The Journal — October 2018
Tex Med. 2018;114(10):e1.
By John C. Licciardone, DO, MS, MBA1 (corresponding author), Robert J. Gatchel, PhD, ABPP2, and Subhash Aryal, PhD3
1. Department of Family Medicine, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107
2. Department of Psychology, University of Texas at Arlington, 701 South Nedderman Drive, Arlington, TX 76019
3. Department of Biostatistics and Epidemiology and Institute for Patient Safety, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107
Support: This study was supported in part by the Osteopathic Heritage Foundation and the Institute for Patient Safety. None of the funding bodies had a role in the design of the registry, the collection, analysis, or interpretation of the data, or in writing the manuscript.
Acknowledgements: The authors wish to thank the registry research staff for their contributions to the study.
Conflicts of interest: The authors declare that they have no competing interests.
Measuring treatments used by 202 patients with chronic low back pain in the PRECISION Pain Research Registry, this study determined the associations of opioid and nonsteroidal anti-inflammatory drug (NSAID) therapy with clinical status. More than one-fourth of patients did not use nonpharmacologic treatments for low back pain. Patients age 50-59 and 60-79 years old were more likely to use opioids than younger patients. Patients using opioids reported greater pain and back-related disability than did patients using NSAIDs. Patients concurrently using opioids and NSAIDs reported greater back-related disability and poorer quality of life than did patients using no or other pharmacologic therapy. No significant associations between pharmacologic therapy and clinical status remained after controlling for potential confounders.
Neither opioids nor opioids combined with NSAIDs were more effective than just NSAIDs. Greater use of nonpharmacologic therapies and better second-line, nonopioid pharmacologic therapies appear necessary for more effective treatment of chronic low back pain.
The Centers for Disease Control and Prevention (CDC) have reported that the United States is experiencing an epidemic of drug-overdose deaths, driven largely by increasing mortality rates attributable to the use of opioid pain relievers and heroin since 2000.1 In response, it published the “CDC Guideline for Prescribing Opioids for Chronic Pain.”2 The guideline recommends initiating treatment for chronic pain with nonpharmacologic therapy and nonopioid pharmacologic therapy, and prescribing opioids only if the expected benefits in pain and functioning outweigh the risks to the patient. Further, the guideline recommends that if opioids are prescribed, they be combined with nonpharmacologic and nonopioid pharmacologic therapy, as appropriate.
Promotional efforts were undertaken in conjunction with the Office of the Surgeon General to disseminate the CDC guideline, including a pocket card mailed to 2.3 million health care professionals asking them to address the epidemic.3 The “Turn the Tide Rx” pocket guide provided comprehensive information on prescribing opioids for chronic pain, highlighting that opioids generally should not be prescribed as the first-line therapy for chronic pain. The pocket card also addressed assessment of pain and functioning prior to opioid prescribing, appropriate daily morphine milligram equivalent dosing, and when and how to tailor taper rates for individual patients.
The American College of Physicians subsequently published its updated guideline on noninvasive treatments for low back pain.4 This guideline generally reaffirmed the CDC recommendations by advocating that patients with chronic low back pain initially use such nonpharmacologic treatments as exercise, acupuncture, yoga, cognitive behavioral therapy, and spinal manipulative therapy. It recommended pharmacologic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line pharmacologic therapy in patients with an inadequate response to nonpharmacologic therapy. Tramadol or duloxetine were recommended as second-line pharmacologic therapy before considering opioids. Opioids were recommended only as a last option if their potential benefits outweigh the risks for individual patients.
In light of these clinical practice guidelines, the purpose of this study was to use a community-based pain research registry to measure nonpharmacologic and pharmacologic treatments used by patients with chronic low back pain, and to determine the associations of opioid and NSAID therapy with pain and related functioning, quality-of-life, and psychosocial measures.
Registry overview and study design
This study was conducted within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION), which was launched at the University of North Texas Health Science Center (UNTHSC) in April 2016. The registry was designed using principles delineated by the Agency for Healthcare Research and Quality for evaluating patient outcomes.5 Details regarding registry creation and operations have been reported.6 The registry currently enrolls patients with subacute and chronic low back pain by recruiting from local clinics, community organizations, and the general population within the Dallas-Fort Worth Metroplex. The registry and study protocol were approved by the UNTHSC Institutional Review Board (#2015-169), and all patients provided written informed consent prior to participation. This study includes patients with chronic low back pain who enrolled in the PRECISION Pain Research Registry through December 2017. The entire study period followed publication of the “CDC Guideline for Prescribing Opioids for Chronic Pain.”2
Inclusion and exclusion criteria
Study patients were selected from the registry using the case definition established by the NIH Task Force on Research Standards for Chronic Low Back Pain.7 It defines chronic low back pain as that which has persisted at least three months and that has resulted in pain on at least half of the days in the past six months. Patients were required to be 21 or older to participate. Women who reported being pregnant and institutionalized persons were excluded from the study.
Data collection and survey instruments
A comprehensive series of data elements and validated research instruments were completed by patients upon enrolling in the registry. The Qualtrics software (Provo, UT) was used to collect these data using English-language survey items. The National Institutes of Health (NIH) minimum dataset was used to gather information on the demographic characteristics, medical history, symptoms, and functioning of patients.7 An inventory of 10 back-related and general medical conditions was used to identify current or previous comorbidities, including herniated disc, sciatica, osteoporosis, osteoarthritis, heart disease, hypertension, diabetes mellitus, asthma, bronchitis, and depression. Similarly, an inventory of common nonpharmacologic treatments was administered to identify current or previous therapies used for low back pain, including an exercise therapy program, yoga, spinal manipulative therapy, acupuncture, and cognitive behavioral therapy. Information was collected on all medications used, as well as those used specifically for low back pain. Opioids were defined so as to align with the NIH minimum dataset (item 13), which includes tramadol and combination drugs (e.g., opioid and acetaminophen).7 The Pain Catastrophizing Scale was used to measure the phenomenon defined as “an exaggerated negative mental set brought to bear during actual or anticipated painful experience.”8 Total scores on this scale range from 0 (no catastrophizing) to 52 (greatest level of catastrophizing). The Pain Self-Efficacy Questionnaire was used to measure the degree to which patients mitigate pain and the negative emotions associated with it to maintain everyday life activities, including work.9 Total scores on this questionnaire range from 0 (no self-efficacy) to 60 (greatest level of self-efficacy).
Low back pain was measured with an 11-point numerical rating scale (NRS) that assessed average pain over the past seven days, ranging from 0 (no pain) to 10 (worst possible pain). Back-related functioning was measured with the Roland-Morris Disability Questionnaire (RMDQ),10 consisting of 24 items that are scored as either 1 (low back pain has an adverse impact on functioning) or 0 (low back pain does not have an adverse impact). The RMDQ is scored as the sum of responses to each item, thereby potentially ranging from 0 to 24. Quality of life was measured with the Patient-Reported Outcomes Measurement Information System (PROMIS).11 The seven scales that comprise the PROMIS-29 include physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain interference with activities. Crude survey responses were transformed and standardized using scoring algorithms such that 50 and 10 represent the mean and standard deviation, respectively, on each scale. The SPADE cluster (sleep disturbance, pain interference, anxiety, depression, and low energy/fatigue) was then derived as a composite measure of quality of life from the PROMIS-29 by computing the mean of its five component scales.12 The SPADE cluster represents co-occurring symptoms that have a greater adverse impact on quality of life in patients with chronic pain than do isolated symptoms.
Descriptive statistics were computed and reported using the number and percentage for categorical variables, and the mean and standard deviation (SD) for continuous variables. The three measures used to assess the clinical status of patients upon enrolling in the registry were the NRS for low back pain intensity, RMDQ for back-related functioning, and SPADE cluster for quality of life. Low back pain intensity was classified as mild (0-3), moderate (4-6), or severe (7-10) based on NRS scores. The RMDQ scores were classified as representing low (0-13) or high (14-24) levels of back-related disability based on a median split of scores from the entire registry population. The SPADE cluster scores were classified as representing good (<55) or poor (≥55) quality of life. The latter represent scores that are at least 0.5 SD worse than the mean for the general population.
Multiple logistic regression was used to compute odds ratios (ORs) and 95 percent confidence intervals (CIs) for the use of opioids and NSAIDs, controlling for patient demographic and clinical characteristics. The mean and 95 percent CIs for clinical status measures were computed for the groups of patients who were using opioids, NSAIDs, both opioids and NSAIDs concurrently, and no or other drugs for low back pain upon enrollment in the registry. These group statistics were compared using analysis of variance with Bonferroni post-hoc tests. Multiple logistic regression models were also used to compute ORs and 95 percent CIs for adverse clinical status pertaining to low back pain intensity, back-related functioning, and quality of life at the time of registry enrollment, controlling for potential confounders including age, gender, cigarette smoking, low back pain duration and frequency, pain catastrophizing, and pain self-efficacy. Pain intensity was dichotomized as severe (NRS score≥7) versus mild or moderate (NRS score<7) in these models. Pharmacologic therapy was classified as opioids, NSAIDs, or both opioids and NSAIDs, with no or other drugs as the referent category. Patient-reported data were exported from Qualtrics to the IBM SPSS Statistics software (version 23) for analysis. Hypotheses were assessed at the .05 level of statistical significance with two-sided testing.
The case definition for chronic low back pain was met by 202 (85.6 percent) registry patients who comprised the study population. Their mean age was 54.2 years (SD, 11.1 years), and 126 (62.4 percent) were women. The other sociodemographic characteristics of patients are summarized in Table 1.
A total of 130 (64.4 percent) patients experienced low back pain for more than five years, and 121 (59.9 percent) patients reported pain every day or nearly every day over the past six months. Patients were most commonly diagnosed with the spine-related conditions of herniated disc and sciatica, and with the medical conditions of depression and hypertension. The reported current or previous use of nonpharmacologic treatments for chronic low back pain includes: exercise, yoga, spinal manipulative therapy, acupuncture, and cognitive behavioral therapy. Fifty-three (26.2 percent) patients had never used any of these five nonpharmacologic treatments. The use of nonpharmacologic treatments among patients who were using opioids was similar to the overall utilization rates. Sixty-five (32.2 percent) patients were currently using opioids, and 130 (64.4%) patients were using NSAIDs. Thirty-three (16.3 percent) patients were concurrently using both opioids and NSAIDs. Other clinical characteristics of patients are summarized in Table 2. The mean NRS score for low back pain intensity was 6.2 (SD, 2.0). There were 17 (8.4 percent) patients with mild pain, 99 (49.0 percent) with moderate pain, and 86 (42.6 percent) with severe pain.
The mean RMDQ score was 13.5 (SD, 6.2). The mean PCS and PSEQ scores were 17.9 (SD, 14.2) and 35.7 (SD, 15.6), respectively. The results of the multiple logistic regression models for use of opioids and NSAIDs upon registry enrollment are presented in Table 3. Patients 50-59 years old and 60-79 years old were more likely to be using opioids in comparison with younger patients. No other factor was significantly associated with the use of either opioids or NSAIDs in these multivariate models.
Clinical status measures according to current pharmacologic therapy at the time of enrollment are presented in Table 4. Patients using opioids reported greater intensity of low back pain and greater back-related disability than patients using NSAIDs. Patients concurrently using both opioids and NSAIDs reported greater back-related disability, and poorer quality of life than patients using no or other pharmacologic therapy. Concurrent opioid and NSAID use was also associated with higher pain catastrophizing, and lower pain self-efficacy, relative to use of no or other pharmacologic therapy.
The results of the multiple logistic regression models that further assessed the effect of pharmacologic therapy on low back pain intensity, back-related functioning, and quality of life, while controlling for potential confounders, are presented in Table 5. None of the pharmacologic therapy regimens was significantly associated with any of the three clinical status measures in these models.
This study included patients who typically had low back pain for several years and experienced pain every day or nearly every day. Thus, the treatments reported herein likely represent their established pharmacologic therapy. About one-third of patients were using opioids, and two-thirds were using NSAIDs for low back pain. About one-half of the opioid users were simultaneously using NSAIDs. Thus, it appears that most patients may have received pharmacologic therapy for low back pain that aligned with the CDC guideline on prescribing analgesics for chronic pain2 and with the current recommendations of the American College of Physicians,4 which do not advocate considering opioids unless patients have failed to adequately respond to first-line pharmacologic therapies. Nevertheless, opioid use (including in combination with NSAIDs) did not result in less pain, better functioning, or better quality of life than simply using NSAIDs. In fact, patients taking NSAIDs (without opioids) reported significantly less pain and better functioning than patients taking opioids (without NSAIDs), although these associations were no longer observed after controlling for potential confounders.
Note that trials of common nonpharmacologic treatments were not universally undertaken by patients with chronic low back pain, even before progressing to opioid use. Only exercise was used by a majority of patients, and over one-fourth of patients reported not using any of the five nonpharmacologic treatments studied, including in the subgroup of patients who were taking opioids. When extrapolated to the general population, these findings suggest that a substantial number of patients with chronic low back pain may not adequately explore nonpharmacologic treatment options. The biopsychosocial model maintains that the biological and psychosocial factors that are related to chronic pain may guide an interdisciplinary treatment approach.13 Pain catastrophizing and pain self-efficacy are psychosocial factors that have received much attention in connection with chronic low back pain. Research suggests that catastrophizing is a dysfunctional coping strategy in patients with low back pain,14 and that higher self-efficacy is associated with positive findings in patients with chronic musculoskeletal pain.15 Thus, cognitive behavioral therapy appears to be a particularly underutilized nonpharmacologic intervention given the high prevalence of depression reported by patients and the significant associations of high pain catastrophizing and low pain self-efficacy with opioid use in this study. Also, increasing age was the strongest factor associated with using opioids, with the odds of opioid use more than three-fold greater among patients in the 60-79 year-old category compared with younger referents. Before progressing to opioid use, cognitive behavioral therapy or other pain self-management techniques may represent attractive options for older patients who are not suitable candidates for other nonpharmacologic treatments.
The findings of this study indicate that patients using opioids for chronic low back pain, including opioids in combination with NSAIDs, did not report better pain, functioning, or quality of life measures than did patients using NSAIDs. This brings into question the effectiveness of opioid therapy for chronic low back pain, and highlights the need for more research on second-line pharmacologic therapies, including combination therapies. A recent trial comparing single doses of opioid and nonopioid combination therapies for acute extremity pain in the emergency department found comparable pain reduction with combined ibuprofen and acetaminophen when compared with other opioid and acetaminophen combinations.16 More research involving NSAID and acetaminophen combinations for chronic low back pain appears warranted as these drugs are widely available without prescription, have different mechanisms of action, and may provide additive analgesic effects with lower risk of adverse events than opioid-containing combinations.17
The use of a community-based registry facilitated inclusion of patients with chronic low back pain who were representative of the general population. However, research within a registry has limitations that should be noted. Patients may take multiple drugs to control their low back pain because many pharmacologic therapies are available for pain, including nonprescription drugs. Thus, some patients using opioids, NSAIDs, or both may also have been taking other drugs. This observational study was limited in that it was not feasible to restrict, or even to classify, all possible drug combinations used by patients, and thereby not feasible to exclusively study monotherapy or combined therapy involving only opioids and NSAIDs. Also, although many findings were clinically relevant and statistically significant (Table 4), statistical power was more limited in the multivariate analyses. Several factors showed only a trend toward significance (Table 3). The latter may represent type 2 errors because of insufficient sample size. Nevertheless, the magnitude of the ORs in the multivariate analyses for low back pain and functioning (Table 5) would likely be of only marginal clinical relevance, even if statistical significance had been achieved with a greater sample size.
In summary, opioids and opioids combined with NSAIDs were not more effective than NSAIDs alone with respect to pain intensity, back-related functioning, and quality of life. Greater use of nonpharmacologic therapies and better second-line, nonopioid pharmacologic therapies appear necessary for more effective treatment of chronic low back pain.
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Tex Med. 2018;114(10):e1
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