Comparing Healthcare Utilization and Costs Among Medicaid-Insured Patients with Chronic Noncancer Pain with and without Opioid-Induced Constipation: A Retrospective Analysis

April 2017 Vol 10, No 2 - Clinical, Original Research
Tope Olufade, PhD, MPH
Director
Health Economics & Outcomes Research
AstraZeneca
Wilmington, DE
Amanda M. Kong, MPH
Research Leader
Truven Health Analytics, an IBM Company
Ann Arbor, MI
Nicole Princic, MS
Manager Research Analyst
Truven Health Analytics, an IBM Company
Bethesda, MD
Paul Juneau, MS
Senior Statistician

Truven Health Analytics, an IBM Company
Bethesda, MD
Rucha Kulkarni, MPH
Research Analyst at the time of this study
Truven Health Analytics, an IBM Company
Bethesda, MD
Kui Zhang, MD
Senior Programmer/Analyst
Truven Health Analytics, an IBM Company
Bethesda, MD
Catherine Datto, MD, MS
US Medical Lead
AstraZeneca
Wilmington, DE
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Abstract

BACKGROUND: Constipation is a common adverse effect of opioid use and has been associated with increased healthcare utilization and costs among patients receiving opioids for pain management.

OBJECTIVE: To compare the healthcare utilization and costs of Medicaid patients with chronic noncancer pain with and without constipation who were receiving opioids.

METHODS: This retrospective, claims-based study was conducted using data from the Truven Health MarketScan Medicaid Multi-State database. Patients with no evidence of cancer who initiated opioid therapy between January 1, 2009, and June 30, 2013, were eligible for the study. Patients had to have continuous enrollment in the database in the 6 months before and 12 months after opioid initiation, with no evidence of substance abuse or functional or inflammatory bowel disease. Medical and pharmacy claims during the 12 months after opioid initiation were evaluated for a diagnosis of constipation or for prescription or over-the-counter medications indicative of constipation. All-cause healthcare utilization and costs were measured over the same period and were compared between propensity score–matched cohorts of patients with evidence of constipation and patients without constipation.

RESULTS: Of the 25,744 patients meeting the study inclusion criteria, 2716 (10.5%) had evidence of constipation. After 1:1 propensity score matching, the 2 cohorts had similar demographic and clinical characteristics (ie, mean age, 47 years; 26%-27% male). During the 12-month follow-up period, healthcare utilization was more frequent among patients with constipation, including inpatient admissions and emergency department visits, than in the matched patients without constipation. The total all-cause mean healthcare costs were substantially higher among the patients with constipation ($28,234; 95% confidence interval [CI], $24,307-$32,160) than in the patients without constipation ($13,709; 95% CI, $12,618-$14,801), with a median cost difference of $4166 per patient (P <.001).

CONCLUSION: Among Medicaid enrollees who receive opioids for chronic noncancer pain, constipation is associated with increased all-cause healthcare utilization and costs.

Key Words: chronic pain, constipation, costs, healthcare utilization, Medicaid, noncancer pain, opioid-­induced constipation, opioids, propensity score matching, side effects

Am Health Drug Benefits.
2017;10(2):79-86
www.AHDBonline.com

Manuscript received October 17, 2016
Accepted in final form February 10, 2017

Supplementary materials online only
Disclosures are at end of text

Chronic noncancer pain is a common and debilitating condition that affects approximately 30% of adults in the United States.1 The management of chronic pain is primarily aimed at relieving the pain and improving physical and emotional functions, although these are not achieved in a substantial number of patients.2 Opioids are among the most frequently prescribed analgesics for the treatment of chronic pain.3,4 Data from controlled clinical trials and observational studies have demonstrated the short-term efficacy of opioids in pain relief.2,5,6 Currently, 4% of adults in the United States are using opioids for chronic noncancer pain.4

Epidemiologic studies indicate that the rate of opioid treatment for chronic pain has exponentially increased in the past 2 decades.7 However, opioid treatment is associated with serious adverse effects, and constipation is one of the most common effects.8-14 A meta-analysis of 15 studies showed that 41% of patients experienced constipation within 8 weeks of starting opioid therapy.9 Opioid-induced constipation adversely affects patients’ health-related quality of life, interfering with opioid medication pain control and resulting in psychological distress and depression.15,16 Several nonpharmacologic methods (ie, increased dietary fiber, fluid intake, and physical activity), pharmacologic agents (eg, stimulants, stool softeners, bulk-forming laxatives, enemas), opioid antagonists (ie, methyl­naltrexone and naloxegol), and a secretagogue (ie, lubiprostone) have been used in clinical practice for the treatment of opioid­induced constipation.4,17,18

Previous US-based analyses have demonstrated higher healthcare utilization and costs in patients who received opioids and have experienced constipation compared with those without constipation.10-14 Of the 5 analyses, 3 were conducted exclusively in patients without cancer.11,13,14 However, these analyses have limitations. They used databases that do not include over-the-counter (OTC) medication claims, defined constipation based on medical claims, and were conducted using older data.10-14 In addition, these analyses mostly focused on commercially insured patients.10,12-14 To date, we know of no analyses that have analyzed the relationship between constipation and healthcare costs specifically among Medicaid-insured patients receiving opioids.

Therefore, the objective of this retrospective study was to focus on the Medicaid population and compare the all-cause healthcare utilization and associated expenditures in patients receiving opioids who had chronic noncancer pain with and without constipation, using recent administrative claims data from the Medicaid database, which included some OTC medication claims.

Methods

This retrospective analysis used administrative healthcare claims data from the Truven Health MarketScan Medicaid Multi-State Database between 2008 and 2014. This database contains inpatient, outpatient, and outpatient prescription drug information for more than 10 million individuals annually from approximately 10 geographically dispersed states that vary in size and sociodemographic composition. All data were deidentified and fully complied with US patient confidentiality requirements (ie, HIPAA) of 1996 and, therefore, Institutional Review Board approval was not sought.

Patient Selection Criteria

Adults (aged ≥18 years) with ≥1 outpatient pharmacy claims for an opioid prescription with a supply of at least 28 days during January 1, 2009, to June 30, 2013, were eligible for inclusion. The date of the first opioid dose was set as the index date. All patients were required to have continuous health plan coverage, with medical and pharmacy benefits at least 6 months before (preperiod) and 12 months after the index date (postperiod). Patients with any outpatient pharmacy claims for opioid or for constipation treatment medications (ie, prescription or OTC) or any medical claims with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code or a Current Procedural Terminology (CPT)-4 or Healthcare Common Procedure Coding System (HCPCS) code that is indicative of constipation (discussed below) during the preperiod were excluded from the study. In addition, patients with cancer (ICD-9-CM 140.xx-239.xx), irritable bowel syndrome (564.1x), ulcerative colitis (556.xx), Crohn’s disease (555.xx), substance abuse and addiction (292.xx, 304.xx, 305.2x-305.9x, 965.xx, V65.42), alcohol abuse and addiction (303.xx, 305.0x), or outpatient pharmacy claims for methadone during the entire study period were also excluded.

Patients were classified into 2 cohorts based on evidence of claims indicative of constipation in the 12 months after the index date. Patients were included in the constipation cohort if they had any of the following points of evidence—a pharmacy claim for an OTC or prescription constipation medication; a medical claim with a diagnosis code for constipation (ICD-9-CM 564.0x), impaction or large bowel obstruction (ICD-9-CM 560.30, 560.32, 560.39, 560.89), or megacolon (ICD-9-CM 564.7x); or a medical claim with a procedure code for an enema or bowel irrigation (ICD-9-CM 96.39; HCPCS E0350, E0532, A4458) or the removal of an impaction (ICD-9-CM 96.38; CPT 45975).

Study Variables

Patient demographic and clinical characteristics. Information on the patients’ demographics, such as age, sex, health plan type, and race, were recorded on the index date. Clinical characteristics, including the Deyo-Charlson Comorbidity Index,19 comorbid conditions (based on the presence of ICD-9-CM diagnosis and procedure codes), and the number of ICD-9-CM diagnosis codes and unique National Drug Codes, were measured during the preperiod. Diagnoses for chronic pain conditions using claims during the preperiod or on the index date, and healthcare utilization and costs during the preperiod, were also recorded.

Healthcare utilization and costs. All-cause healthcare utilization and costs were assessed during the 12-month postperiod for the cohorts with and without constipation. Specific utilization measures included the rates and frequencies of inpatient hospitalization, emergency department visits, outpatient office visits, and other outpatient services (ie, laboratory and radiologic testing, medication infusions) as well as the number of pharmacy prescriptions. The costs for inpatient hospitalizations, emergency department visits, outpatient office visits, and other outpatient services were aggregated as medical services costs. The pharmacy costs were measured separately. The total healthcare costs comprised expenditures incurred as a result of medical services and pharmacy-related expenses. Costs included the total reimbursed amount, including the patients’ deductibles and copayments and the coordination of benefits. All healthcare costs were inflation adjusted to 2014 US dollars using the medical care component of the Consumer Price Index.20

Statistical Analysis

Propensity score matching was used to adjust for baseline differences between patients with and without constipation.21,22 The variables included in a logistic regression model as predictors were age, sex, enrollment in a capitated plan, race, the index opioid type (ie, weak or strong; see Table in the Appendix at the end of this article),14 Deyo-Charlson Comorbidity Index, the preperiod total expenditure, the presence of inpatient admission, the presence of an emergency department visit, the presence of an outpatient office visit, and the presence of a prescription claim in the preperiod with the outcome being the presence of constipation.

Using propensity scores generated from this logistic regression model, patients with constipation were matched 1:1 to patients without constipation based on the greedy algorithm and the nearest neighbor approach, without replacement metric. A standardized difference between the 2 cohorts (mean difference expressed as a percentage of the average standard deviation of the variable’s distribution across the cohorts with and without constipation) of <10% was considered indicative of good balance.

Demographic and clinical characteristics and healthcare utilization and costs were reported for patients with constipation and the matched patients without constipation separately. Categorical variables were reported as counts and percentages. Continuous variables were summarized as means, standard deviations, and medians where appropriate. For cost outcomes, 95% confidence intervals are presented in lieu of standard deviations. Chi-square tests and t-tests were used to calculate potential differences in these distributions between the patients with and without constipation. The Wilcoxon signed-rank sum test, a nonparametric test, was also used for comparison of the all-cause cost and the inpatient cost variables. A critical value of 0.05 was specified a priori as the threshold for statistical significance.

Results

A total of 551,794 potentially eligible patients with at least 1 pharmacy claim for an opioid with at least 28 days’ supply during January 1, 2009, to June 30, 2013, were identified (Figure 1). Of these patients, 25,774 (2716 with constipation, 23,058 without constipation) met the study inclusion criteria. After propensity score matching, 2716 matched pairs of patients were included for analysis.

Figure 1

Table 1 summarizes the demographic and clinical characteristics of patients with constipation and the matched cohort of patients without constipation. The 2 cohorts were similar after matching, indicating that the propensity score matching was successful. The mean age of the patients was 47.3 years for those with constipation and 47.4 years for those without constipation. There were fewer men than women in both cohorts (men with vs without constipation, 27.8% vs 26.2%), and the majority of patients were of white race/ethnicity (patients with vs without constipation, 48.0% vs 47.4%). Overall, the proportions of patients with all-cause healthcare utilization (ie, inpatient admissions, outpatient office visits, other outpatient services, emergency department visits, and pharmacy prescriptions) and healthcare costs during the preperiod were similar in both cohorts.

Table 1

The all-cause healthcare utilization and costs were greater for patients with constipation than for patients without constipation during the 12-month postperiod (Table 2). For example, the proportion of patients with at least 1 inpatient admission was significantly higher among patients with constipation (28.9% vs 13.5% of patients without constipation; P <.001).

Table 2

Among patients with an inpatient admission, the mean length of hospital stay was significantly longer in the cohort with constipation compared with the patients without constipation (7.3 days vs 5.9 days, respectively; P = .014; Table 2). The utilization of other medical services (ie, emergency department visits, outpatient office visits, and other outpatient services) was also more common among the cohort with constipation.

Consistent with healthcare utilization patterns, the total mean healthcare costs during the 12-month follow-up period were substantially higher among patients with constipation ($28,234) than patients without constipation ($13,709); the median cost difference between the matched pairs was $4166. Inpatient and other outpatient-related costs were the primary cost-drivers for both cohorts, consisting of 47.9% and 30.2% of the total cost for patients with constipation and 33.5% and 32.5% for patients without constipation, respectively (Table 2).

Discussion

Among Medicaid enrollees initiating opioid medications for chronic noncancer pain, evidence of constipation was detected in 10.5% of patients within the 12 months after opioid initiation. After matching patients with evidence of constipation to those without constipation, patients with constipation had significantly more healthcare utilization, including inpatient admissions, and therefore, substantially higher healthcare costs. The median incremental cost of constipation was more than $4000 over the 12-month postperiod.

These findings are consistent with other analyses based on different databases conducted previously on opioid use and constipation and other gastrointestinal events, including 5 US-based analyses using claims data that mainly focused on commercially insured patients.10-14 Three of these analyses utilized the PharMetrics database.10-12 More than 75% of the patients in the PharMetrics database were commercially insured.10,12 The earliest of these studies, which was published in 2009, focused on opioid initiators with cancer.10 Constipation was based on diagnosis codes on claims during the 12 months after the initiation of an opioid.10 Candrilli and colleagues reported that healthcare utilization was significantly greater among patients with constipation, as were the average healthcare costs over the 12-month follow-up period.10

Iyer and colleagues found similar results among patients with opioid initiation between 1999 and 2005, regardless of a cancer diagnosis.12 Again, constipation was based on the presence of a diagnosis code of constipation during the 12 months after the initiation of an opioid, and the average costs over 12 months were higher for patients with constipation than for those without constipation for all service categories.12

An analysis of the PharMetrics data by Kwong and colleagues evaluated gastrointestinal events, including nausea and vomiting, constipation, and bowel obstruction, that were identified by diagnosis or by the use of treatment medications, within 3 months after the initiation of an opioid by patients without cancer from 2002 through 2005.11 Patients with evidence of a gastrointestinal event had significantly more healthcare utilization and incurred greater healthcare costs than patients without a gastrointestinal event.11

An analysis conducted by Wan and colleagues using the MarketScan Commercial and Medicare Supplemental databases included patients without cancer who were initiating opioid therapy between 2008 and 2010.13 The patients were required to have been receiving an opioid for at least 90 days.13 Cohorts with constipation were defined by the presence of diagnosis codes in the 12 months after the initiation of an opioid.13 Wan and colleagues found that healthcare costs were significantly higher in patients with constipation than in patients without constipation among nonelderly patients (aged <65 years), elderly patients, and patients in long-term care.13

Finally, Fernandes and colleagues compared the healthcare utilization and costs of commercially insured patients without cancer who did and did not have constipation using HealthCore data.14 Patients who initiated opioids between 2006 and 2013 were included, and the outcomes were evaluated over 12 months, making this the most recent of the published studies we examined.14 The researchers found that the all-cause costs and pain-related costs were significantly higher for patients with constipation.14

Our analysis described here therefore adds to the body of literature by examining Medicaid-covered patients with chronic noncancer pain using recent data, and by defining the cohorts with and without constipation using diagnosis- and medication-related information, including the use of OTC medications that resulted in a claim.

Limitations

Several limitations inherent to claims-based studies apply to our study. First, there is the potential for the misclassification of certain study variables and covariates, because patients were identified through administrative claims data as opposed to medical records. Second, diagnoses on claims may have been coded incorrectly or not coded at all, thereby potentially introducing measurement error. Clinical conditions, including constipation, might not have been included as a diagnosis on a medical claim for a doctor’s visit, or patients may not have sought the care of a healthcare provider for such conditions; therefore, this study is subject to the underreporting of constipation. However, the ability to identify OTC medication use in the Medicaid database may alleviate some potential misclassification of constipation, although not all OTC use of constipation medications is captured.

Substance abuse may also be undercoded, and therefore, it is possible that some patients with substance abuse might have been included in our study.

Third, a proportion of patients with an opioid prescription did not have a diagnosis of a common pain-related condition evaluated in this analysis in their medical claims. Although we assume that these patients were taking an opioid for noncancer pain (because no cancer diagnoses were present), the specific condition for which they were taking an opioid could not be determined. The proportion of patients without a diagnosis of one of the pain conditions evaluated here was similar among patients with (41.0%) and without (44.3%) constipation; therefore, it is unlikely to affect the study’s results. Similarly, previous analyses of patients without cancer have not required patients to have been diagnosed with a pain condition to be included in the analysis.11-14 It is also possible that a patient did not take the opioid despite filling the prescription. This analysis assumes that patients took their medication as directed, but if the patient did not take it and experienced constipation, the constipation would result from another cause.

Although differences between the cohorts were controlled for by propensity score matching, there could be systematic differences between the study cohorts that result from unidentified covariates that partially account for the differences in the study outcomes. Opioid dosing and pain severity were not captured in this analysis, which may have resulted in bias if higher doses or greater pain were associated with an increased risk for constipation, as well as higher healthcare costs, independent of constipation. However, the strength of the initial opioid was included in the propensity score matching and is likely correlated with pain severity. Because exposure and outcomes were measured over the same time period, causal inferences should be made with caution.

Finally, findings from this study pertain to patients with constipation who were enrolled in Medicaid, thereby limiting the generalizability of the findings to patients with other insurance types or populations without health insurance coverage. Despite these limitations, this study has strengths that merit consideration.

Conclusions

This analysis provides contemporary data on healthcare utilization and costs associated with constipation among Medicaid patients receiving opioid treatment for chronic noncancer pain. The inclusion of claims for OTC medications is a strength of this analysis, because many databases do not capture data on OTC medications, which may be the initial (and often only) treatment for constipation in the real-world setting.

Previously published research, primarily in commercially insured populations, has found that constipation is associated with increased healthcare costs among patients receiving opioids. Consistent with those results, this study found that Medicaid-enrolled patients with chronic noncancer pain and constipation who are receiving an opioid had significantly higher healthcare resource utilization and costs compared with patients without constipation.

Appendix

Source of Funding
This study was funded by AstraZeneca.

Author Disclosure Statement
Ms Kong, Ms Princic, Mr Juneau, and Dr Zhang are employees of Truven Health Analytics, which received funding for this study; Ms Kulkarni was an employee of Truven Health Analytics during the study; Dr Olufade and Dr Datto are employees of AstraZeneca.

References
1. Johannes CB, Le TK, Zhou X, et al. The prevalence of chronic pain in United States adults: results of an Internet-based survey. J Pain. 2010;11:1230-1239.
2. Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet. 2011;377:2226-2235.
3. Clark JD. Chronic pain prevalence and analgesic prescribing in a general medical population. J Pain Symptom Manage. 2002;23:131-137.
4. Nelson AD, Camilleri M. Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities. Therap Adv Gastroenterol. 2015;8:206-220.
5. Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006;174:1589-1594.
6. Chou R, Clark E, Helfand M. Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review. J Pain Symptom Manage. 2003;26:1026-1048.
7. Manchikanti L, Helm S II, Fellows B, et al. Opioid epidemic in the United States. Pain Physician. 2012;15(3 suppl):ES9-ES38.
8. Trescot AM, Helm S, Hansen H, et al. Opioids in the management of chronic non-cancer pain: an update of American Society of the Interventional Pain Physicians’ (ASIPP) guidelines. Pain Physician. 2008;11(2 suppl):S5-S62.
9. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112:372-380.
10. Candrilli SD, Davis KL, Iyer S. Impact of constipation on opioid use patterns, health care resource utilization, and costs in cancer patients on opioid therapy. J Pain Palliat Care Pharmacother. 2009;23:231-241.
11. Kwong WJ, Diels J, Kavanagh S. Costs of gastrointestinal events after outpatient opioid treatment for non-cancer pain. Ann Pharmacother. 2010;44:630-640.
12. Iyer S, Davis KL, Candrilli S. Opioid use patterns and health care resource utilization in patients prescribed opioid therapy with and without constipation. Manag Care. 2010;19:44-51.
13. Wan Y, Corman S, Gao X, et al. Economic burden of opioid-induced constipation among long-term opioid users with noncancer pain. Am Health Drug Benefits. 2015;8(2):93-102.
14. Fernandes AW, Kern DM, Datto C, et al. Increased burden of healthcare utilization and cost associated with opioid-related constipation among patients with noncancer pain. Am Health Drug Benefits. 2016;9(3):160-170.
15. Coyne KS, LoCasale RJ, Datto CJ, et al. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014;6:269-281.
16. Dennison C, Prasad M, Lloyd A, et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics. 2005;23:461-476.
17. Kumar L, Barker C, Emmanuel A. Opioid-induced constipation: pathophysiology, clinical consequences, and management. Gastroenterol Res Pract. 2014;2014:141737.
18. Peskin SR, Jackson KC II. Opioid-induced constipation: considerations for formulary decision makers. Am J Pharm Benefits. 2015;7:144-152; quiz, 153.
19. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45:613-619.
20. US Bureau of Labor Statistics. CPI Detailed Report: data for January 2015. www.bls.gov/cpi/cpid1501.pdf. Accessed May 9, 2016.
21. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41-55.
22. D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265-2281.

Portions of this study were presented at ISPOR 21st Annual International Meeting, May 21-25, 2016, in Washington, DC.
Stakeholder Perspective
The Opioid Epidemic: Healthcare Utilization and Cost Considerations
Jack E. Fincham, PhD, RPh
Professor
Department of Pharmaceutical
and Administrative Sciences
Presbyterian College School of Pharmacy
Clinton, SC

The use and misuse of prescription opioid analgesic medications are at an all-time high and are increasing. The negative consequences of this epidemic are many. According to the Centers for Disease Control and Prevention (CDC), 91 Americans die daily from an opioid overdose, including prescription opioids and heroin.1 The opioid crisis is not limited to the United States; it is a North American and Canadian crisis as well, with the Canadian government providing funding to address the problem.2 The CDC has published and promoted prescribing guidelines to help stem inappropriate prescribing of opioids for chronic pain.3

Adverse effects attributable to opioid analgesics are numerous, and the potential for opioid addiction is a prominent concern. Some of the other adverse effects include drowsiness, confusion, disorientation, depression, anxiety, decreased sensitivity to pain relief effects, and opioid-induced constipation. The growing use of opioid medications for chronic pain has led to a dramatic increase in the reporting of opioid-induced constipation.

PATIENTS/PAYERS: The economic impact of opioid-induced constipation can significantly affect payers, patients, and patients’ families. As Olufade and colleagues observe in this issue, patients with constipation associated with opioid use have higher healthcare utilization and costs versus patients who do not have constipation.4 A nationwide study conducted in Denmark comparing the costs of opioid-induced constipation among patients with and without cancer showed that the total healthcare costs were 25% higher for patients with opioid-induced constipation than for those without opioid-induced constipation.5 In a United Kingdom–based study, Wee and colleagues concluded that earlier and/or more effective intervention for opioid-induced constipation in institutional settings could lead to greater clinical and economic benefits.6 Treatments for opioid-induced constipation include over-the-counter options and recently approved prescription medications.7

In addition to the significant economic impact and increased healthcare utilization constipation has, opioid-induced constipation can profoundly affect patients’ quality of life. It is estimated that 17% to 67% of US patients experience constipation when receiving opioids for pain.8 The impact of opioid-induced constipation on patients’ health-related quality of life is likely underestimated.

PROVIDERS/PATIENTS: Perceptions of pain can vary immensely between providers of care and patients. Similarly, quality of life can be evaluated very differently, depending on the perceptions of patients and providers. In an international prospective, longitudinal, observational study of patients aged 18 to 85 years with opioid-­induced constipation, LoCasale and colleagues observed a significant discordance between the perceptions of healthcare providers and patients regarding the symptoms of constipation, laxative use and effectiveness, and the negative effects of constipation on the patient’s quality of life.8 They concluded that the negative effects of opioid-induced constipation on quality of life were not fully appreciated by healthcare providers.8 Furthermore, in a Swedish study, Hjalte and colleagues found that the total per-patient per-month (PPPM) costs for patients with severe constipation were significantly higher than the PPPM costs for those with mild, moderate, or no constipation. They concluded that the potential negative effects of constipation after opioid use for chronic pain can severely limit the benefits of effective pain therapy.9

Overall, the direct and indirect costs of opioid-induced constipation are substantive, are undermeasured, and unappreciated. Much research is needed to elucidate opioid use and dependence, as well as the economic and quality-of-life impacts associated with the side effects of opioid-based analgesic therapies.

1. US Centers for Disease Control and Prevention. Drug overdose deaths in the United States continue to increase in 2015. www.cdc.gov/drugoverdose/epidemic. Accessed March 27, 2017.
2. Health Canada. Government of Canada announces $6 million in emergency funding to combat opioid crisis in Alberta. Press release. March 10, 2017. www.canada.ca/en/health-canada/news/2017/03/government_of_canadaannounces 6millioninemergencyfundingtocombato.html. Accessed March 27, 2017.
3. US Centers for Disease Control and Prevention. CDC Guideline for Prescribing Opioids for Chronic Pain. www.cdc.gov/drugoverdose/prescribing/guideline.html. Accessed March 28, 2017.
4. Olufade T, Kong AM, Princic N, et al. Comparing healthcare utilization and costs among Medicaid-insured patients with chronic noncancer pain with and without opioid-induced constipation: a retrospective analysis. Am Health Drug Benefits. 2017;10(2):79-86.
5. Søndergaard J, Christensen HN, Ibsen R, et al. Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy: a nationwide register-based cohort study in Denmark. Scand J Pain. 2017;15:83-90.
6. Wee B, Adams A, Thompson K, et al. How much does it cost a specialist palliative care unit to manage constipation in patients receiving opioid therapy? J Pain Symptom Manag. 2010;39:644-654.
7. Twycross R, Sykes N, Mihalyo M, et al. Stimulant laxatives and opioid-­induced constipation. J Pain Symptom Manage. 2012;43:306-313.
8. LoCasale RJ, Datto C, Wilson H, et al. The burden of opioid-induced constipation: discordance between patient and health care provider reports. J Manag Care Spec Pharm. 2016;22:236-245.
9. Hjalte F, Berggren A, Bergendahl H, Hjortsberg C. The direct and indirect costs of opioid-induced constipation. J Pain Symptom Manage. 2010;40:696-703.

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