Major Finding: When opioids were used long-term for noncancer pain, 6%-23% of patients stopped taking them due to inefficacy or side effects and 0.3% developed signs of addiction.
Data Source: Cochrane Collaboration review of 26 clinical studies with 4,893 participants.
Disclosures: None.
One of the first systematic reviews of data on long-term use of opioids found weak evidence to support the idea that adults who can take chronic opioids get chronic pain relief, though effects on function or quality of life are unclear.
In a Cochrane Collaboration review of 26 prospective studies with 4,893 participants, 6%-23% of patients dropped out of the clinical trials (depending on the route of drug administration) due to inefficacy or side effects, but those who finished the studies maintained clinically significant reductions in pain during up to 48 months of opioid use, Meredith Noble and her associates reported.
The review also suggested that opioid abuse or addiction were rare, but acknowledged that the findings are compromised by the limited quantity and poor quality of the studies. Only 7 (0.3%) of 2,613 patients developed signs of addiction or took their medicine inappropriately in the studies that reported those outcomes (Cochrane Database Syst. Rev. 2010 [doi: 10.1002/ 14651858.CD006605]).
Most of the studies excluded patients with risk factors for abuse. The low rate of addiction may be generalizable only to patients with no history of abuse or addiction, wrote Ms. Noble, a senior research analyst at the Economic Cycle Research Institute, one of 14 evidence-based practice centers under the U.S. Agency for Healthcare Research and Quality. A previous study suggested that addiction or abuse may develop in 3% of patients in all studies of opioid use for chronic pain and in 0.2% of patients in studies that screened out participants with a history of abuse or addiction (Pain Med. 2008;9:444–59).
The evidence of long-term relief of noncancer pain with chronic opioid use was too sparse in the current review to draw firm conclusions about the treatment's effectiveness, including any quantification of mean level of relief from noncancer pain, the investigators concluded. All of the studies had low internal validity, making it highly likely that future studies could overturn their findings.
Among 3,040 patients treated with oral opioids, 23% discontinued treatment due to adverse effects and 10% dropped out of the trials because of insufficient pain relief. Among 1,628 on transdermal opioids, 12% stopped due to adverse effects and 6% stopped due to insufficient pain relief. Intrathecal pumps delivered opioids in 231 patients who could not find pain relief any other way; of these, 9% stopped due to adverse effects and 8% dropped out due to insufficient pain relief.
One of the studies in the review was a randomized trial comparing two opioids; the other 25 studies were case series or uncontrolled continuations of short-term trials of opioids for noncancer pain. None of the studies included comparisons with placebo or nonopioid therapies.
The only other systematic review of long-term opioid use for chronic noncancer pain was a 2008 study by the same investigators that used somewhat different methodology.
All of the patients had been taking opioids for at least 6 months after failing previous nonopioid therapy for noncancer pain of at least 3 months duration, mainly chronic back pain, severe osteoarthritis, or pain related to nerve damage.
Solid estimates are lacking for the number of people with chronic noncancer pain who are taking opioids long-term and what they are taking. Two U.S. studies suggest that 0.65% of people with medical insurance use opioids chronically and that 10% of people who claimed insurance coverage for opioids had at least a 3-month supply.
The Cochrane Collaboration is an international nonprofit, independent organization focused on systematic reviews of health care interventions.
However, three pain experts said in interviews that they fear clinicians might read too much into the review's limited findings.
The report is “very encouraging, but it's far from the whole story,” said Dr. Perry Fine said. A literature review doesn't necessarily reflect concerns in real-life practices. Because there are no good substitutes for opioids on the horizon, physicians need to find ways to make long-term opioid use more effective and safe, he said.
Dr. Fine, president of the American Academy of Pain Medicine (AAPM) and professor of anesthesiology at the University of Utah, Salt Lake City, compared current use of long-term opioids for noncancer pain with the use of surgical anesthesia 20–30 years ago when it was associated with significant morbidity and mortality.
“That didn't stop us from doing surgical procedures when necessary,” but it did motivate research and improvements in patient selection, monitoring, and dosing that led to the very low rates of morbidity and mortality with anesthesia today.