ORIGINAL ARTICLE
Narcotic Use and Misuse in Crohn’s Disease Justin A. Crocker, MD,* Huimin Yu, MD, PhD,* Mark Conaway, PhD,† Anne G. Tuskey, MD,* and Brian W. Behm, MD*
Background: The rate of narcotic misuse in the inflammatory bowel disease population is not well studied. The primary aim of this study was to determine in Crohn’s disease (CD) whether a concurrent functional gastrointestinal disorder (FGID) was associated with increased rates of chronic narcotic use. Second, we aimed to identify potential risk factors for narcotic misuse.
Methods: A retrospective chart review of patients with CD followed at the University of Virginia’s Gastroenterology Clinic from 2006 to 2011 was performed. The prescription monitoring program was accessed to confirm narcotic prescription filling histories. Narcotic misuse was defined as narcotic prescriptions filled from 4 or more prescribers and at 4 or more different pharmacies.
Results: Nine hundred thirty-one patients with CD were included in the study cohort. Eighty-seven (9.3%) patients were identified as having a concurrent FGID, and 192 (20%) were taking chronic narcotics. Patients with FGID were more likely to be taking chronic narcotics (44% versus 18%, P , 0.001). Thirty-seven percent (32/87) of patients with an FGID were misusing narcotics, compared with 9.6% (81/844) (P , 0.0001). Multivariate logistic regression demonstrated a significant association of misuse in patients with a concurrent FGID (odds ratio ¼ 3.33, 95% confidence interval, 1.87–5.93).
Conclusions: Twenty percent of patients with CD were using chronic narcotics with higher rates in those with FGID. Using the prescription monitoring program, a significant proportion of patients with CD with an FGID were misusing narcotics. We would recommend screening for narcotic misuse in patients with CD with a concomitant FGID and consider using prescription monitoring programs to identify others at risk for misuse. (Inflamm Bowel Dis 2014;20:2234–2238) Key Words: Crohn’s disease, functional GI disorders, prescription narcotics
C
rohn’s disease (CD) is a chronic inflammatory disorder characterized by recurring episodes of inflammation in the gastrointestinal tract. Nearly all patients with CD experience abdominal pain during the course of their disease and in some cases are given narcotic medications for symptom management.1,2 Chronic prescription narcotic use has not been shown to be effective in the management of CD and has been associated with increased risk of disease complications, including serious infection and mortality.3,4 Despite these negative effects, patients with CD have been found to have fairly high rates of chronic prescription narcotic use.5,6 CD is also associated with increased rates of functional gastrointestinal disorders (FGID) that can lead to abdominal symptoms in the absence of active intestinal inflammation. The prevalence of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease (IBD) has been shown to be 2 to 3 times higher than that in the general population.7 Some Received for publication June 11, 2014; Accepted July 13, 2014. From the *Division of Gastroenterology, Department of Medicine, University of Virginia, Charlottesville, Virginia; and †Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia. The authors have no conflicts of interest to disclose. Reprints: Brian W. Behm, MD, PO Box 800708, Charlottesville, VA 22908 (e-mail: [email protected]). Copyright © 2014 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000194 Published online 9 September 2014.
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studies report over 80% of patients with inactive IBD meet criteria for at least 1 FGID.8 Prescription narcotics generally are poor treatment options for managing pain related to FGID because of the negative narcotic-related effects of intestinal dysmotility and associated visceral hyperalgesia.9 The use of prescription narcotic medications for chronic nonmalignant pain has increased significantly over the past decade in the United States, and over this time, misuse of prescription narcotics has reached epidemic levels.10 Many states have established prescription monitoring programs (PMPs) for narcotic medications, which are online databases that provide a record of each prescription narcotic filled, the quantity dispensed, the prescribing provider, and the filling pharmacy. With these databases, there is less fragmented documentation of narcotic filling patterns in the outpatient setting,11,12 and PMPs have been found to reduce rates of inappropriate narcotic prescribing and misuse.11–13 Behaviors that would suggest prescription narcotic misuse include patients receiving narcotic prescriptions from multiple prescribers, using multiple pharmacies, using multiple narcotic types, and early prescription refills. Although there is not a consensus definition of prescription narcotic misuse, Katz et al13 defined misuse using the criteria of 4 or more prescribers and 4 or more pharmacies in a 12-month period (4 + 4) as concerning for misuse or “doctor shopping.” Prescription narcotic misuse has not been evaluated specifically in the CD patient population to our knowledge. In addition, the prevalence of prescription narcotic use and misuse in Inflamm Bowel Dis Volume 20, Number 12, December 2014
Inflamm Bowel Dis Volume 20, Number 12, December 2014
patients with CD and concomitant FGIDs has not been well studied. The aim of this study was to determine whether patients with CD and concurrent FGID had higher rates of chronic prescription narcotic use than patients without FGID and to determine the prevalence and risk factors for narcotic misuse in these patient populations.
Narcotic Use and Misuse in CD
depression, substance abuse, prior bowel resection, migraines, and concurrent FGID. A multivariate logistic regression analysis was used to assess the simultaneous effect of these factors on the likelihood of prescription narcotic misuse. The study was approved by the Institutional Review Board at the University of Virginia.
MATERIALS AND METHODS
RESULTS
A retrospective chart review of patients with CD evaluated at the University of Virginia Digestive Health Center outpatient clinic from 2006 to 2011 was performed. Patient demographics including age, gender, race, disability status, tobacco use, and alcohol use were recorded in all patients. Medical, surgical, and psychiatric histories were recorded for all patients. Crohn’s phenotype was recorded using the Montreal classification system. FGID were recorded if there was documentation of an FGID in the medical record by the treating gastroenterologist. All 28 adult FGID diagnoses listed in the Rome III Diagnostic Criteria appendix were looked for. These included the functional esophageal disorders, functional gastroduodenal disorders, functional bowel disorders, functional abdominal pain syndrome, functional gallbladder and sphincter of Oddi disorders, and functional anorectal disorders. Patient medications including narcotic medications were recorded using data from the electronic medical record. Data were collected over a 1-year period. All narcotics were recorded based on narcotic type and whether more than 1 narcotic type was being used. Narcotic types recorded were morphine, oxycodone, hydrocodone, fentanyl, hydromorphone, oxymorphone, methadone, meperidine, propoxyphene, and tapentadol. Codeine and tincture of opium were excluded from this list because these medications may have been used to treat diarrhea in some patients. Chronic narcotic use was defined as monthly narcotic prescriptions filled for 3 consecutive months, or 2 or more narcotic prescriptions filled within a 6-month period. One-time prescription narcotic dispensions postoperatively were not counted. Prescription monitoring program databases from Virginia and West Virginia were accessed to confirm narcotic prescription filling histories for patients in the study cohort. Patient name, date of birth, and the dates seen in clinic were entered into the PMP database, and narcotic prescriptions filled by the patient during the time they were seen in clinic were recorded. The PMP prescription history was used to identify patients with prescription narcotic misuse, using the criteria of 4 or more prescribing physicians and 4 or more pharmacies in the 12-month period (4 + 4).13 If a patient was followed for less than 12 months, then PMP data were collected for the duration the patient was followed. Statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, NC) and GAUSS 13.0 (Aptech Systems, Kent, WA). Comparisons of categorical variables were made using the chi-squared test. The odds ratio (OR) and 95% confidence intervals (CIs) were used to assess the relationship between prescription narcotic misuse and each of the following variables: disability, insurance status, tobacco use, anxiety,
A total of 931 patients with CD were seen at the University of Virginia Digestive Health Clinic over the 6-year period (Table 1). Of these, 87 (9.3%) were identified as having concurrent FGID. Of those with FGID, 84% were documented as having irritable bowel syndrome, 15% with functional abdominal pain, and 1% with functional dyspepsia and functional diarrhea, respectively. None of the other FGID were present. Patients with CD and FGID were younger (41.2 yr versus 45.4 yr without FGID; P ¼ 0.015) and more likely to be female (74% with FGID compared with 54% without FGID; P , 0.001). Additionally, patients with concomitant FGID were more likely to be disabled (15% versus 7%, P ¼ 0.005), use tobacco (38% versus 23%, P ¼ 0.004), and have a concurrent psychiatric disorder (64% versus 23%, P , 0.001). Patients with concomitant FGID were also more likely to have undergone nonIBD abdominal surgery including cholecystectomy (23% versus 11%, P ¼ 0.002) and had nonsignificant trends toward increased rates of appendectomy (15% versus 10%) and hysterectomy (13% versus 7%). Patients with concomitant FGID were also more likely to have nonstricturing nonpenetrating disease phenotypes than those without (63.2% versus 42.5%, P , 0.001). The disease location and proportions of patients with perianal involvement and previous IBD-related surgery were similar between the 2 groups (Table 1). Of the 931 patients reviewed, 192 (20%) were using chronic prescription narcotics. A significantly higher proportion of patients with CD with an FGID were using chronic prescription narcotics (38/87; 44%) compared with non-FGID patients (154/844; 18%, P , 0.001; Table 2 and Fig. 1). Fifteen of 87 (17%) patients with FGID were using 2 or more different types of narcotic medications compared with 5/844 (6%) patients without FGID (Table 2). Chronic prescription narcotic use was associated with higher rates of female gender (66% versus 53%, P ¼ 0.001), disability (16% versus 5%, P , 0.0001), tobacco use (37% versus 22%, P , 0.0001), anxiety (20% versus 7%, P , 0.0001), depression (33% versus 15%, P , 0.0001), substance abuse (6% versus 2%, P ¼ 0.01), migraines (15% versus 5%, P , 0.0001), and FGID (20% versus 6%, P , 0.0001) (Table 3). Using the PMP to review prescription filling histories, evidence of narcotic misuse was found in 113 patients. A significantly higher proportion of patients with FGID were found to be misusing prescription narcotics (32/87; 36.8%) compared with 81/844 (9.6%) in patients without a concomitant FGID (P , 0.001, Fig. 1). Prescription narcotic misuse was associated with higher rates of disability (15% versus 6%, P ¼ 0.001), tobacco use (42% versus 23%, P , 0.0001), anxiety (25% versus 8%, P , 0.0001), depression (38% versus 16%, P , 0.0001), substance abuse www.ibdjournal.org |
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TABLE 1. Characteristics of Patients with CD
Age Female gender, n (%) Race, n (%) White Black Other Disability, n (%) Tobacco use, n (%) Psychiatric disease, n (%) Anxiety Depression Substance abuse CD Montreal classification, n (%) L1 L2 L3 L4 B1 B2 B3 P Previous surgery, n (%) Appendectomy Cholecystectomy Hysterectomy Previous IBD surgery, n (%) Ileocolic/small bowel resection Subtotal colectomy Total colectomy Migraines, n (%) Fibromyalgia, n (%)
CD NonFGID (n ¼ 844)
CD with FGID (n ¼ 87)
45.4 6 15.5 457 (54)
41.2 6 14.0 64 (74)
728 91 25 56 202 197 65 136 21
223 223 383 18 359 261 224 163
(86) (11) (3) (7) (23) (23) (8) (16) (2)
(26.4) (26.4) (45.4) (2.1) (42.5) (30.9) (26.5) (19.3)
78 6 3 13 33 56 26 41 7
27 21 38 1 55 21 11 10
(90) (7) (3) (15) (38) (64) (30) (47) (8)
(31.0) (24.1) (43.6) (1.1) (63.2) (24.1) (12.6) (11.5)
TABLE 2. Chronic Prescription Narcotic Use and Misuse in CD
0.015 ,0.001 0.041 0.376 0.259 0.800 0.005 0.004 0.001 ,0.001 ,0.001 0.004
0.355 0.644 0.761 0.536 ,0.001 0.189 0.004 0.074
85 (10) 96 (11) 63 (7)
13 (15) 20 (23) 11 (13)
0.159 0.002 0.089
282 (33)
26 (30)
0.505
27 96 45 13
(3) (11) (5) (2)
1 5 19 6
(1) (6) (22) (7)
CD Non-FGID (n ¼ 844)
P
0.287 0.108 ,0.001 0.001
Chronic use (total), n (%) Narcotic types, n (%) 1 2 3 4 Narcotic misuse, n (%)
CD with FGID (n ¼ 87)
P
156 (18)
38 (44)
,0.001
113 33 6 0 81
25 12 0 1 32
,0.001 NS NS NS ,0.001
(13) (4) (1) (0) (9.6)
(29) (14) (0) (1) (36.8)
NS, nonsignificant.
DISCUSSION In our study cohort, 20% of patients with CD were using narcotic medications chronically. Several factors were significantly more common in chronic prescription narcotic users, including female gender, disability, smoking, substance abuse, concurrent psychiatric orders, and FGID; all findings that are consistent with previous studies.5,14,15 A notable finding in this cohort was the high rate of chronic prescription narcotic use in patients with CD with a concomitant diagnosis of FGID; over 40% of patients with CD with FGID were using prescription narcotics chronically. In the Crohn’s population, chronic prescription narcotic use is of notable concern given the potential negative impact narcotics have on disease outcomes. Prescription narcotic use is associated with an increased risk of serious infection and mortality in CD4 and may precipitate disease complications through noninflammatory mechanisms, such as increased bowel stasis and compromised immune function. Prescription narcotic use can also mask symptoms of disease complications, including infections and penetrating events, resulting in patients delaying medical care after a complicating event, such as an intra-abdominal abscess. Prescription narcotics also worsen symptoms in patients with FGID through detrimental effects on bowel motility and are thus quite
L1, ileal location; L2, colonic location; L3, ileocolonic location; L4, upper GI tract involvement; B1, nonstricturing nonpenetrating behavior; B2, stricturing behavior; B3, penetrating behavior; P, perianal disease.
(10% versus 2%, P , 0.0001), migraines (13% versus 6%, P ¼ 0.004), and FGID (28% versus 7%, P , 0.0001). Multivariate logistic regression analysis demonstrated a significant association of prescription narcotic misuse with FGID (OR, 3.33; 95% CI, 1.87–5.93). Prescription narcotic misuse was also associated with disability (OR, 2.37; 95% CI, 1.12–5.00), anxiety (OR, 2.16; 95% CI, 1.19–3.94), depression (OR, 1.69; 95% CI, 1.03–2.77), and substance abuse (OR, 3.02; 95% CI, 1.17–7.77). Tobacco use and migraines were not significant predictors for narcotic misuse (Fig. 2).
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FIGURE 1. Chronic prescription narcotic use and misuse in CD.
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Narcotic Use and Misuse in CD
TABLE 3. Chronic Narcotic Use in CD
Female gender, n (%) Race, n (%) White Black Other Disability, n (%) Tobacco use, n (%) Psychiatric disease, n (%) Anxiety Depression Substance abuse Migraines, n (%) Fibromyalgia, n (%) FGID, n (%)
CD with Chronic Narcotic Use (n ¼ 192)
CD Without Chronic Narcotics (n ¼ 739)
P
126 (66)
392 (53)
0.001
159 16 7 31
646 72 21 38
(87) (10) (3) (5)
0.04 NS NS NS ,0.0001
71 (37)
164 (22)
,0.0001
39 (20) 63 (33) 11 (6)
52 (7) 114 (15) 17 (2)
,0.0001 ,0.0001 0.01
28 (15)
36 (5)
,0.0001
9 (5)
10 (1)
0.003
39 (20)
47 (6)
,0.0001
(83) (8) (4) (16)
NS, nonsignificant.
poor treatment options for patients with CD with FGID. A significant concern with prescription narcotic use in patients with chronic nonmalignant conditions, including IBD, is the potential for drug misuse.16 Prescription drug misuse is an increasing problem in the United States with major societal implications. In response to this, PMPs have been implemented in many states and have been shown to reduce rates of clinically inappropriate narcotic prescribing and rates of “doctor shopping.13” Our study found that FGID was a major risk factor for prescription narcotic misuse, with 36% of patients with CD and FGID misusing narcotics. In this study, FGID was strongly associated with prescription narcotic misuse, and this finding persisted after adjusting for other factors, including substance abuse and psychiatric disease. Given that CD is associated with an increased risk of concurrent irritable bowel syndrome and other functional disorders, the population potentially at risk for prescription narcotic misuse is quite large. There are several limitations to this study. This study retrospectively evaluated patients at a single tertiary referral center, and thus the results may not be generalizable to the CD population as a whole. Data regarding clinical disease activity were not consistently reported in the electronic medical record,
FIGURE 2. Patient variables associated with prescription narcotic misuse.
and thus disease activity was not included as a study variable. The patient cohort had a higher prevalence of chronic prescription narcotic use than had been reported in earlier studies.5,15 Although this may be explained by reporting differences between studies, the rates of prescription narcotic use in our patient population are consistent with a recent study13 and likely reflect the overall increase in prescription narcotic use in the United States over the past decade.16 Given the retrospective nature of the study, there may be confounding variables that were not included in the study analysis. Finally, the majority of our patient population resides in Virginia and West Virginia, and thus prescription filling patterns were only monitored by PMPs in these 2 states. It is possible that some patients traveled outside these states for narcotic prescriptions or obtained narcotics from other sources. In conclusion, chronic prescription narcotic use among patients with CD is common and is strongly associated with concomitant FGID. In our cohort, patients with CD with concomitant FGID had a 2-fold increased risk of chronic prescription narcotic use and a 3-fold increased risk of prescription narcotic misuse and thus seem to represent a very high-risk patient population for narcotic-related complications. PMPs can be used to identify patients at particular risk of prescription narcotic misuse.
REFERENCES
1. Schirbel A, Reichert A, Roll S, et al. Impact of pain on health-related quality of life in patients with inflammatory bowel disease. World J Gastroenterol. 2010;16:3168–3177. 2. Long MD, Barnes EL, Herfarth HH, et al. Narcotic use for inflammatory bowel disease and risk factors during hospitalization. Inflamm Bowel Dis. 2012;18:869–876. 3. Docherty MJ, Jones RC, Wallace MS. Managing pain in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:592–601. www.ibdjournal.org |
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4. Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of followup in the TREAT™ registry. Am J Gastroenterol. 2012;107:1409–1422. 5. Cross R, Wilson K, Binion D. Narcotic use in patients with Crohn’s disease. Am J Gastroenterol. 2005;100:2225–2229. 6. Edwards JT, Radford-Smith GL, Florin TH. Chronic narcotic use in inflammatory bowel disease patients: prevalence and clinical characteristics. J Gastroenterol Hepatol. 2001;16:1235–1238. 7. Simren M, Axelsson J, Gillberg R, et al. Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors. Am J Gastroenterol. 2002;97:389–396. 8. Farrokhyar F, Marshall JK, Easterbrook B, et al. Functional gastrointestinal disorders and mood disorders in patients with inactive inflammatory bowel disease: prevalence and impact on health. Inflamm Bowel Dis. 2006;12:38–46. 9. Grunkemeier DM, Cassara JE, Dalton CB, et al. The narcotic bowel syndrome: clinical features, pathophysiology, and management. Clin Gastroenterol Hepatol. 2007;5:1126–1139. 10. Manubay JM, Muchow C, Sullivan MA. Prescription drug abuse: epidemiology, regulatory issues, chronic pain management with narcotic analgesics. Prim Care. 2011;38:71–90.
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11. Gonzalez AM, Kolbasovsky A. Impact of a managed controlled-opioid prescription monitoring program on care coordination. Am J Manag Care. 2012;18:516–524. 12. Baehren DF, Marco CA, Droz DE, et al. A statewide prescription monitoring program affects emergency department prescribing behaviors. Ann Emerg Med. 2010;56:19–23. 13. Katz N, Panas L, MeeLee K, et al. Usefulness of prescription monitoring programs for surveillance- analysis of Schedule II opioid prescription data in Massachusetts, 1996–2006. Pharmacoepidemiol Drug Saf. 2010;19: 115–123. 14. Hanson KA, Loftus EV, Harmsen WS, et al. Clinical features and outcome of patients with inflammatory bowel disease who use narcotics: a case-control study. Inflamm Bowel Dis. 2009;15: 772–777. 15. Dorn SD, Meek PD, Shah ND. Increasing frequency of opioid prescriptions for chronic abdominal pain in US outpatient clinics. Clin Gastroenterol Hepatol. 2011;9:1078–1085. 16. Drossman DA, Creed FH, Oldenc KW, et al. Psychosocial aspects of the functional gastrointestinal disorders. Gut. 1999;45(suppl 2): II25–II30.
Narcotic Use and Misuse in Crohn’s Disease Justin A. Crocker, MD,* Huimin Yu, MD, PhD,* Mark Conaway, PhD,† Anne G. Tuskey, MD,* and Brian W. Behm, MD*
Background: The rate of narcotic misuse in the inflammatory bowel disease population is not well studied. The primary aim of this study was to determine in Crohn’s disease (CD) whether a concurrent functional gastrointestinal disorder (FGID) was associated with increased rates of chronic narcotic use. Second, we aimed to identify potential risk factors for narcotic misuse.
Methods: A retrospective chart review of patients with CD followed at the University of Virginia’s Gastroenterology Clinic from 2006 to 2011 was performed. The prescription monitoring program was accessed to confirm narcotic prescription filling histories. Narcotic misuse was defined as narcotic prescriptions filled from 4 or more prescribers and at 4 or more different pharmacies.
Results: Nine hundred thirty-one patients with CD were included in the study cohort. Eighty-seven (9.3%) patients were identified as having a concurrent FGID, and 192 (20%) were taking chronic narcotics. Patients with FGID were more likely to be taking chronic narcotics (44% versus 18%, P , 0.001). Thirty-seven percent (32/87) of patients with an FGID were misusing narcotics, compared with 9.6% (81/844) (P , 0.0001). Multivariate logistic regression demonstrated a significant association of misuse in patients with a concurrent FGID (odds ratio ¼ 3.33, 95% confidence interval, 1.87–5.93).
Conclusions: Twenty percent of patients with CD were using chronic narcotics with higher rates in those with FGID. Using the prescription monitoring program, a significant proportion of patients with CD with an FGID were misusing narcotics. We would recommend screening for narcotic misuse in patients with CD with a concomitant FGID and consider using prescription monitoring programs to identify others at risk for misuse. (Inflamm Bowel Dis 2014;20:2234–2238) Key Words: Crohn’s disease, functional GI disorders, prescription narcotics
C
rohn’s disease (CD) is a chronic inflammatory disorder characterized by recurring episodes of inflammation in the gastrointestinal tract. Nearly all patients with CD experience abdominal pain during the course of their disease and in some cases are given narcotic medications for symptom management.1,2 Chronic prescription narcotic use has not been shown to be effective in the management of CD and has been associated with increased risk of disease complications, including serious infection and mortality.3,4 Despite these negative effects, patients with CD have been found to have fairly high rates of chronic prescription narcotic use.5,6 CD is also associated with increased rates of functional gastrointestinal disorders (FGID) that can lead to abdominal symptoms in the absence of active intestinal inflammation. The prevalence of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease (IBD) has been shown to be 2 to 3 times higher than that in the general population.7 Some Received for publication June 11, 2014; Accepted July 13, 2014. From the *Division of Gastroenterology, Department of Medicine, University of Virginia, Charlottesville, Virginia; and †Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia. The authors have no conflicts of interest to disclose. Reprints: Brian W. Behm, MD, PO Box 800708, Charlottesville, VA 22908 (e-mail: [email protected]). Copyright © 2014 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1097/MIB.0000000000000194 Published online 9 September 2014.
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studies report over 80% of patients with inactive IBD meet criteria for at least 1 FGID.8 Prescription narcotics generally are poor treatment options for managing pain related to FGID because of the negative narcotic-related effects of intestinal dysmotility and associated visceral hyperalgesia.9 The use of prescription narcotic medications for chronic nonmalignant pain has increased significantly over the past decade in the United States, and over this time, misuse of prescription narcotics has reached epidemic levels.10 Many states have established prescription monitoring programs (PMPs) for narcotic medications, which are online databases that provide a record of each prescription narcotic filled, the quantity dispensed, the prescribing provider, and the filling pharmacy. With these databases, there is less fragmented documentation of narcotic filling patterns in the outpatient setting,11,12 and PMPs have been found to reduce rates of inappropriate narcotic prescribing and misuse.11–13 Behaviors that would suggest prescription narcotic misuse include patients receiving narcotic prescriptions from multiple prescribers, using multiple pharmacies, using multiple narcotic types, and early prescription refills. Although there is not a consensus definition of prescription narcotic misuse, Katz et al13 defined misuse using the criteria of 4 or more prescribers and 4 or more pharmacies in a 12-month period (4 + 4) as concerning for misuse or “doctor shopping.” Prescription narcotic misuse has not been evaluated specifically in the CD patient population to our knowledge. In addition, the prevalence of prescription narcotic use and misuse in Inflamm Bowel Dis Volume 20, Number 12, December 2014
Inflamm Bowel Dis Volume 20, Number 12, December 2014
patients with CD and concomitant FGIDs has not been well studied. The aim of this study was to determine whether patients with CD and concurrent FGID had higher rates of chronic prescription narcotic use than patients without FGID and to determine the prevalence and risk factors for narcotic misuse in these patient populations.
Narcotic Use and Misuse in CD
depression, substance abuse, prior bowel resection, migraines, and concurrent FGID. A multivariate logistic regression analysis was used to assess the simultaneous effect of these factors on the likelihood of prescription narcotic misuse. The study was approved by the Institutional Review Board at the University of Virginia.
MATERIALS AND METHODS
RESULTS
A retrospective chart review of patients with CD evaluated at the University of Virginia Digestive Health Center outpatient clinic from 2006 to 2011 was performed. Patient demographics including age, gender, race, disability status, tobacco use, and alcohol use were recorded in all patients. Medical, surgical, and psychiatric histories were recorded for all patients. Crohn’s phenotype was recorded using the Montreal classification system. FGID were recorded if there was documentation of an FGID in the medical record by the treating gastroenterologist. All 28 adult FGID diagnoses listed in the Rome III Diagnostic Criteria appendix were looked for. These included the functional esophageal disorders, functional gastroduodenal disorders, functional bowel disorders, functional abdominal pain syndrome, functional gallbladder and sphincter of Oddi disorders, and functional anorectal disorders. Patient medications including narcotic medications were recorded using data from the electronic medical record. Data were collected over a 1-year period. All narcotics were recorded based on narcotic type and whether more than 1 narcotic type was being used. Narcotic types recorded were morphine, oxycodone, hydrocodone, fentanyl, hydromorphone, oxymorphone, methadone, meperidine, propoxyphene, and tapentadol. Codeine and tincture of opium were excluded from this list because these medications may have been used to treat diarrhea in some patients. Chronic narcotic use was defined as monthly narcotic prescriptions filled for 3 consecutive months, or 2 or more narcotic prescriptions filled within a 6-month period. One-time prescription narcotic dispensions postoperatively were not counted. Prescription monitoring program databases from Virginia and West Virginia were accessed to confirm narcotic prescription filling histories for patients in the study cohort. Patient name, date of birth, and the dates seen in clinic were entered into the PMP database, and narcotic prescriptions filled by the patient during the time they were seen in clinic were recorded. The PMP prescription history was used to identify patients with prescription narcotic misuse, using the criteria of 4 or more prescribing physicians and 4 or more pharmacies in the 12-month period (4 + 4).13 If a patient was followed for less than 12 months, then PMP data were collected for the duration the patient was followed. Statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, NC) and GAUSS 13.0 (Aptech Systems, Kent, WA). Comparisons of categorical variables were made using the chi-squared test. The odds ratio (OR) and 95% confidence intervals (CIs) were used to assess the relationship between prescription narcotic misuse and each of the following variables: disability, insurance status, tobacco use, anxiety,
A total of 931 patients with CD were seen at the University of Virginia Digestive Health Clinic over the 6-year period (Table 1). Of these, 87 (9.3%) were identified as having concurrent FGID. Of those with FGID, 84% were documented as having irritable bowel syndrome, 15% with functional abdominal pain, and 1% with functional dyspepsia and functional diarrhea, respectively. None of the other FGID were present. Patients with CD and FGID were younger (41.2 yr versus 45.4 yr without FGID; P ¼ 0.015) and more likely to be female (74% with FGID compared with 54% without FGID; P , 0.001). Additionally, patients with concomitant FGID were more likely to be disabled (15% versus 7%, P ¼ 0.005), use tobacco (38% versus 23%, P ¼ 0.004), and have a concurrent psychiatric disorder (64% versus 23%, P , 0.001). Patients with concomitant FGID were also more likely to have undergone nonIBD abdominal surgery including cholecystectomy (23% versus 11%, P ¼ 0.002) and had nonsignificant trends toward increased rates of appendectomy (15% versus 10%) and hysterectomy (13% versus 7%). Patients with concomitant FGID were also more likely to have nonstricturing nonpenetrating disease phenotypes than those without (63.2% versus 42.5%, P , 0.001). The disease location and proportions of patients with perianal involvement and previous IBD-related surgery were similar between the 2 groups (Table 1). Of the 931 patients reviewed, 192 (20%) were using chronic prescription narcotics. A significantly higher proportion of patients with CD with an FGID were using chronic prescription narcotics (38/87; 44%) compared with non-FGID patients (154/844; 18%, P , 0.001; Table 2 and Fig. 1). Fifteen of 87 (17%) patients with FGID were using 2 or more different types of narcotic medications compared with 5/844 (6%) patients without FGID (Table 2). Chronic prescription narcotic use was associated with higher rates of female gender (66% versus 53%, P ¼ 0.001), disability (16% versus 5%, P , 0.0001), tobacco use (37% versus 22%, P , 0.0001), anxiety (20% versus 7%, P , 0.0001), depression (33% versus 15%, P , 0.0001), substance abuse (6% versus 2%, P ¼ 0.01), migraines (15% versus 5%, P , 0.0001), and FGID (20% versus 6%, P , 0.0001) (Table 3). Using the PMP to review prescription filling histories, evidence of narcotic misuse was found in 113 patients. A significantly higher proportion of patients with FGID were found to be misusing prescription narcotics (32/87; 36.8%) compared with 81/844 (9.6%) in patients without a concomitant FGID (P , 0.001, Fig. 1). Prescription narcotic misuse was associated with higher rates of disability (15% versus 6%, P ¼ 0.001), tobacco use (42% versus 23%, P , 0.0001), anxiety (25% versus 8%, P , 0.0001), depression (38% versus 16%, P , 0.0001), substance abuse www.ibdjournal.org |
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TABLE 1. Characteristics of Patients with CD
Age Female gender, n (%) Race, n (%) White Black Other Disability, n (%) Tobacco use, n (%) Psychiatric disease, n (%) Anxiety Depression Substance abuse CD Montreal classification, n (%) L1 L2 L3 L4 B1 B2 B3 P Previous surgery, n (%) Appendectomy Cholecystectomy Hysterectomy Previous IBD surgery, n (%) Ileocolic/small bowel resection Subtotal colectomy Total colectomy Migraines, n (%) Fibromyalgia, n (%)
CD NonFGID (n ¼ 844)
CD with FGID (n ¼ 87)
45.4 6 15.5 457 (54)
41.2 6 14.0 64 (74)
728 91 25 56 202 197 65 136 21
223 223 383 18 359 261 224 163
(86) (11) (3) (7) (23) (23) (8) (16) (2)
(26.4) (26.4) (45.4) (2.1) (42.5) (30.9) (26.5) (19.3)
78 6 3 13 33 56 26 41 7
27 21 38 1 55 21 11 10
(90) (7) (3) (15) (38) (64) (30) (47) (8)
(31.0) (24.1) (43.6) (1.1) (63.2) (24.1) (12.6) (11.5)
TABLE 2. Chronic Prescription Narcotic Use and Misuse in CD
0.015 ,0.001 0.041 0.376 0.259 0.800 0.005 0.004 0.001 ,0.001 ,0.001 0.004
0.355 0.644 0.761 0.536 ,0.001 0.189 0.004 0.074
85 (10) 96 (11) 63 (7)
13 (15) 20 (23) 11 (13)
0.159 0.002 0.089
282 (33)
26 (30)
0.505
27 96 45 13
(3) (11) (5) (2)
1 5 19 6
(1) (6) (22) (7)
CD Non-FGID (n ¼ 844)
P
0.287 0.108 ,0.001 0.001
Chronic use (total), n (%) Narcotic types, n (%) 1 2 3 4 Narcotic misuse, n (%)
CD with FGID (n ¼ 87)
P
156 (18)
38 (44)
,0.001
113 33 6 0 81
25 12 0 1 32
,0.001 NS NS NS ,0.001
(13) (4) (1) (0) (9.6)
(29) (14) (0) (1) (36.8)
NS, nonsignificant.
DISCUSSION In our study cohort, 20% of patients with CD were using narcotic medications chronically. Several factors were significantly more common in chronic prescription narcotic users, including female gender, disability, smoking, substance abuse, concurrent psychiatric orders, and FGID; all findings that are consistent with previous studies.5,14,15 A notable finding in this cohort was the high rate of chronic prescription narcotic use in patients with CD with a concomitant diagnosis of FGID; over 40% of patients with CD with FGID were using prescription narcotics chronically. In the Crohn’s population, chronic prescription narcotic use is of notable concern given the potential negative impact narcotics have on disease outcomes. Prescription narcotic use is associated with an increased risk of serious infection and mortality in CD4 and may precipitate disease complications through noninflammatory mechanisms, such as increased bowel stasis and compromised immune function. Prescription narcotic use can also mask symptoms of disease complications, including infections and penetrating events, resulting in patients delaying medical care after a complicating event, such as an intra-abdominal abscess. Prescription narcotics also worsen symptoms in patients with FGID through detrimental effects on bowel motility and are thus quite
L1, ileal location; L2, colonic location; L3, ileocolonic location; L4, upper GI tract involvement; B1, nonstricturing nonpenetrating behavior; B2, stricturing behavior; B3, penetrating behavior; P, perianal disease.
(10% versus 2%, P , 0.0001), migraines (13% versus 6%, P ¼ 0.004), and FGID (28% versus 7%, P , 0.0001). Multivariate logistic regression analysis demonstrated a significant association of prescription narcotic misuse with FGID (OR, 3.33; 95% CI, 1.87–5.93). Prescription narcotic misuse was also associated with disability (OR, 2.37; 95% CI, 1.12–5.00), anxiety (OR, 2.16; 95% CI, 1.19–3.94), depression (OR, 1.69; 95% CI, 1.03–2.77), and substance abuse (OR, 3.02; 95% CI, 1.17–7.77). Tobacco use and migraines were not significant predictors for narcotic misuse (Fig. 2).
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FIGURE 1. Chronic prescription narcotic use and misuse in CD.
Inflamm Bowel Dis Volume 20, Number 12, December 2014
Narcotic Use and Misuse in CD
TABLE 3. Chronic Narcotic Use in CD
Female gender, n (%) Race, n (%) White Black Other Disability, n (%) Tobacco use, n (%) Psychiatric disease, n (%) Anxiety Depression Substance abuse Migraines, n (%) Fibromyalgia, n (%) FGID, n (%)
CD with Chronic Narcotic Use (n ¼ 192)
CD Without Chronic Narcotics (n ¼ 739)
P
126 (66)
392 (53)
0.001
159 16 7 31
646 72 21 38
(87) (10) (3) (5)
0.04 NS NS NS ,0.0001
71 (37)
164 (22)
,0.0001
39 (20) 63 (33) 11 (6)
52 (7) 114 (15) 17 (2)
,0.0001 ,0.0001 0.01
28 (15)
36 (5)
,0.0001
9 (5)
10 (1)
0.003
39 (20)
47 (6)
,0.0001
(83) (8) (4) (16)
NS, nonsignificant.
poor treatment options for patients with CD with FGID. A significant concern with prescription narcotic use in patients with chronic nonmalignant conditions, including IBD, is the potential for drug misuse.16 Prescription drug misuse is an increasing problem in the United States with major societal implications. In response to this, PMPs have been implemented in many states and have been shown to reduce rates of clinically inappropriate narcotic prescribing and rates of “doctor shopping.13” Our study found that FGID was a major risk factor for prescription narcotic misuse, with 36% of patients with CD and FGID misusing narcotics. In this study, FGID was strongly associated with prescription narcotic misuse, and this finding persisted after adjusting for other factors, including substance abuse and psychiatric disease. Given that CD is associated with an increased risk of concurrent irritable bowel syndrome and other functional disorders, the population potentially at risk for prescription narcotic misuse is quite large. There are several limitations to this study. This study retrospectively evaluated patients at a single tertiary referral center, and thus the results may not be generalizable to the CD population as a whole. Data regarding clinical disease activity were not consistently reported in the electronic medical record,
FIGURE 2. Patient variables associated with prescription narcotic misuse.
and thus disease activity was not included as a study variable. The patient cohort had a higher prevalence of chronic prescription narcotic use than had been reported in earlier studies.5,15 Although this may be explained by reporting differences between studies, the rates of prescription narcotic use in our patient population are consistent with a recent study13 and likely reflect the overall increase in prescription narcotic use in the United States over the past decade.16 Given the retrospective nature of the study, there may be confounding variables that were not included in the study analysis. Finally, the majority of our patient population resides in Virginia and West Virginia, and thus prescription filling patterns were only monitored by PMPs in these 2 states. It is possible that some patients traveled outside these states for narcotic prescriptions or obtained narcotics from other sources. In conclusion, chronic prescription narcotic use among patients with CD is common and is strongly associated with concomitant FGID. In our cohort, patients with CD with concomitant FGID had a 2-fold increased risk of chronic prescription narcotic use and a 3-fold increased risk of prescription narcotic misuse and thus seem to represent a very high-risk patient population for narcotic-related complications. PMPs can be used to identify patients at particular risk of prescription narcotic misuse.
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