin is so widely used that it is reported taken by more adults than any other psychoactive drug except the opioid combination acetaminophen/hydrocodone (Vicodin). It is so widely abused that a study of overdose deaths showed 32% had included it in a cocktail of lethal drugs that mostly included potent opioids.”

You can read more about the rise in gabapentin and pregabalin prescriptions at this link.

Are Doctors Overprescribing Gabapentin and Pregabalin (Lyrica) for Pain?

A Reader Wonders Whether Gabapentin is Worth the Risk:

Q. My doctor prescribed gabapentin to treat nerve pain. I’m not sure about taking it because I have read it increases the risk for dementia. Also, it may leave residual effects after stopping. I am not epileptic. Should I be concerned?

A. When older people start taking the anticonvulsant gabapentin, they are more likely to fall (Frontiers in Pharmacology, Nov. 25, 2022).  That alone is worrisome. Furthermore, evidence shows that people taking gabapentin are significantly more likely to develop dementia than those not using it (Frontiers in Pharmacology, May 30, 2023). If you have other options to treat your nerve pain, you might want to explore them further.

A Reader Challenges This Research!

We recently received this message from a reader of our nationally syndicated newspaper column:

Q. Doctors are increasingly prescribing gabapentin to treat nerve pain. My wife recently showed me a column you had written on a link between gabapentin and dementia. She has taken this drug for neuropathy resulting from chemotherapy for breast cancer, so she was understandably alarmed.

As a retired professor, I searched the medical literature. After I found the article you cited from Frontiers of Pharmacology, I located another one with better methodology (Journal of Affective Disorders, Aug. 1, 2024).

The researchers found no significant difference in the risk of dementia between people who had taken a lot of gabapentin and those who’d had only a little. Isn’t that a better way to determine if this is a real problem?

A. Your sleuthing has revealed a classic challenge in interpreting research. The original study we cited (Frontiers in Pharmacology, May 30, 2023) analyzed data from more than 200,000 patients in Taiwan.

The authors concluded:

“Patients treated with gabapentin or pregabalin had an increased risk of dementia.”

The evaluation you found covered the same patient population but reached a completely different conclusion. As you noted, the authors determined:

“Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender.”

It’s hardly surprising that people experience whiplash when research is contradictory. That is the nature of science, however. It can take time to discover what is really going on.

Why Are There Dependency Concerns About Gabapentin and Pregabalin?

An analysis from the ISMP QuarterWatch reveals some disconcerting data:

• “Risky polypharmacy. Nearly one-half of GABA analog patients were also taking 10 or more other drugs, increasing the risk of interactions, overdose, or inhibiting effects on other needed drugs.

• “CNS depression and overdose. 35% were also sustained users of opioids; another 18% were regularly taking an additional drug that activated GABA receptors such as alprazolam (Xanax) and zolpidem (Ambien).

• “Untested psychiatric combinations. 44% of GABA analog drug patients were also in sustained use of various antidepressant drugs. This suggests that doctors observing poor responses to antidepressant drugs were adding GABA analog drugs in untested and unapproved combination therapy.”

Are There Concerns About Gabapentin and Pregabalin Dependence?

The QuarterWatch also notes that:

• “Withdrawal symptoms/dependence. More than 1,200 reports described withdrawal syndromes, drug abuse, intentional misuse, or overdose.

• Mental impairment. Patients complained of memory loss, memory impairment, confusion, dizziness, and falls.”

We suspect that many health professionals are unaware of concerns about gabapentin and pregabalin dependence. In many cases, they assume that patients could discontinue such drugs at any time without problems. That is not what we are hearing from visitors to this website.

Ivy was not told she would need to wean herself off gabapentin slowly:

“I have taken 3600mg/day of Neurontin (gabapentin) for about 15 years for small and large fiber neuropathy and other neuropathic pain all caused by Lyme disease. I never had any side effects…in fact, I tell people gabapentin has no side effects!

“The only problem I had was when a doctor told me to stop taking it and to take GABA supplements instead because they are the same thing. They are not. I had withdrawal symptoms that made me feel like I was going insane. I cried all the time, etc. I’m surprised I didn’t have seizures. I didn’t realize why it was happening but went back on the gabapentin…and they went away.”

Jay wasn’t warned about a discontinuation syndrome:

“I was prescribed gabapentin after lower back surgery. Not sure it helped with the nerve pain. I developed a canker sore on my lip after a couple weeks. I also experienced night sweats (and unusual body odor).

“The doctor didn’t say anything about side effects upon stopping gabapentin suddenly. I found out what they were when I ran out and didn’t refill–anxiety, insomnia, feeling ‘crazy.’ It’s been 5 days and I finally got a decent night’s sleep. Even with the withdrawal symptoms I’m not going back on gabapentin!”

Judy had problems with Lyrica (pregabalin):

“I am currently tapering Lyrica from 225 mg daily to 200 mg. It has been almost a month. I have been on Lyrica for 15 months. I suffer from severe chest and spinal pain due to a rare condition. The nerve pain has returned with a vengeance, but I am determined to taper to 150 mg daily. The brain fog, lack of concentration, drowsiness, etc. was ruining my life. Withdrawal has been a nightmare.”

Side Effects of GABA Analogs:

Gabapentin can cause symptoms of depression, drowsiness, dizziness, fatigue, brain fog, balance problems and visual difficulties. Patients should be warned about the possibility of suicidal thoughts. If such occur, people should contact the prescriber immediately.

Pregabalin can also lead to cognitive difficulties, unsteadiness and dizziness. Some people develop coordination problems, fatigue, confusion, blurred vision, fluid buildup (edema) and dry mouth. If depression or suicidal thoughts occur, the prescribing physician should be notified immediately!

You can learn more about the side effects of GABA analogs at this link. There are over 800 comments so you can read about the experiences of many other patients.

Surprising Gabapentin Side Effects

Some People Get Relief from Nerve Pain:

We do not want to paint a grim picture about gabapentinoids. We hear from many people that concerns about gabapentin and pregabalin are overblown and that such drugs do help relieve nerve pain. Here are just a few examples:

Gin in Granby, Connecticut, reports positive results:

“Tingling and numbness are relieved with gabapentin. I am not depressed taking it. Rather I am thrilled to not have to experience neuropathy. I don’t have any side effects to speak of. If I do, they are minimal.”

Janet in Virginia is also a fan of gabapentin:

“It took two years to finally get a diagnosis of peripheral neuropathy in my feet that has come up my legs. I’ve been on Neurontin (now gabapentin) for over 25 years. That medicine has helped me live!

“Early mornings are bad until 8:30 when the pills kick in. I was also put on tramadol. These meds have allowed me to get around, even drive some. Yes, I am sleepy and off balance but these side effects are worth it.”

Lyn reports that gabapentin helps her:

“I have very debilitating polyneuropathy. I have been on gabapentin for about 8 years. It does help with the pain in my feet. I have bad loss of balance, fuzzy head and have fallen twice. People with neuropathy will take and do anything to relieve the jabbing, burning pains. Gabapentin is the only help I have found. I have tried everything, except Marijuana.”

Final Concerns About Gabapentin and Pregabalin:

We suspect that there is a lot of off-label prescribing of gabapentin. That may stem in part from the aggressive marketing of Neurontin for which the company was fined a huge amount of money. You can learn about this sad saga in the history of gabapentin at this link:

Gabapentin for Pain Drove Patient to Brink of Suicide

We agree with the conclusions of Quarter Watch:

“Substantial action is needed to reduce inappropriate use of GABA analog drugs… Further, treatment guidelines are needed to discourage incidental off-label use without careful monitoring and patient assessment. Other risks—notably possible harmful effects of long-term use—have not been adequately assessed in drugs almost exclusively tested in short-term trials. With the exception of opioid misuse, it would be hard to find a drug safety issue today affecting so many million adults where neither risks nor benefits have been adequately established.”

Reader Response, Please:

Share your own experience or concerns about gabapentin or pregabalin in the comment section below.