Research on Risks, Effectiveness of Long-Term Opioid Pain Therapy Given a Failing Grade

Roger Rabb, J.D., Special Correspondent for the LexisNexis Workers’ Compensation eNewsletter

As physicians continue to prescribe opioids such as Vicodin, OxyContin, and codeine to help patients with chronic pain, there is a growing concern that the costs of such pain treatment options, whether in the form of addiction or abuse or other detrimental side effects, seriously outweigh the perceived benefits. A recent review of the research literature on the risks and effectiveness of long-term opioid use for pain treatment published in the Annals of Internal Medicine, “The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop,” adds more fuel to this particular fire, concluding that the existing research is woefully inadequate, especially in light of mounting evidence of the harms associated with that use.As noted by the authors of that review, prescriptions of opioids for chronic pain lasting longer than three months have increased dramatically. However, although evidence may support the conclusion that short-term opioid therapy can alleviate pain in injured patients, the authors note that most opioid trials are six weeks or less and are of limited value in evaluating the long-term effectiveness and harms associated with this course of treatment, with “long-term” defined as a period greater than one year.

In evaluating the existing research, the authors looked for evidence relating to five specific issues involving long-term opioid therapy:

> Effectiveness of long-term opioid therapy (for long-term outcomes relating to pain, function, and quality of life) compared to the use of placebo, no opioid therapy, or nonopioid therapy. The authors discovered that there were no studies meeting their inclusion criteria that addressed this issue, finding that most placebo-controlled studies were shorter than six weeks.

> Risks of opioid use (i.e., opioid abuse, addiction, overdoses, falls, fractures, motor vehicle accidents, endocrinological harms, and cardiovascular events) compared to placebo or no opioid use. The authors noted that several controlled studies supported the conclusion that, compared with no opioid use, opioid therapy for chronic pain was associated with increased risk for overdose, opioid abuse and dependency, fractures, myocardial infarction, and use of medications to treat sexual dysfunction, and that higher opioid doses were associated with increased risks. The authors also found support in uncontrolled studies for increased risks of drug abuse and dependency, although the drug abuse rates and related outcomes varied substantially among these studies.

> Comparative effectiveness of opioid dosing strategies (e.g., opioid selection, dose initiation and titration, and dose escalation versus maintenance) on pain, function, quality of life, and risk for overdose, addiction, abuse, or misuse. The authors found a limited amount of evidence on the effectiveness of different opioid dosing strategies. They concluded that the “[e]vidence on benefits and harms of methods for initiating opioid therapy and titrating doses, use of short- versus long-acting opioids, scheduled and continuous versus as-needed dosing, use of opioid rotation, and methods for tapering doses or discontinuing long-term therapy was insufficient to reach reliable conclusions.” The authors also noted limited evidence supporting the conclusion that allowing patients to have doses titrated for adequate pain control showed no clear differences in the effectiveness of different long-acting opioids.

> Accuracy of risk assessment, i.e., predicting risk for opioid overdose, addiction, abuse, or misuse before opioid therapy is initiated. The authors could make no reliable conclusions on this topic, finding “sparse” evidence “characterized by methodological limitations and inconsistent findings.”

> Effectiveness of risk mitigation strategies (e.g., patient education, urine drug screening, and prescription drug monitoring programs) on outcomes related to overdose, addiction, abuse, or misuse. The authors also found no studies related to this topic that met their inclusion criteria, although they noted that a previous review, relying on studies that they would not include, found some association between opioid management plans and urine drug screening and a decreased risk of “misuse behaviors.”

The authors noted certain limits to their review. For example, they included only English-language articles and excluded studies published only as abstracts. They performed no “meta-analysis” and could not assess for publication bias. While they also recognized that studies evaluating periods of opioid use of less than one year might prove useful when evaluating long-term opioid use, they found no placebo-controlled trials that lasted at least six months. They also noted that some potentially relevant studies had been excluded because they could not ascertain whether the patients had chronic pain or received long-term opioid therapy.

Given the paucity of adequate research on these topics, making reliable conclusions as to the effectiveness of long-term opioid therapy impossible, the authors called for more, better research on the long-term risks and rewards of opioid pain therapy. In summing up the current state of the research, they state simply that “the lack of scientific evidence on effectiveness and harms of long-term opioid therapy for chronic pain is clear and is in striking contrast to its widespread use for this condition and the large increase in prescription opioid-related overdoses.” It remains to be seen whether future research will support the use of opioids as a long-term pain treatment strategy, despite the obvious risks that accompany that treatment path, or whether new research will provide the impetus to curb this potentially dangerous practice.

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