End-of-dose pain in chronic pain: does it vary with the use of different long-acting opioids?

A large percentage of patients with chronic pain on around-the-clock (ATC) opioids may experience increased pain occurring at the end of a scheduled dose, also known as end-of-dose pain. Despite the significant prevalence and impact of end-of-dose pain in patients using extended-release (ER) opioids, there are no detailed analyses examining how the frequency of end-of-dose pain is linked to the formulations of long-acting opioids. Consequently, we performed a systematic review to evaluate how many published studies on patients with chronic cancer or noncancer pain identified end-of-dose pain. As only a few studies mentioned end-of-dose pain explicitly, we used breakthrough pain (BTP) as a surrogate parameter. We determined if any opioid formulation had a greater association with the frequency of BTP, the use of rescue medication for BTP, and the frequency of end-of-dose pain. Of the 39 studies entered in the final analysis, 14 studies across different formulations showed that ER opioids were effective in the prevention of BTP. The opioids most frequently studied were hydromorphone (26%), followed by morphine (23%), and transdermal buprenorphine (23%). Only 5% of the studies used immediate-release preparations. Overall, most studies showed that patients using ER preparations experienced fewer episodes of BTP compared with patients on placebo or an active comparator. This could reflect the favorable duration of action of these opioids compared with short-acting formulations. Future studies should examine the incidence of end-of-dose pain and use of rescue medicine in a longitudinal manner in patients with chronic pain taking short- vs. long-acting ATC opioids.