High-dose opioid therapy was prescribed for 2–3% of veterans with chronic non-cancer pain who were prescribed opioids long-term. Patients in the high-dose opioid group were prescribed an average daily opioid dose of 325 mg per day morphine equivalent, a dose 10 times greater than that of patients in the traditional-dose opioid group. High-dose patients had pain intensity scores similar to patients in the traditional-dose group and significantly higher than patients in the no opioid group. Specific reasons why patients in the high-dose group had the highest pain intensity scores were not identified, but may be due to greater medical morbidity, increased tolerance to opioids, central sensitization, or to other factors not assessed (e.g., severity of illness).
In this study, certain demographic and clinical factors were associated with high-dose opioid use. Black patients were less likely to be in the high-dose group, a finding which is consistent with prior research indicating patients who are black receive fewer services for the treatment of chronic pain [36
] and find pain treatment less effective [20
]. Patients in the high-dose group were more likely to be diagnosed with four or more pain diagnoses, as well as a variety of medical, psychiatric, and substance use disorder diagnoses. These results are consistent with prior studies indicating that patients with chronic pain and comorbid psychiatric disorders are more likely to receive opioids than pain patients without comorbid psychopathology [7
], and extend prior literature by showing that these diagnoses are also associated with prescription of high opioid doses.
Results from the regression analysis identified several factors associated with being in the high-dose group relative to patients in the traditional-dose group. Significant results were found for certain pain diagnoses (neuropathy, low back pain) and nicotine dependence, which increased the likelihood of being prescribed high-doses of opioids. Contrary to our initial hypotheses, there were no statistically robust predictors of high-dose opioid use, as the significant odds ratios were all less than 2.0. The finding that a diagnosis of nicotine dependence was associated with an increased likelihood of receiving high doses of opioids is consistent with recent research which found that nicotine use predicted long-term opioid use among patients with painful spine conditions [29
]. We also found that a diagnosis of hypertension was associated with a decreased likelihood of being in the high-dose group. While hypertension may be a marker for some other illness or treatment factor, previous literature has also documented a relationship between hypertension and pain sensitivity, showing a negative correlation between blood pressure and pain regulation [1
Prior research indicates that opioid prescribing varies considerably by provider and that several factors inhibit prescription of opioid medications, including perceived regulatory scrutiny, knowledge gaps, concern about risk of dependence or addiction, and negative views about patients with chronic pain [39
]. In a recent study of VA primary care providers, a large degree of variation in rates of prescribing opioids was associated with clinician panel size, job and resource satisfaction, and professional training [19
]. Future research might also evaluate the relationship between opioid prescriber and opioid dose. In our study, we adjusted for practice variation using VA facility, though this variable was not significantly associated with prevalence of high-dose opioid prescriptions.
Guidelines have been published which provide recommendations for managing patients prescribed opioids for chronic non-cancer pain [2
]. Although the primary purpose of the present study was not to evaluate the extent to which patients prescribed high doses of opioids received guideline-concordant care, some of our findings address these issues. Consistent with recommended guidelines was the small proportion of patients taking two or more short-acting opioids, which did not differ by group status (9.0% in the high-dose group versus 12.2% in traditional-dose group). Patients in the high-dose group were most likely to be prescribed a long-acting opioid; 96.9% in high-dose group versus 22.6% in the traditional-dose group. Patients in the high-dose group were more likely to be prescribed the combination of only one long-acting opioid and no short-acting opioids (23.2% versus 7.6%). Treatment recommendations generally support the use of long-acting opioids for chronic pain, though it has been suggested that this pattern of prescribing could also contribute to tolerance and possibly dose escalation [5
Patients in the high-dose opioid group had the highest rates of alcohol or substance use disorders (36.6%). Although individuals with a substance use disorder should not necessarily be denied access to opioid therapy, this group is at greater risk for misuse of prescription medications and should receive more intensive structure and monitoring [13
]. The overall rate of past-year administrations of urine drug screens was low, 39.9% in the entire sample, which did not differ by group status. Seventy-five percent of patients in the high-dose group were prescribed at least one short-acting opioid, and 9.4% were concurrently prescribed two or more short-acting opioids, rates which are higher than guideline-recommended care. Patients in the high-dose group had the highest rate of benzodiazepine prescriptions (32.0% versus 25.2% in traditional-dose group and 9.6% in no opioid group). The frequent use of short-acting opioids, high rates of sedative-hypnotic (benzodiazepine) prescribing, and relatively low rates of urine drug screen monitoring suggests that patients prescribed high doses of opioids may be at greater risk of not receiving guideline-level chronic pain care [13
]. Other settings have identified a similar pattern of care among patients prescribed opioids for low back pain [17
], suggesting these results are not unique to a specific geographical area or health system. More explicit opioid treatment guidelines regarding high-dose opioid use may be needed, as well as better system support to assist providers.
There are several limitations that are important to consider when reviewing the results from this study. Due to our research methodology, we were unable to identify reasons why these patients were prescribed high-dose opioid therapy or the effectiveness of treatment. Future studies using similar datasets may be able to assess the effectiveness of opioid therapy by tracking opioid dose and pain intensity (or pain-related function) scores over time. All data for this study were obtained from electronic medical records as part of standard clinical care. Medical and psychiatric diagnoses were not confirmed with laboratory data or via structured clinical interviews. Further, diagnoses were obtained over the past five years, and some disorders may have not been problematic at the time opioid use was assessed. This methodology provides a comprehensive assessment of medical comorbidity, but may not fully assess severity, which could be a better predictor of opioid dose. Participants included were veterans receiving medical care in the Pacific Northwest portion of the United States and results may not be generalizable to non-veterans or to veterans seeking care elsewhere. In addition, consistent with a general VA population, the majority of participants in our study were male, though chronic pain may be more common among women, and research suggests women may have different responses to opioid analgesia than men [23
], further limiting the generalizability of our results. Our definition of chronic non-cancer pain was dependent upon having pain numeric rating scores ≥ 4 documented in the medical record in three separate months in 2008. This methodology is consistent with some prior research [25
], but may skew our sample toward a cohort that utilizes medical services at a high rate and to patients with a moderate to high degree of pain. Finally, we limited our examination to dose of opioid medication and did not assess other potentially relevant aspects of opioid exposure (e.g., duration).
Opioid medications are widely used in the management of chronic pain. Findings from this study indicate that two to three percent of patients with moderate to severe chronic non-cancer pain are prescribed high doses of opioids on a long-term basis and that certain clinical factors are associated with high-dose opioid use. Patients receiving high doses of opioids may not be receiving some aspects of guideline recommended care in that patients frequently receive short-acting opioids, there are high rates of sedative-hypnotic use, and relatively low rates of urine drug screen monitoring [13
]. Additional empirical data are needed to replicate these findings, explore alternative factors that result in patients being prescribed high doses of opioids, and to assess the utility and safety of taking high doses of opioids.