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.