We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was an RCT comparing two opioids. Opioids were administered orally (number of study treatments groups [abbreviated as "k"] = 12, n = 3040), transdermally (k = 5, n = 1628), or intrathecally (k = 10, n = 231). Many participants discontinued due to adverse effects ( oral : 22.9% [95% confidence interval ( CI ): 15.3% to 32.8%]; transdermal: 12.1% [95% CI : 4.9% to 27.0%]; intrathecal: 8.9% [95% CI : 4.0% to 26.1%]); or insufficient pain relief ( oral : 10.3% [95% CI : 7.6% to 13.9%]; intrathecal: 7.6% [95% CI : 3.7% to 14.8%]; transdermal: 5.8% [95% CI : 4.2% to 7.9%]). Signs of opioid addiction were reported in 0.27% of participants in the studies that reported that outcome . All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among 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.

