To our knowledge, this is the largest study to date of risk factors for opioid abuse/dependence and non-opioid substance abuse/dependence among COT users. The sample is sociodemographically diverse, and we utilized five years of “real world” data from health care plans covering multiple states and regions of the country. For these reasons we believe our results enjoy good generalizability.
In a sample with at least 90 days of continuous opioid use, we found that opioid abuse/dependence was diagnosed in 3.2% and 2.9% of HealthCore and Arkansas Medicaid enrollees respectively. These rates are consistent with a study that used VA administrative data (Edlund et al., 2007a
), but substantially higher than the 1.3% found in a study that used administrative data from Missouri (Cicero et al., 2009
). However, the Missouri study only utilized one year of data, while the VA study and our current study utilized several years of data to increase sensitivity, as suggested by measurement experts (O’Malley et al., 2005
). Our estimates of the prevalence of opioid abuse/dependence are compatible with estimates of “problem opioid use,” 3.5%, derived from interviews in the nationally-representative Healthcare for Communities (HCC) household survey.
Both administrative and survey data may under-estimate actual rates of opioid abuse/dependence, and thus our estimates should be viewed as lower bounds. Regarding administrative data, under-detection of substance use disorders by clinicians, and indeed all kinds of disorders, is common (Borowsky et al., 2000
; Cleary and McNeil, 1988
; Lefevre et al., 1999
; Spitzer et al., 1999
; Wells et al., 1989
); in household surveys, individuals may minimize their level of drug use, due to social-undesirability. Further, there is likely significant opioid misuse that does not rise to the level of DSM-IV abuse or dependence.
The rates of post-index non-opioid substance abuse/dependence, 4.4% in the HealthCore sample and 13.8% in the Arkansas Medicaid sample, were higher than rates of post-index opioid abuse/dependence. This suggests that clinicians must be vigilant for both opioid and non-opioid substance abuse disorders (e.g., alcohol abuse or dependence, or methamphetamine abuse or dependence) in COT patients. It is interesting that the predictors of post-index opioid abuse/dependence and post-index non-opioid substance abuse/dependence were similar, and several factors may be involved. The most worrisome possibility is that many individuals receiving COT may have a predisposition for substance abuse. On the other hand, it could be that clinicians are just more vigilant in detecting these disorders among individuals on COT.
The factors associated with a higher or lower likelihood of opioid abuse/dependence among those receiving COT were similar across our two disparate samples. Among non-modifiable risk factors, younger individuals had substantially higher rates of post-index opioid abuse/dependence. Age effects were strong; for example, the ORs for those ages 31 to 40 were 4.16 and 11.39 for HealthCore and Arkansas Medicaid respectively, compared to the reference group of individuals 65 or older. These results are consistent with substance abuse patterns in general, which show higher rates in younger individuals (Compton et al., 2007
; Grant et al., 2004a
; Swendsen et al., 2009
). The age results deserve emphasis, because COT patients are often young (23% of the HealthCore COT sample was age 40 or younger, and 23% of the Medicaid COT sample); age is highly protective from abuse of opioid abuse/dependence; and age can be assessed quickly and reliably. By way of comparison, the OR’s for age were larger than the OR’s for pre-index opioid abuse/dependence and pre-index non-opioid substance abuse/dependence, well recognized risk factors for opioid abuse/dependence. Given this, we believe that guidelines should emphasize that age, particularly younger age, is a risk factor for opioid abuse and dependence, and standardized questionnaires developed for predicting aberrant opioid use in CNCP patients should include age.
The American Geriatrics Society recommends that opioids generally be used in geriatric populations before NSAIDs and Cox-II inhibitors (acetaminophen is recommended as first line agent) (American Geriatrics Society, 2009
). While use of COT is a complex decision involving many factors, the protective effect of older age demonstrated in our data lends support to these recommendations. On the other hand, our results suggest that clinicians must be especially cautious in balancing the risks and benefits of COT in younger individuals.
Mental disorders can be difficult to successfully treat in patients with chronic pain (Bair et al., 2003
; Thielke et al., 2007
) and thus the extent to which mental health disorders are potentially modifiable in patients with CNCP is debatable. However, their importance as risk factors for opioid abuse/dependence is undeniable (Edlund et al., 2007a
; Martins et al., 2009
). In other studies (Cicero et al., 2009
; Edlund et al., 2007a
) and the present study mental health disorders are extremely common among patients receiving COT; 18% of the HealthCore sample had one or more mental health diagnosis, and 32% of the Arkansas Medicaid had one or more mental health diagnosis, and these estimates are likely conservative, due to well-documented under-diagnosis in primary care clinical practice. The magnitude of their effects were moderate, with OR’s in HealthCore of 1.73 (1 mental health disorder vs no disorder) to 2.08 (2 mental health disorders vs no disorders). To the extent that mental health disorders can be successfully treated, such treatment might decrease the risk of development of opioid abuse/dependence in COT users. Thus, we believe our work highlights the importance of assessment and treatment of mental health disorders in patients receiving or being considered for COT.
Specific tracer chronic pain types were statistically associated with the likelihood of opioid abuse/dependence, although the effects were modest; statistically significant results with only modest size coefficients are not unusual with large sample. Because the magnitudes of the effects were relatively modest, we do not believe that clinicians should base decisions about COT solely on pain location.
The Washington State Opioid Dosing Guidelines has specified greater than 120 mg of morphine equivalents as “high dose” opioid therapy, which may require specialty consultation or closer monitoring. Our results generally supported this. Individuals on greater than 120 mg morphine equivalents did have significantly increased diagnoses of post-index opioid abuse/dependence. However, they also had significantly higher diagnoses of post-index non-opioid substance abuse/dependence. Thus there are multiple explanations for our findings, none of which are mutually exclusive: individuals with a predisposition for substance abuse may seek higher opioid doses from their clinicians; higher opioid doses may lead to both higher opioid abuse and non-opioid substance abuse; or clinicians may be more ready to diagnose substance use disorders with their patients treated with high doses of opioids. Likely all factors contribute to our results. In any event, those on opioid daily doses of greater than 120 mg do seem to comprise a high-risk group for substance abuse. The opioids days supply was also associated with the likelihood of post-index opioid abuse/dependence and post-index non-opioid abuse/dependence in HealthCore (but not in Arkansas Medicaid). This suggests that individuals with daily rather than intermittent use (e.g., 160-185 days group) and individuals using multiple opioid types (e.g., 185+ days group) may be at increased risk for abuse. The relationship between opioids day supply and post-index abuse/dependence is also likely complex and bi-directional. That is, daily use is likely a causal risk factor for opioid abuse/dependence, and patients with opioid abuse/dependence may be more likely to aggressively seek daily prescription opioids from their clinicians.
While we hypothesized that long acting Schedule II opioids would have the weakest association with opioid abuse/dependence, in HealthCore all opioid type categories that included Schedule-II long-acting opioids had a higher likelihood of post-index abuse/dependence. Some of the increased risk seen with long-acting opioids may be due to methadone prescribed for pain to high-risk individuals, although overall use of methadone was relatively infrequent in both HealthCore and Arkansas Medicaid. Individuals who used only Schedule III or IV opioids had lower rates of post-index opioid abuse/dependence than individuals in the opioid type categories that included Schedule II opioids, although these differences were not always significant. Schedule-II long-acting opioids are the focus of the FDA’s Risk Evaluation and Mitigation Strategy. However, in both samples of COT users the large majority of individuals had Schedule III or IV opioid use only, and about half of the individuals with post-index opioid abuse/dependence had Schedule III or IV use only. This suggests policy changes aimed at decreasing the incidence and prevalence of opioid abuse/dependence need to be directed at not only Schedule II opioids, but also Schedule III and Schedule IV opioids.