Fibromyalgia Medication Tied to Suicidal Behavior, Overdoses

Gabapentinoids, a group of drugs used to treat conditions including fibromyalgia, may be associated with an increased risk of suicidal behavior, unintentional overdoses, head/body injuries, and road traffic incidents/offenses, according to new research.

The two main gabapentinoids are gabapentin and pregabalin (including the popular drug Lyrica). In Europe, they are used to treat epilepsy and neuropathic pain disorders, and pregabalin is used to treat generalized anxiety disorder in Europe and fibromyalgia in the United States. The drugs have become increasingly more popular and are currently one of the world’s top 15 drugs for revenue.

“Concerns have, however, been expressed about overprescription, particularly for pain relief, as well as adverse effects, including dizziness, somnolence, balance problems, blurred vision, coordination problems, and impairments in cognitive performance,” according to the study authors, whose work was published in The BMJ. “Although a 2008 Food and Drug Administration study of antiepileptic drugs reported an increased suicidal risk, separate analyses for pregabalin and gabapentin did not show clear effects.”

The study included patients from the Swedish Prescribed Drug Register who filled at least two consecutive prescriptions for pregabalin or gabapentin between 2006 and 2013. The primary analysis did not include patients who collected prescription, the authors noted, “owing to uncertainty over drug adherence or tolerance.” The primary outcomes were:

• Suicidal behavior (emergency hospital visits due to self-inflicted injury or death by suicide)
• Unintentional overdoses (emergency hospital visits or death due to poisoning attributed to illicit drugs, medications, and biological substances; accidental noxious poisoning; and acute intoxications/overdoses by alcohol/illicit drugs)
• Head/body injuries (emergency hospital visits or death due to superficial, open, or crushing injuries, dislocations, fractures, and amputations [excluding intentional self-injuries])
• Road traffic incidents/offenses (emergency hospital visits or death due to road traffic incidents, or arrests for/convictions of traffic offenses [reckless driving, hit-and-runs, causing death or injury by driving, moving violations])
• Violent crime arrests (crimes against people [attempted, completed, and aggravated forms of murder, manslaughter, unlawful threats, harassment, robbery, arson assault, assault on an official, kidnapping, stalking, coercion, and all sexual offenses)

Gabapentinoids Associated with Adverse Outcomes, Differences between Gabapentin and Pregabalin

A total of 191,973 patients were included in the review, of whom 10,026 (5.2%) received treatment for suicidal behavior or died due to suicide. In total, 70,522 patients (36.7%) sustained head/body injuries, 17,144 (8.9%) had an unintentional overdose, 12,070 (6.3%) had a road traffic incident/offense, and 7,984 (4.1%) committed a violent crime and were arrested. In within-individual analyses, gabapentinoid users had higher risks of of suicidal behavior and suicide deaths (age adjusted hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.20 to 1.32), unintentional overdoses (HR 1.24, 95% CI 1.19 to 1.28), head/body injuries (HR 1.22, 95% CI 1.19 to 1.25), and road traffic incidents and offenses (HR 1.13, 95% CI 1.06 to 1.20), but the association was not as strong for violent crime arrests (HR 1.04, 95% CI 0.98 to 1.11). Researchers also assessed pregabalin and gabapentin separately and fund an increased risk for all outcomes with pregabalin use. Risks associated with gabapentin use were either decreased or not statistically significant. Patients aged between 15 and 24 years had increased risks for all outcomes.

Pfizer, manufacturer of Lyrica, said in an emailed statement to Reuters, “When prescribed and administered appropriately as per the approved label, Lyrica (pregabalin) is an important and effective treatment option for many people. The clinical effectiveness of this medicine has been demonstrated in a large number of robust clinical trials among thousands of patients.”

Study author Seena Fazel BSc (Hons), MBChB, MD, FRCPsych, an honorary consultant forensic psychiatrist and professor of forensic psychiatry at the University of Oxford, told Reuters in an interview, “These medications clearly have a role if they’re used in people who have clear indications for their use.” However, Dr. Fazel added, “We need to be more careful about how these medications are prescribed and I think at the very least we should review guidelines about their use just to make sure these guidelines are up to date with the latest evidence.”

The study authors wrote in their conclusion, “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.”

Sources: The BMJ, Reuters