Journal of Pain and Symptom Management
Volume 36, Issue 1 , Pages 39-45, July 2008

Pain, Substance Use Disorders and Opioid Analgesic Prescription Patterns in Veterans with Hepatitis C

  • Ashlee J. Whitehead, MA, LPC, CADC

      Affiliations

    • Northwest Hepatitis C Resource Center
    • Behavioral Health & Clinical Neurosciences Division
    • Corresponding Author InformationAddress correspondence to: Ashlee Whitehead, MA, LPC, CADC, Portland VA Medical Center, 3710 Southwest U.S. Veterans Hospital Road, Portland, OR 97207, USA.
    • ,
  • Steven K. Dobscha, MD

      Affiliations

    • Behavioral Health & Clinical Neurosciences Division
    • Columbia Center for the Study of Chronic, Comorbid Mental and Physical Disorders
    • Department of Psychiatry, Oregon Health & Science University, Portland, Oregon
    • ,
  • Benjamin J. Morasco, PhD

      Affiliations

    • Northwest Hepatitis C Resource Center
    • Behavioral Health & Clinical Neurosciences Division
    • Department of Psychiatry, Oregon Health & Science University, Portland, Oregon
    • ,
  • Samantha Ruimy, BS

      Affiliations

    • Northwest Hepatitis C Resource Center
    • Behavioral Health & Clinical Neurosciences Division
    • ,
  • Cara Bussell, BA

      Affiliations

    • Northwest Hepatitis C Resource Center
    • Behavioral Health & Clinical Neurosciences Division
    • ,
  • Peter Hauser, MD

      Affiliations

    • Northwest Hepatitis C Resource Center
    • Behavioral Health & Clinical Neurosciences Division
    • J.E.N.S. Lab, Portland VA Medical Center
    • Department of Psychiatry, Oregon Health & Science University, Portland, Oregon
    • Department of Behavioral Neurosciences, Oregon Health & Science University, Portland, Oregon
    • Department of Internal Medicine, Oregon Health & Science University, Portland, Oregon

Accepted 15 August 2007. published online 25 March 2008.

Article Outline

Abstract 

To examine the prevalence of pain, substance use disorder (SUD) diagnoses, and opioid analgesic prescription patterns among veterans infected with the hepatitis C virus (HCV), a retrospective review of the medical records of 8,224 HCV-positive (HCV+) veterans was performed. Twenty-nine percent and 46% of HCV+ patients were prescribed opioids in the prior one and three years, respectively. Sixty-seven percent of HCV+ patients had documented pain diagnoses and 56% had SUD diagnoses. Patients with co-occurring pain and SUD were less likely to be prescribed opioids than patients with pain only (prior year: 36% vs. 43%, P<0.001; three years: 56% vs. 60%, P<0.01). There were no differences in numbers of early opioid prescription fills or numbers of opioid prescribers when comparing patients with co-occurring pain and SUD to patients with pain only. Veterans with co-occurring pain and opioid use disorder had fewer early opioid fills than veterans with pain only (prior year: 2.6 vs. 5.3 days, P<0.01; three years: 6.1 vs. 13.4 days, P<0.001). These data demonstrate that pain and SUD diagnoses were common among HCV+ patients, and that opioids were frequently prescribed. Co-occurring SUD was not associated with indicators of prescription opioid misuse.

Key Words: Opioids, hepatitis C, pain management, medication misuse, veterans

 

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Introduction 

An estimated 1.8% of the U.S. population and 5.4% of veterans who access Veterans Affairs (VA) Medical Centers are infected with the hepatitis C virus (HCV).1, 2 HCV is the most common chronic blood-borne infection in the United States and a major cause of cirrhosis and hepatocellular carcinoma.1 Chronic HCV is also commonly associated with extrahepatic symptoms, including nonmalignant pain conditions such as musculoskeletal pain and rheumatic manifestations such as arthritis, arthralgias, and fatigue.3, 4 These conditions have been identified in up to 36% of HCV patients.5, 6, 7 In one study of patients attending a university-based hepatology clinic over a seven-month period, musculoskeletal pain and fatigue were reported by 81% of HCV patients, compared to 56% of patients without HCV.8

Opioid analgesics are increasingly being prescribed in the treatment of chronic nonmalignant pain.9 For instance, in a nationally representative survey of outpatient physician visits comparing data from 1980 and 2000, opioid prescriptions increased for acute pain (8% vs. 11%) and doubled for chronic pain (8% vs. 16%). The prescribing of opioids such as hydrocodone, oxycodone, and morphine during outpatient visits for chronic musculoskeletal pain increased from 2% to 9% of visits.10 In a recent study of 300 randomly selected VA patient charts, 50% of veterans had at least one chronic pain diagnosis and 75% of these veterans received an analgesic prescription, nearly half of which were opioids.11 However, in this study, patients with HCV were not identified.

Despite this change in prescribing patterns, controversy exists regarding the long-term use of opioid analgesics for chronic nonmalignant pain.12, 13 There is a paucity of literature confirming long-term safety and efficacy, including a lack of studies examining the prevalence, benefits and consequences of opioid treatment in HCV populations.

Use of opioid analgesic medications in HCV patients is of major concern to clinicians given the high rates of co-occurring substance use disorder (SUD) in these patients when compared to the general population.14, 15, 16 Co-occurring HCV and SUD is particularly common among veterans treated within VA Medical Centers, with 58%–69% of veterans with HCV also having SUD.17, 18, 19 It is estimated that 50%–90% of intravenous drug users are infected with HCV.20 Also, one study suggests that both intranasal drug users and individuals who are alcohol dependent are at increased risk for HCV infection.21

The treatment of chronic pain with opioids in patients with SUD is controversial.22, 23 However, current medical practice recognizes that substance use disorders should not necessarily exclude someone from being prescribed opioid analgesics.24 Given that a high proportion of HCV patients often have chronic pain and SUD, the objective of the study was to assess pain and SUD prevalence and opioid analgesic prescription patterns among veterans with HCV in a regional Veterans Integrated Service Network (VISN). We hypothesized that HCV+ veterans with SUD would be more likely to have pain-related diagnoses (PRDs), receive opioids, and have indicators of potential opioid misuse (more early opioid prescription fills and more prescribers of opioids) than HCV+ veterans without SUD.

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Methods 

Data Sources 

We collected data on patients seen at any facility within VISN 20. VISN 20 encompasses eight medical centers and 17 outpatient clinics in a four-state area that includes Alaska, Idaho, Oregon, and Washington. Data came from the VISN 20 Data Warehouse, a collection of databases extracted from the electronic patient medical records at each facility. Reliability checks are performed regularly. The project was approved by the VA Institutional Review Board.

Data Definitions 

HCV Status: Using laboratory-testing results, we identified all patients over a five-year period (from January 1, 2000 through December 31, 2004) who were antibody positive for HCV, which was confirmed by polymerase chain reaction (PCR) results. We considered patients HCV+ if their most recent HCV PCR lab result was positive. Patients with a positive HCV antibody test, but without a detectable HCV viral load by PCR, were excluded from this analysis. We excluded veterans who died prior to January 1, 2006 (to exclude individuals who may have been at the end of life, and therefore, prescribed opioid analgesics at a higher rate or for malignant/cancer pain) and nonveterans who did not receive regular care from the VHA but had records in the system (i.e., VHA employees, veterans’ family members, or patients receiving care for humanitarian emergencies).

History of Chronic Nonmalignant Pain-Related Diagnosis: We considered patients to have nonmalignant PRD if their records included an ICD-9 code for a PRD. Pain-related subgroups included neuropathies (250.6x, 353.5, 355.xx, 356.xx, 357.xx, 337.1); headache (784.0); migraine (346.9); inflammatory bowel disease (558.9), chronic low back pain (722.xx, 724.xx); rheumatism/arthritis (712.xx, 714.xx, 715.xx, 716.xx, 720.xx, 729.xx); and chronic neck or joint pain/arthropathy (717.xx, 716.xx, 718.xx, 719.xx, 723.xx, 729.xx).

History of Opioid Use Disorders: We considered patients to have opioid abuse or dependence (OAD) if their records included an ICD-9 code for an OAD use disorder (304.xx, 305.5x).

History of Substance Use Disorder: We considered patients to have SUD if their records included an ICD-9 code for any SUD diagnosis. In addition to OAD, SUD subgroups included alcohol (305.0x, 303.9x); amphetamine (304.4x, 305.7x), cannabis (304.3x, 305.2x), cocaine (304.2x, 305.6x); and hallucinogen (304.5x, 305.3x) use disorders. We did not include caffeine or nicotine-related disorders.

Opioid Analgesic Prescriptions: Prescription information included data from 2002 to 2004. We recorded opioid analgesic prescriptions written through the VA outpatient pharmacies. Medication subgroups included codeine, fentanyl, hydrocodone, hydromorphone, morphine, oxycodone, and propoxyphene. We did not include methadone as it is commonly prescribed for maintenance of opioid withdrawal and could confound the analyses. Opioid prescriptions were identified for the previous 12-month (one year) and 36-month (three year) intervals. Opioid prescription pattern measures included number of patients receiving opioids, number of days that patients received opioid fills early, and number of different providers prescribing opioids per patient. Early fills were counted by calculating the average number of days that the fills were early, summed up over all fills in each medication subgroup for each patient.

Antiviral Treatment for Hepatitis C: We identified patients with interferon therapy prescriptions written since 2002 through the VA outpatient pharmacies. These patients were included in the analyses.

Statistical Analyses 

Odds ratios were calculated using logistic regression models to determine whether PRD, opioid prescription rates, or other demographic characteristics differed based on the presence of SUD. T-tests were conducted to determine whether early fills or average number of opioid prescribers differed on the basis of PRD, SUD, and OAD.

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Results 

Demographic Characteristics 

A total of 9,359 veterans had a positive HCV antibody test result and PCR confirmation between January 2000 and December 2004. Approximately 12% (n=1,152) of this sample was deceased prior to January 1, 2006; their data were excluded, leaving 88% (n=8,224) of subjects for analyses. Descriptive statistics for the total sample are summarized in Table 1. Sixty-seven percent of HCV+ veterans had at least one documented PRD. The frequency of PRD in order of prevalence was arthropathy (40%), low back pain (38%), rheumatism/arthritis (33%), headache (9%), neuropathy (8%), migraine (3%), and inflammatory bowel disease (2%). Of those with a PRD, 60% carried two or more diagnoses. Over half (56%) of HCV+ veterans had an SUD. The frequency of SUD in order of prevalence was alcohol (52%), cocaine (16%), cannabis (13%), opioid (13%), amphetamine (8%), and hallucinogen (<1%). Of those with an SUD, 56% had two or more SUD disorders. Of veterans receiving opioids in the past three years, the most common PRDs were neuropathy (69%), headache (67%), rheumatism/arthritis (65%), low back pain (64%), migraine (64%), arthropathy (63%), and inflammatory bowel disease (60%).

Table 1. Demographic Characteristics of Veteran Patients with Hepatitis C (diagnosed 2000–2004) Within the Northwest Veterans Integrated Service Network (VISN 20)
Total Sample HCV PCR+n=8,224
Mean age±SD54±6.9

Gender
Male7,978 (97%)
Female246 (3%)

Race, not recorded3,426 (41.7%)
Race, recorded4,798 (58.3%)
Caucasian3,817 (79.6%)
Non-Caucasian981 (20.4%)

History of PRD5,471 (66.5%)
History of any SUD4,601 (55.9%)
History of OAD1,046 (12.7%)

Received OAP
Past year (Jan 2004–Dec 2004)2,463 (29.9%)
Past three years (Jan 2002–Dec 2004)3,749 (45.6%)

Received IFN for HCV; Past three years (Jan 2002–Dec 2004)500 (6.1%)

SD=standard deviation; OAP=opioid analgesic prescription; IFN=interferon therapy.

Thirty percent of HCV+ veterans had received opioid analgesic prescriptions in the previous one year, and 46% had received opioids in the previous three years. The type of opioids HCV+ veterans received over the previous one-year and three-year periods in order of prevalence were hydrocodone (16% and 28%), oxycodone (13% and 22%), codeine (6% and 13%), morphine (5% and 7%), propoxyphene (0.7 and 2%), fentanyl (0.4% and 0.9%), and hydromorphone (0.4% and 0.7%). Of those receiving opioids, 29% had received two or more types of opioids in the past year and 43% received two or more types of opioids over the past three years.

Comparison of HCV+ Veterans With and Without SUD 

Table 2 provides a summary of the relationship between demographic variables and presence or absence of an SUD. Compared to HCV+ veterans with no SUD, veterans with SUD were significantly more likely to have PRD (69.1% vs. 63.2%, P<0.001) including: arthropathy (42.1% vs. 36.5%, P<0.001), low back pain (40.4% vs. 34.5%, P<0.001), rheumatism/arthritis (33.8% vs. 30.9%, P<0.01), and irritable bowel disease (2.7% vs. 1.8%, P<0.05).

Table 2. Odds Ratios of HCV+ Patients with and without SUD by Demographic Characteristics
SUD (n=4,601)No SUD (n=3,623)OR95% CIP
Gender
Male4,500 (97.8%)3,478 (96.0%)1.891.46–2.45<0.001
Female100 (2.2%)146 (4.0%)

Race
Caucasian2,424 (79.0%)1,393 (80.5%)0.920.79–1.060.235
Non-Caucasian643 (21.0%)338 (19.5%)

Pain-related diagnosis
Any3,179 (69.1%)2,292 (63.2%)1.301.19–1.43<0.001
Arthropathy1,937 (42.1%)1,321 (36.5%)1.271.16–1.39<0.001
Low back1,860 (40.4%)1,250 (34.5%)1.291.18–1.41<0.001
Rheumatism/arthritis1,554 (33.8%)1,119 (30.9%)1.141.04–1.25<0.01
Headache428 (9.3%)305 (8.4%)1.120.96–1.300.16
Neuropathies365 (7.9%)267 (7.4%)1.080.92–1.280.34
Migraine117 (2.5%)104 (2.9%)0.880.68–1.160.36
Irritable bowel disease122 (2.7%)66 (1.8%)1.471.09–1.99<0.05

Opioid analgesic prescriptions
Past one year1,303 (28.3%)1,160 (32.0%)0.840.76–0.92<0.001
Past three years2,091 (45.4%)1,658 (45.8%)0.990.91–1.080.78

Receiving interferon therapy (Jan 2002–Dec 2004)227 (4.9%)273 (7.5%)0.640.53–0.76<0.001

t P
Mean Age (SD)53.1 (± 5.9)55.3 (± 7.8)14.48 <0.001

OR=odds ratio; 95% CI=95% confidence interval; SD=standard deviation.

Reference group: No history of SUD.

Compared to HCV+ veterans with no SUD, veterans with SUD were significantly less likely to have received opioid analgesic prescriptions in the past year (28.3% vs. 32.0%, P<0.001) but there was no difference in the past three years (45.4% vs. 45.8%, P=ns).

Opioid Prescription Patterns and Early Prescription Fills 

Table 3 provides a summary of opioid prescription patterns in HCV+ veterans with PRD according to SUD status. HCV+ veterans with PRD and SUD were significantly less likely to receive opioid prescriptions than HCV+ veterans with PRD and no SUD over the past year (36.0% vs. 42.9%, P<0.001) and past three years (56.0% vs. 59.6%, P<0.01). Of the HCV+ veterans with PRD who received opioids, there were no significant differences in either early opioid prescription fills over the previous one year (4.7 vs. 5.2 days, P=0.27) and three years (11.6 vs. 13.6 days, P=0.09), or number of different opioid prescribers (4.7 vs. 4.4 prescribers, P=0.07) in those with as compared to those without an SUD.

Table 3. Opioid Analgesic Prescription Fills and Early Fill Statistics in HCV Patients with Co-occurring Pain Related Diagnosis (PRD) and Substance Use Disorder (SUD)
PRD + SUD (n = 3179)PRD no SUD (n = 2292)OR95% CIp
Opioid analgesic prescriptions
Past 1 year36.0%42.9%0.750.67–0.83<0.001
Past 3 years56.0%59.6%0.870.78–0.97<0.01
Those who received opioids onlyPRD + SUD (n = 1143)PRD no SUD (n = 983)t p
Average days early opioid fills
Past 1 year (SD)−4.7 (± 12.4)−5.2 (± 11.6)−1.11 0.27
Past 3 years (SD)−11.6 (± 26.6)−13.6 (± 28.0)−1.72 0.09
Average number of opioid prescribers in the past 3 years (SD)4.7 (± 4.2)4.4 (± 3.7)−1.83 0.07

OR=odds ratio; 95% CI=95% confidence interval; SD=standard deviation.

Table 4 provides a summary of opioid prescription patterns in HCV+ veterans with PRD according to OAD status. HCV+ veterans with PRD and OAD had significantly fewer early opioid prescription fills than HCV+ veterans with PRD and no OAD over the past one year (−2.6 vs. −5.3 mean days early, P<0.01) and past three years (−6.1 vs. −13.4 mean days early, P<0.001). However, HCV+ veterans with PRD and OAD had significantly more opioid prescribers than HCV+ veterans with PRD and no OAD (5.6 vs. 4.5 prescribers, P<0.001). There was no significant difference in number of opioid analgesic prescriptions over the previous one or three years in HCV+ veterans with PRD based on the presence or absence of an OAD.

Table 4. Opioid Analgesic Prescription Fill and Early Fill Statistics in HCV Patients with Co-occurring Pain Related Diagnosis (PRD) and Opioid Use Disorder (OAD)
PRD + OAD (n = 731)PRD no OAD (n = 4740)OR95% CIp
Opioid analgesic prescriptions
Past 1 year36.1%39.3%0.870.74–1.030.10
Past 3 years58.3%57.4%1.040.89–1.22
Those who received opioids onlyPRD + OAD (n = 264)PRD no OAD (n = 1862)t p
Average days early opioid fills
Past 1 year (SD)−2.6 (± 8.6)−5.3 (± 12.4)−3.35 <0.01
Past 3 years (SD)−6.1 (± 16.1)−13.4 (± 28.4)−4.08 <0.001
Average number of opioid prescribers in the past 3 years (SD)5.6 (± 5.0)4.5 (± 3.8)−4.43 <0.001

OR=odds ratio; 95% CI=95% confidence interval; SD=standard deviation.

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Discussion 

In the current study, we used archival data from a regional computerized patient record system to examine prevalence of pain-related and SUD diagnoses, and describe opioid analgesic prescription patterns among veterans with HCV. Over two-thirds of patients in the sample suffered from at least one PRD and over half were prescribed opioids. Co-occurring SUD was not found to be associated with indicators of potential opioid misuse.

Our study supports previous findings indicating that HCV+ patients often have co-occurring pain and SUD4, 8, 25, 26 and are often prescribed opioids for chronic pain.10 It is possible that prescribing opioid analgesics to relieve pain is preferred by clinicians as there is less risk than potentially hepatotoxic analgesics such as nonsteroidal anti-inflammatory drugs, which are used with caution in HCV patients with chronic liver disease.27 A possible exception is morphine, which has been shown to upregulate HCV replication in vitro28 and exhibits a much longer half-life in cirrhotic patients.29

Previous studies have shown that providers may be less likely to prescribe opioids for nonmalignant pain in patients who have a history of SUD due to concerns about promoting addictive or aberrant drug-taking behaviors.30 Patients with a history of SUD may also be more likely to seek opioids secondary to their addiction.31 In this study, patients with SUD were more likely to have PRD; however, among patients with PRD, those with SUD were prescribed opioids at lower rates than those without SUD. Additionally, patients with PRD and SUD who were prescribed opioids did not fill prescriptions earlier or have more opioid prescribers than those with PRD and no SUD, both common clinical indicators of pain medication misuse.32, 33, 34 Finally, patients with a specific history of opioid use disorders had significantly fewer early fills of opioids. Together these findings suggest that, although the prescribing of opioid analgesics in HCV+ patients with SUD is common, patients with SUD may not be more likely to exhibit prescription opioid misuse than patients without SUD. Indeed, that patients with SUD are less likely to receive opioids for pain even though they more frequently have PRD, suggests a possibility that patients with SUD may be at risk for undertreatment of pain.

There are several limitations to our study. First, PRD and SUD classifications are based on ICD-9 codes collected from medical records. In the case of SUD, ICD-9 codes do not accurately discriminate between active and remitted SUD. Second, there was no matched HCV-negative comparison group, and it is unclear how the patterns of opioid prescriptions identified in this study with HCV+ patients differ from other medical populations. Third, the study sample is fairly homogenous (a high proportion were Caucasian male veterans), which may limit generalizability of the study findings. Fourth, we did not use a validated measure of prescription opioid misuse, relying instead on common clinical indicators. It is possible that increased numbers of early fill days, for example, could reflect more changes in treatment regimens rather than overuse of medication by patients. Veterans may procure opioid analgesics from sources other than VA pharmacies and these prescriptions would be missed in the analyses. Additionally, prescribing practices, as well as veterans’ preference to use opioid analgesics for pain treatment, may vary. Finally, our decision to remove veterans who were deceased from the sample may have biased results toward veterans with less general medical and SUD-related morbidity. However, a strength of our study is the large sample size of HCV+ patients from a regional health care network database.

In conclusion, PRD and SUD are common among veterans who are HCV+, and opioids are frequently prescribed. SUD, overall, does not appear to be a predictor of early fills or receiving prescriptions from multiple VA clinicians. Future directions for research include examining the characteristics and correlates of pain in patients with HCV; exploring factors that guide clinicians’ decisions about prescribing opioid medications, especially in populations with high SUD co-occurrence; and developing and validating measures of aberrant opioid behaviors in high-risk populations.

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PII: S0885-3924(08)00063-8

doi:10.1016/j.jpainsymman.2007.08.013

Journal of Pain and Symptom Management
Volume 36, Issue 1 , Pages 39-45, July 2008

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