Wednesday, November 21, 2012

Pain, Depression, Anxiety in Rx-Opioid Misusers

Briefly NotedNonmedical prescription opioid use has become a substantial public health concern in North America and most other countries. Limited epidemiological data suggest an association between such Rx-opioid misuse and mental health or pain symptoms in different populations, although these correlations have not been systematically assessed, which was the purpose of a new study.

A team of Canadian researchers conducted a thorough systematic search, review, and meta-analysis to examine mental health problem symptoms and pain in general population samples reporting nonmedical Rx-opioid use [Fischer et al. 2012]. Overall, 9 qualifying epidemiological studies were identified and included in the review; 5 contributed data on the prevalence of mental health issues and 4 had data on the prevalence of pain in the target population. Most studies (8) were based on populations in the United States and the other one was centered in Ontario, Canada.

Writing in the November 2012 edition of the Journal of Pain, the researchers report that the pooled prevalence of any mental health symptoms in general population samples reporting nonmedical Rx-opioid use was 32% (95% confidence interval [CI], 24–40). Specifically, the pooled prevalence of depression was 17% (95% CI, 14–19) and the prevalence of anxiety was 16% (95% CI, 1–30). The pooled prevalence of pain in the population of interest was found to be 48% (95% CI, 37–59).

The researchers conclude that their study found evidence for disproportionately high prevalence levels of mental health problems (anxiety and depression) and pain among nonmedical Rx-opioid users in the general population. While causality cannot be established by such data, these comorbidities may influence Rx-opioid misuse and should be considered in preventive and treatment interventions.

COMMENTARY: Curiously, Fischer and colleagues do not even mention in their report the prevalence of nonmedical Rx-opioid use found in the 9 epidemiological studies they examined. However, they do include raw data in a table of study characteristics and extrapolating from those data we calculated the prevalence of Rx-opioid misuse as ranging from 1.8% to 12% (mean 5.6%; 95% CI, 3-8.2).

Judging whether 5.6% on average is an extraordinarily high and intolerable prevalence of Rx-opioid misuse requires further consideration of all factors that might be contributing to or account for the alleged aberrant behaviors. However, the wide prevalence range alone suggests that either the measurement of Rx-opioid misuse across studies was inconsistent or the populations examined were significantly different from each other.

The researchers defined “nonmedical use” or “misuse” as the use of Rx-opioids without being medically sanctioned, which may include, but is not limited to, the consumption of these medications for purposes other than prescribed, or taking nonprescribed, diverted, or illicitly obtained Rx-opioids. However, considering the high prevalence of pain, one must question how much of the putative “nonmedical use” actually was for medical purposes (pain relief), which raises questions about access to healthcare and/or the undertreatment of pain via legitimate healthcare channels.

Prevalence levels of anxiety and depression also were considered to be quite high by the researchers, but it is not known if these factors influenced Rx-opioid misuse, if they resulted from such misbehavior, or if they were largely related to unrelieved pain. These are important concerns worthy of further investigation.

Most, but not all, of the included epidemiological studies were of significant size; however, since all of them were focused in North America (primarily the U.S.), the results cannot be generalized to other populations. It is somewhat surprising that these issues have not been investigated by large-scale epidemiological surveys in the general populations of other countries.

There were some critical limitations of this review and meta-analysis by Fischer et al. that are noteworthy and question its validity. Concepts of systematic reviews and meta-analyses were discussed in a recent UPDATE here, and here are some of the concerns in the present study:

  • There was a significantly high degree of heterogeneity across all of the studies included in meta-analyses, even though differences between many of the studies were small and their confidence intervals were very narrow. For the 4 major analyses — any mental health symptoms, depression, anxiety, and pain — I² values (suggesting the amount of heterogeneity) were 97.3%, 94.8%, 99.8%, and 95.5%, respectively.

  • Also, there were extremely few studies for each of the 4 meta-analyses regarding factors of interest: 3 studies for any mental health symptoms, 2 each for depression and anxiety, and 4 for pain.

  • Appropriately, the researchers used random-effects modeling in the pooling of data; however, with so few studies they could not do any sensitivity analyses to determine sources of bias and reliability of results.

In sum, there were so many fundamental differences between studies — eg, population composition, definitions, assessment measures, etc. — influencing heterogeneity, and so few studies for each analysis, that it is questionable whether conducting meta-analyses of the data was appropriate. Perhaps, there have been other studies on these issues that were undiscovered by the researchers’ systematic review, although it did seem to be quite thorough. In any case, there is clearly a need for additional and more consistent research before reliable and valid conclusions can be reached on this subject of factors associated with nonmedical Rx-opioid use.

REFERENCE: Fischer B, Lusted A, Roerecke M, et al. The Prevalence of Mental Health and Pain Symptoms in General Population Samples Reporting Nonmedical Use of Prescription Opioids: A Systematic Review and Meta-Analysis. J Pain. 2012(Nov);13(11):1029-1044 [abstract here].

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