Narcotic prescriptions for unrelenting visceral pain in inflammatory bowel disease (IBD) are on the rise, just as they are for pain in other non-malignant conditions. And as the prescriptions increase, so does evidence of complications and excess mortality in the IBD population.
As far back as 2006, a study by Andrea Trescot and colleagues noted that the United States held the dubious honor of consuming 80% of the world’s opioids with only 4.6% of its population.
In the context of this trend, a U.K. study recently reported that heavy use of strong opiates correlated with elevated all-cause premature mortality in IBD patients. Retrospectively analyzing the records of 3,517 Crohn’s disease (CD) and 5,349 ulcerative colitis (UC) patients in a primary care database, researchers from the University of Leeds found a significant increase in patients receiving opiate prescriptions — from 10% during the period of 1990-1993 to 30% in 2010-2013 — and a notable increase in deaths.
“Prescription of strong opiates was significantly associated with increased premature mortality of patients with CD (heavy use) or UC (moderate or heavy use),” wrote Venkat Subramanian, MD, of the Leeds Institute of Biomedical and Clinical Sciences, and colleagues. In UC patients there was a significant association between heavy use of any opiate or codeine alone and premature mortality. Tramadol alone or combined with codeine was not associated with premature mortality in patients with either CD or UC.
Previously, Laura Targownik and colleagues examined a Canadian IBD epidemiology database and reported in 2014 that within 10 years of diagnosis, 5% of opioid recipients had become heavy users, and even moderate use of opioids before IBD diagnosis was highly predictive of future heavy use. Heavy opioid use was strongly associated with mortality, carrying an odds ratio (OR) of 2.82 (95% CI 1.58-5.02). Furthermore, individuals with IBD were almost three times as likely to become heavy opioid users than were their matched controls (OR 2.91, 95% CI 2.19-3.85).
The investigators concluded that IBD is an independent risk factor for heavy opioid use and excess mortality and that clinicians should recognize risk factors for future heavy opioid use among their patients with IBD.
Despite mounting data on the adverse effects of narcotics in IBD, a 2011 study by Millie Long et al in 117 adult IBD patients admitted to a U.S. tertiary-care hospital found that 70% of patients received significant doses of narcotics during their stay. Risk factors for narcotic use in IBD patients included CD and associated variables such as disease duration and previous IBD surgery, outpatient narcotic use, smoking, psychiatric diagnoses, and concurrent irritable bowel syndrome (IBS).
“Recognizing these risk factors may allow for early interventions during the hospitalization, such as the addition of centrally acting antidepressants and avoidance of significant narcotic use, which may ultimately improve pain control and possibly avoid complications of narcotic use,” Long and co-authors wrote.
Douglas Drossman, MD, of Drossman Gastroenterology in Chapel Hill, N.C., noted that the acceptability of opioids for non-acute and non-cancer pain began in earnest back in 2001 with the Joint Commission’s Pain Standards, which aimed to address the endemic undertreatment of pain. “Before 1990 it was anathema to use opiates for IBD pain for fear of the development of toxic megacolon. They were considered inappropriate for non-malignant pain and outright dangerous in IBD,” the University of North Carolina professor emeritus and former co-director of the UNC Center for Functional GI and Motility Disorders told MedPage Today.
The Joint Commission is currently revising its standards on pain assessment and treatment in light of the current opioid epidemic.
The increased attention to pain management, combined with aggressive marketing and sophisticated delivery systems such as fentanyl patches, drew the focus away from traditional pain control methods such as antidepressants, behavioral interventions, and regional nerve blocks, Drossman explained. In the U.S., reimbursement by third-party payers also played a role. “Why spend a couple of hours in a multidisciplinary pain program when you can spend 10 minutes and write a prescription? It was a perfect storm.”
While some researchers have proposed that opiate use is just a marker for more severe disease, thereby explaining increased risks, Drossman noted that these drugs have also been associated with narcotic bowel syndrome (NBS).
“About 5% of patients on opioids end up with NBS and hyperalgesia and paradoxically have worse pain and keep going to the emergency room,” said Drossman, who recently co-authored an article on the misuse of opioids in gastroenterology. NBS needs to be identified and the patients taken off narcotic pain control.
And while agents such as nonsteroidal anti-inflammatory drugs and cyclooxygenase inhibitors can trigger flares, neuromodulators such as antidepressants, antipsychotics, and anticonvulsants, which down-regulate pain at the brain level, are increasingly being used to counteract pain-related visceral hypersensitivity. Also under investigation are molecular agents such as antagonists to nerve growth factor and transient receptor potential vanilloid receptor subtype 1 and kappa opioid receptor agonists.
These may eventually phase out the regular use of narcotics, and it won’t be too soon for Drossman: “In my opinion, after 40 years of experience and research, there is absolutely no place for opioids in managing chronic IBD pain.”