neurology recs: chronic noncancer pain management

the American Academy of Neurology just published a position paper on the use of opioids for chronic noncancer pain, or CNCP, lasting more than 3 months (see opioid guidelines neurology 2014 in dropbox, or doi: 10.1212/WNL.0000000000000839). their basic argument is that there are no data showing that longer term opioids are effective (though they do acknowledge that none of the randomized controlled trials lasted more than a few months). a cross-sectional Danish study found that those with chronic pain on opioids reported that over time they had decreased pain relief, functional capacity and quality of life vs those not on opioids, "adjusting for severity" (i'm not sure what that means. a little hard to imagine that they can really adjust for severity accurately in an observational study with the subjective endpoint of pain. and i would imagine a huge selection disadvantage if you look at those patients who had been put on opioids). the best intervention study i have found is a VA study looking at stable vs escalating doses of opioids for CNCP (see chronic pain stable vs escalating dose jpain 2011​ in dropbox file on "chronic pain", or doi:10.1016/j.jpain.2010.09.003), which found that 135 patients already on opioids for pain relief and referred to a pain clinic (94% male, 74% with musculoskeletal pain) were randomized to Stable dose vs Escalating dose of opioids, with escalation only if pain not adequately treated, at the discretion of the prescribing MD, and with no change in pill appearance. they found that those in the Escalating dose group had no change in pain or functional disability, but did have a improvement in usual pain (nonsignificant) and amount of relief (small but significantly decreased self-reported pain score with dose escalation) but not with the Oswestry disability index. and 27% were discharged from the study for opioid misuse (no diff between the groups). BUT the Stable group went from 32 morphine-equivalent doses in the beginning of the study to 40 (not sure why??), whereas the Escalating dose group went from 32 morphine-equivalents in the beginning of the study to only  50 at the end (ie, not much of an escalation...).

the neurol academy does recommend the routine stuff: opioid treatment agreement, screen for prior/current substance misuse, screen for depression/anxiety/PTSD, random urine toxicology screens, not use concomitant benzos, track pain and function (best with validated instrument), track morphine equivalent doses (MEDs), use state prescription drug monitoring program.

but, in addition they recommend "avoid escalating doses above 80-120 mg/d MEDs unless sustained meaningful improvement in pain and function is attained, and not without consultation with a pain management specialist".

there are a few very important unresolved and very confusing issues for us chronic pain prescribers.
    ​--we all (i suspect) have patients with noncancer chronic pain who have clinically clearly responded to higher doses of opiates and not to lower doses. and there are NO studies in the literature (that i know of) which have addressed this issue in an objective manner (ie RCT where patients have received significantly increasing doses of opiates vs either placebo or stable low-dose opiates and assessing pain/disability outcomes).
    --neurophysiologically (i believe) there is no difference between cancer and noncancer chronic pain.  they both trigger pain the same receptors. And it seems we need to treat pain in either case.
    --we do know reasonably well that increasing opiate dosages are associated with increasing substance use disorders and aberrant medication-taking behaviors (though, of note, in the VA study cited above, the opioid misuse was no different in those on escalating vs stable opioids). of major concern is mortality associated with higher doses of opiates (again, no RCT i am aware of, just the association, raising the issue that those patients requiring really high doses may have other reasons for increased mortality than the opiates). and there are other well-known adverse effects of opiates including hypogonadism/infertility, falls/fractures in elderly, neonatal abstinence syndrome, prolonged QTc with methadone, opioid-induced hyperalgesia, etc). in terms of mortality (but remember this is only observational data): one study found a 9-fold increase in overdoses in those on >100 morphine-equivalents vs those <20 and other studies have confirmed increased risk if above 80-120 MEDs.
    --we do know with certainty that prescribing opiates does have the unfortunate unintended consequence of being associated with diversion, with the (also well-documented) dramatic increase in prescription opiate addiction/deaths in the community. the paper states that "over 100,000 people have died, directly or indirectly, from prescribed opioids in the US since the late 1990s"
    ​--that all being said, i have had some, though limited success (based on the likely increased mortality with increasing opioid dosages) in dramatically reducing the amount of morphine-equivalents in several patients, without significantly exacerbating the chronic pain

so, what is one to do with the patient in front of you with disabling chronic pain refractory to other meds/therapeutic modalities??  the short answer is probably: treat the patient with opioids, trying to keep the dosages as low as possible, periodically trying to lower the dosages in those patients on high doses, consider the advantages of other adjuvant therapies to keep the dose as low as possible (physical therapy, tricyclic antidepressants, other meds...), doing the appropriate screenings (urine tox screens, EKGs esp for those on methadone, and others as recommended above) and referring to pain clinics for their input on management of difficult, inadequately-responding cases. as a primary care physician seeing many patients with chronic pain, i do not think there is an arbitrary cutoff of 80-120 morphine-equivalents as the neurology society recommends (seems a bit self-serving  to recommend referrals to themselves as a requirement...). though in many difficult cases a pain clinic referral can be helpful.