Is there evidence to support the efficacy of long-term opioids for chronic pain?
Evidence to support the efficacy of long-term opioids for chronic pain is extremely limited.
No randomized trial of opioids vs placebo has treated patients for more than six months, and most treated patients for fewer than six weeks.
In a Cochrane review, there were very limited data from uncontrolled studies (eg, studies of patients originally randomly assigned to receive opioids in a clinical trial and then followed after the trial ended) that some proportion of patients do continue opioids long-term and report continued pain relief, although significant proportions also discontinued owing to adverse effects or lack of efficacy.
Clearly, more long-term controlled studies are needed to understand efficacy of long-term opioids vs alternative therapies (placebo, no opioid, and nonopioid alternatives).
How does one avoid opioid-induced hyperalgesia increased sensitivity to pain?
Data estimate the prevalence and clinical impact of hyperalgesia in humans, or how to avoid it, are quite limited. In clinical practice, it can be very difficult to distinguish hyperalgesia from tolerance. Some evidence suggests that hyperalgesia occurs at relatively high doses of opioids, and should be relatively uncommon at doses below 120 mg morphine equivalents per day. Some research suggests that blocking NMDA receptors (with such agents as dextromethorphan, ketamine, or methadone) may help prevent hyperalgesia, but a lot more research would be needed before using such drugs for these purposes could be recommended, because these come with their own potential harms
By the way for an other hand controlled studies, by their design, ignore an individual’s response. This is an important omission if we want to know how often an individual does well on opioid therapy for one, two, or more years and how often an individual does not. We need to design a more clinically relevant approach to studying this important matter.