Meredith Noble

Long-Term Opioid Therapy for Chronic Noncancer Pain: A Systematic Review and Meta-Analysis of Efficacy and Safety

Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term efficacy and adverse events (including addiction). We systematically reviewed the clinical evidence on patients treated with opioids for CNCP for at least six months. Of 115 studies identified by our search of eleven databases (through April 7, 2007), 17 studies (patients [n]=3,079) met inclusion criteria. Studies evaluated oral (studies [k]=7; n=1,504), transdermal (k=3; n=1, 993), and/or intrathecal (k=8; n=177) opioids. Many patients withdrew from the clinical trials due to adverse effects (oral: 32.5% [95% confidence interval (CI), 26.1%-39.6%]; intrathecal: 6.3% [95% CI, 2.9%-13.1%]; transdermal: 17.5% [95% CI, 6.5%-39.0%]), or due to insufficient pain relief (oral: 11.9% [95% CI, 7.8%-17.7%]; intrathecal: 10.5% [95% CI, 3.5%-27.4%]; transdermal: 5.8% [95% CI, 4.2%-7.3%]). Signs of opioid addiction were reported in only 0.05% (1/2,042) of patients and abuse in only 0.43% (3/685). There was an insufficient amount of data on transdermal opioids to quantify pain relief. For patients able to remain on oral or intrathecal opioids for at least six months, pain scores were reduced long-term (oral: standardized mean difference [SMD] 1.99, 95% CI, 1.17-2.80; intrathecal: SMD 1.33, 95% CI, 0.97-1.69). We conclude that many patients discontinue long-term opioid therapy due to adverse events or insufficient pain relief; however, weak evidence suggests that oral and intrathecal opioids reduce pain long-term in the relatively small proportion of individuals with CNCP who continue treatment.

Opioid Pharmacotherapy for Chronic Non-Cancer Pain in the United States: A Research Guideline for Developing an Evidence-Base

UNLABELLED This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence. PERSPECTIVE Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP.