Friday, December 16, 2011

Opioids for Chronic Abdominal Pain?

Abdominal Pain Chronic noncancer-related abdominal pain is a frequent reason for outpatient healthcare visits and can be difficult to treat. A recently reported study found that during a 12-year period, through 2008, there was an increasing trend of opioid analgesic prescribing for this ailment. Although opioids have not been adequately assessed for this purpose and may complicate or worsen abdominal pain, the validity of this present research and needs for further clarification should be considered before reaching any conclusions.

Writing in the December 2001 edition of Clinical Gastroenterology and Hepatology, a research team led by Spencer D. Dorn, MD, MPH, of the University of North Carolina School of Medicine, reports an investigation seeking to estimate trends and factors associated with opioid prescribing for chronic noncancer-related abdominal pain in the United States [Dorn et al. 2011]. Visits by adults to U.S. outpatient clinics for abdominal pain were identified from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) covering 1997 through 2008. Data were weighted to produce nationwide estimates of opioid prescriptions over time.

Opioid Probability The researchers divided the total 12-year time span into four 3-year increments for analysis. The primary outcome measure was the probability of receiving an opioid during a visit, expressed also as the proportion of visits for chronic abdominal pain in which an opioid analgesic was prescribed for the disorder. On this measure there was more than a 2-fold increase, from an opioid being prescribed during 5.9% of visits in 1997-1998 to 12.2% of visits in 2006-2008. The Figure at left illustrates this statistically significant trend (P=0.03), with 95% Confidence Intervals (vertical error bars) for each time period.

Conversely, during this same time period the total number of outpatient visits for chronic abdominal pain consistently decreased, from an estimated 14.8 million visits during 1997-1999 to 12.2 million visits during 2006-2008 (P-value for trend = 0.04). Opioid prescriptions were most common among patients aged 25-to-40 years old, and least common among uninsured and/or African American patients. Gender, geographic region, urban location, and survey setting were not associated with opioid prescribing patterns.

The researchers conclude that the strongest predictor of opioid prescription for chronic noncancer abdominal pain was the year of visit (2006-2008), and they intimate in their discussion that this trend may represent an inappropriate application of opioid analgesics. However, specific reasons for the trend and its consequences were unclear, so further studies are needed for a better understanding.

COMMENTARY: According to the researchers, the rise in opioid prescriptions for chronic abdominal pain raises several concerns: First, using opioids to treat chronic noncancer pain of any type is supported by only limited evidence. Second, opioids are frequently misused and sometimes abused. However, they do note that their investigation did not find any increases in substance-use disorder diagnoses associated with increased opioid prescribing in patients with abdominal pain.

Third, they state, when used over long periods of time, opioids may trigger other gastrointestinal symptoms, most commonly constipation, but also lower abdominal pain, nausea, and vomiting. A smaller subset of individuals may develop what the researchers called “narcotic bowel syndrome,” characterized by chronic or frequently recurring abdominal pain that worsens despite continued or escalating opioid dosage. However, their research did not record any opioid-related problems.

Despite the concerns about this application of opioid analgesics, the finding that opioids were least likely to be prescribed for uninsured and African American patients is troubling. This seems to be one more confirmation that race and socioeconomic status play negative roles in the treatment of pain in America and may represent an unacceptable systematic bias in healthcare delivery.

There also are a number of important limitations of this investigation that should be considered by critical readers:

  • To begin, the reported increasing trend in opioid prescribing during the 12-year time span might not be clinically significant. The greatest increases came during 2006-2008 and, while the researchers do not provide data necessary for calculating a standardized effect size for differences between 1997-1999 and 2006-2008, the overlapping 95% CI error bars for those time periods (see Figure above) suggest the possibility that there could be only a relatively small and clinically unimportant difference (even though the trend was statistically significant).

    Furthermore, the researchers found that their results were skewed by including tramadol among the prescribed opioids. Tramadol is somewhat unique in that it exhibits weak agonist actions at the mu-opioid receptor and, at the same time, releases serotonin and inhibits the reuptake of norepinephrine. When they performed an analysis excluding tramadol, the trend for increases in opioid prescriptions was no longer statistically significant.

  • The NAMCS and NHAMCS from which data were derived do not include information regarding drug dosage and duration of use. So, it is possible that, besides a high reliance on the unique properties of tramadol, prescribers might have been giving patients only low doses of any opioids for brief periods of time. Therefore, the approach to opioid therapy prescribing for abdominal pain, even if actually increasing through the years, might have been appropriately conservative and cautious; however, this is completely unknown from available data.

  • Additionally, the researchers concede that recording of the reason-for-visit codes (including acute vs chronic condition) in the surveys could be inaccurate, and the primary and secondary diagnoses also are muddled in the report. The authors include a pie graph illustrating the relative percentage of 7 diagnostic categories for which treatment was sought, including: abdominal pain in general; upper, lower, or miscellaneous GI disorder; irritable bowel syndrome; any non-GI disorder; and no or missing diagnosis. However, there are 7 slightly different solid shades of gray in the graph legend to represent these and each is not sufficiently distinctive from the others to accurately identify the respective category.

    While these 7 categories were somewhat vague in the first place, there is no way of gauging from the pie chart the most prominent diagnoses for which opioids might have been prescribed. The data were not otherwise presented in the text, so this elaborate graphic presentation was nothing more than a confusing and unhelpful waste of space.

This study raises worthwhile questions about whether there is a role for opioid therapy in the management of chronic noncancer-related abdominal pain. However, the validity of increasing trends in recent years regarding this practice should be cautiously considered and it is important that the types of abdominal pain being treated and the opioid regimens prescribed are much better defined before reaching any conclusions.

REFERENCE: Dorn SD, Meek PD, Shah ND. Increasing Frequency of Opioid Prescriptions for Chronic Abdominal Pain in US Outpatient Clinics. Clin. Gastroenterol. Hepatology. 2011(Dec);9(12):1078-1085 [abstract here].