The Cox regression with prescription opioid dose categorized into low, medium, and high revealed that participants receiving a medium dose vs a low dose did not have a significantly increased crude hazard ratio of past-year heroin use. In the fully adjusted model, high dose compared to low dose was positively and significantly associated with past-year heroin use (AHR = 3.16, 95% CI = 1.75-5.68).
The stabilized inverse probability of exposure weights was statistically well behaved for both primary exposures of interest. The mean of the weights for receipt of high-dose prescription opioids was 0.99 (SD = 0.23) and they ranged from 0.25 to 4.51. The mean of the weights for receipt of a long-term prescription opioid was 1.00 (SD = 0.30) and they ranged from 0.18 to 3.61. In the sensitivity analysis with treatment and censoring weights, participants who received high-dose prescription opioids from the VA had 2.11 the hazard of past-year heroin use compared to participants who received prescription opioids in doses less than 90 mg MEDD (95% CI: 1.30-3.43). The receipt of LTOT from the VA was not significantly associated with past-year heroin use in the sensitivity analysis.
In this study, we examined the relationship between specific opioid-prescribing patterns and subsequent heroin use in a population of US military veterans receiving medical care in the VA system. Our results indicate that among veterans who reported no past-year illicit opioid use at baseline and who received prescription opioids from the VA, prior receipt of high-dose prescription opioids increased the risk of subsequent heroin use over follow-up.
Our findings suggest that diagnosis and treatment of psychiatric disorders are important considerations when prescribing opioid therapy, although existing guidelines concerning the use of opioids vary widely in their recommendations regarding patients with comorbid depression and other psychiatric disorders.52 Lower household wealth is associated with chronic pain that substantially limits participation in daily activities.28 Therefore, the fact that work-related pain interference in daily life remained associated with an increased risk of past-year heroin use in the fully adjusted model suggests that patients may be engaging in heroin use to alleviate pain that has not been adequately addressed by prescription opioid therapy and that efforts to reduce the burden of disabling chronic pain should prioritize socioeconomically vulnerable groups.
More than half of VA primary care patients report pain, with many reporting chronic pain; however, current VA/Department of Defense opioid therapy guidelines recommend use of long-acting opioids only for persistent pain, and prescription of opioid therapy for chronic pain only after other nonopioid analgesic pharmacotherapies and nonpharmacological pain treatments have insufficiently improved pain-related function.37 Although our results further substantiate current VA and CDC opioid-prescribing guidelines, which recommended prescribing opioids for short durations and recommend against prescribing opioids in doses greater than 90 mg MEDD,55 Gaither et al.22 found that from 1998 to 2010, the majority of VA patients initiating LTOT did not receive opioid therapy guideline-concordant care (although older guidelines were in effect when this study was published). Future research is needed to determine the extent to which opioid prescribing is consistent with current guidelines.
We posit that prior receipt of long-term opioid prescriptions was not associated with past-year heroin use because our data were collected before the enactment of recent CDC and VA/DOD guidelines regarding the tapering of high-dose prescription opioids, and it is unlikely that opioid tapering and/or abrupt discontinuation of opioid therapy drove patients to engage in heroin use during this period.16 Nonetheless, future studies should examine whether abrupt discontinuation or inappropriate tapering of opioid therapy is associated with an increased risk of transitioning to heroin use among veterans and high-risk populations. This is particularly important in the context of the VA's Opioid Safety Initiative, which strongly encourages opioid tapering, if not discontinuation, without explicit examination of unintended harms of this initiative.59 It is essential to continue addressing unmet pain management needs of veterans, as is also recommended by guidelines from the American College of Physicians, which specifically recommends increased use of nonopioid pharmacological and nonpharmacological approaches.9
Our study has a number of limitations. First, there is a potential for confounding by indication, whereby patients at higher risk of heroin use were also more likely to receive high-dose prescription opioids. We addressed this by using inverse probability weighting methods, and creating weights based on patients' probability of receiving high-dose opioids, conditioned on a comprehensive list of potential, time-updated confounders.58 Second, our exposure data were based on pharmacy fill/refill records from the VA, and we were not able to account for opioid prescriptions filled outside of the VA.23,24 One recent study demonstrated that 18% of veterans receive opioids both inside and outside of the VA.4 In that vein, receipt of a prescription opioid prescription may not have accurately captured the true amount of opioids actually being taken by VACS participants. There is also some likelihood of measurement error and bias in our outcome variable: past-year heroin use. Although this variable captures self-report of any heroin use in the 10-year follow-up period, we were not able to discern whether this is truly lifetime incident heroin use or represents reinitiation of heroin use. We only used a single domain (eg, work-related interference) to measure pain interference in daily life. The complexity of chronic pain and its interference in daily activities is likely not fully captured by this question. In addition, almost 50% of participants reported being retired or unable to work at baseline, which may have affected the validity and measurement of this item. Moreover, because we did not measure employment status over time, we are unable to examine whether daily pain interfered in employment status, or loss of employment related to chronic pain increased the risk of heroin use. Despite these limitations, our study has important implications for clinical care, policy, and future research. The finding that prior receipt of a high-dose prescription opioid may increase the risk of past-year heroin use among veterans receiving care at the VA supports the current CDC and VA guidelines that recommend prescribing opioid at lower doses. Our results indicate that further efforts are needed to develop effective screening strategies to identify heroin use among those prescribed with high-dose opioids.
The authors have no conflict of interest to declare.
This work was funded by a NIDA NIH Dissertation Grant, R36DA042877, as well as NIH grants U01 AA020790, U24 AA020794, and RO1 DA040471. BDLM is supported by NIH grant P20-GM125507.
Supplemental audio content
Audio accompanying this abstract is available online as supplemental digital content at http://links.lww.com/PAIN/A812.
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