Wednesday, February 3, 2010

Opioids Relieve Pain with Little Addiction Risk

According to a comprehensive updated Cochrane review, opioid analgesics effectively relieve chronic noncancer pain in most patients, with only a small (though not zero) risk of developing abuse or addiction. However, it must be appreciated that a portion of patients may have inadequate pain relief or develop intolerable opioid side effects; further research is needed to identify patients who will benefit the most.

Many still consider opioid therapy for chronic noncancer pain (CNCP) as controversial due to concerns about long-term effectiveness and safety, particularly risks of tolerance, dependence, or abuse. To expand and update an earlier Cochrane Review on this subject, investigators searched 10 bibliographic databases up to May 2009 [Noble et al. 2010]. They discovered for review 26 studies with 27 treatment groups that enrolled a total of 4,893 participants taking opioids for as long as 48 months. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was a randomized controlled trial comparing two opioids. Twelve studies investigated administration of opioids orally (n=3,040), 5 transdermally (n=1,628), and 10 intrathecally (n=231).

Within each modality, a portion of participants discontinued opioid therapy due to side effects (oral, 22.9%; transdermal, 12.1%; intrathecal, 8.9%). To a lesser extent, insufficient pain relief was a cause of discontinuation (oral, 10.3%; intrathecal, 7.6%; transdermal, 5.8%). Serious adverse events were rare and signs of opioid addiction were reported in only 0.27% of participants in the studies that reported that outcome. All 3 modes of administration were associated with clinically significant reductions in pain in the majority of patients, but the amount of pain relief varied across studies. Findings regarding quality of life and functional status were inconclusive due to an insufficient quantity of evidence for oral administration studies and inconclusive statistical findings for transdermal and intrathecal administration studies.

CLINICAL COMMENTARY: Cochrane reviews — following well-developed protocols for data search, extraction, analysis, and validation of findings — are perhaps the most rigorous and robust approaches for assessing current knowledge of particular therapies. In this analysis of studies evaluating long-term opioids for chronic noncancer pain, both the quantity and quality of evidence were disappointing; so, clearly, better and longer-term trials are needed to help identify patients who are most likely to benefit.

Most of the patients in the reviewed studies had chronic back pain following failed surgeries, severe osteoarthritis, or pain related to nerve damage, so the findings cannot be extended to other conditions such as headache, fibromyalgia, etc. Opioid analgesia was not ideal for all patients; some discontinued therapy (especially oral opioids) due to side effects or insufficient pain relief; however, it is unknown whether they transferred to alternate opioids or administration regimens with greater success after dropping out of the respective studies.

Among studies assessing opioid abuse or addiction, only 7 of 2,613 patients (0.27%) developed such opioid-use problems, and the researchers estimated that the rate would be merely 0.14% if no addictive behaviors occurred among studies that did not report addiction rates at all (which seems speculative). Our own review of studies reporting rates of opioid analgesic abuse/addiction in patients with pain found a range of 0.19% to 3.7% (see PDFs at [Leavitt 2007, p. 1] and [Leavitt 2008, p 6]). While there have been inconsistencies across studies in definitions of abuse and addiction, or in distinguishing between patients with/without prior substance-use problems, the rates, even at the higher end, suggest that prescription-opioid abuse/addiction in patients with pain is not anywhere as severe or widespread as some authors and agencies have depicted. On the other hand, there have been some disturbingly high rates of illicit or unauthorized substance use (particularly marijuana) alleged in certain patient populations, but Noble et al. did not examine this concern. These issues need further and unbiased examination; meanwhile, during everyday practice, iatrogenic (therapy induced) opioid abuse or addiction might be considered as merely a rather rare side effect in very select patients.

REFERENCE: Noble M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane Database of Systematic Reviews. 2010;1(#CD006605) [abstract/summary].