Case
“Ruth” is 79 and a retired music teacher. She had curative intent chemotherapy for lymphoma five years ago but was otherwise healthy all her life. She currently lives with her husband of 59 years, who has mild cognitive impairment. She has chemotherapy-induced peripheral neuropathy (CIPN) which has not improved further from the level it reached by about six months following completion of the cancer treatment. She has continuous painful tingling and burning sensations in her fingers and the soles of her feet that is made worse by pressure, for example getting out of bed in the morning, or pressing the foot pedals on her piano – her preferred musical instrument. She has had to stop playing multiple instruments because of pain in her fingers. She has also had difficulty with activities that require fine motor skills, including some cooking tasks.
For pharmacotherapy Ruth has tried gabapentin, which made her feel drowsy, nauseated and unsteady on her feet with minimal improvement in the pain, so she stopped taking it after a good trial of increasing doses. She is on 10 mg of nortriptyline at bedtime, which she says does help a little – approximately by 20%, but not sufficiently to allow her to play music again, her biggest source of joy. She has tried higher doses but says more does not give her better pain relief. She has also tried duloxetine but found it more sedating than nortriptyline and no more effective. Acetaminophen has no effect. Ruth rates her pain at 6-9/10 and is becoming concerned about her ability to care for her husband because of her pain and functional limitation. She does not want to take anything that might affect her cognition but does comment that when she was having treatment, she took some oxycodone which was quite helpful, but she stopped it after she had been discharged from her cancer centre. She was told that she shouldn’t be taking any opioid medication for non-cancer pain.
She is not diabetic, her B12 level is in the middle of the normal range and there are no other reasons for her to have peripheral neuropathy.
Issue
This story illustrates the dangers of creating a false dichotomy between “cancer pain” and “non-cancer pain”.
Background/Evidence
It is clear that many chronic pain syndromes that our patients must live with may not be very opioid-responsive, for example osteoarthritis, irritable bowel syndrome and most low-back pain. It is also clear that some people with cancer can live for a long time, either with “controlled” or very slow-growing cancer, or with the painful after-effects of successful cancer treatments. The boundary between what is and isn’t an appropriate situation to consider opioid therapy is blurred and with considerable overlap.
The most recent update of the Canadian Guideline for opioid therapy and chronic non-cancer pain was produced in 2017.1 The guideline’s second recommendation was “for patients with chronic non-cancer pain, without current or past substance use disorder and without other active psychiatric disorders, who have persistent problematic pain despite optimized non-opioid therapy, we suggest adding a trial of opioids rather than continued therapy without opioids (weak recommendation).” The guideline clearly stated that it did not apply to cancer pain or those approaching end of life. It also reminded readers that no guideline can account for the unique features of patients and their clinical circumstances, and that it was not meant to replace clinical judgment. Unfortunately, the guideline has been widely misapplied and patients have been denied appropriate care based on the over-simplification that opioid prescribing for non-cancer pain was always bad medical practice instead of just sometimes.2
The main opioid choices we have in Canada are:
- morphine
- hydromorphone
- oxycodone
- transdermal fentanyl
- methadone
- transdermal buprenorphine
Each opioid has its own advantages and disadvantages. There are also variabilities in individuals’ responses, either genetically predisposed to, or because of differing pain mechanisms in different conditions, and sometimes a switch from one opioid to another can provide better outcomes.
Morphine has a broad spectrum of opioid receptor effects and is available cheaply in multiple low-dose and sustained release formulations, but its metabolites are cleared renally and in the elderly there is a higher risk of renal impairment that makes it not the first choice that it would be in younger individuals.
Hydromorphone long acting’s lowest strength (3 mg) is approximately equivalent to 15mg morphine, so it is harder than morphine to titrate. It is also more expensive.
Oxycodone is similarly effective to morphine,3 and may be less sedating, but also has issues with long-acting coverage and minimum pill strengths.
Transdermal fentanyl is inappropriate for low-dose therapy or for opioid initiation due to the smallest patches still delivering a potentially large dose of the drug and unpredictability in absorption. Fentanyl can also be poorly effective in neuropathic pain.
Transdermal buprenorphine is a good choice for neuropathic pain and is available in low strength patches but is often unaffordable.
Methadone is an excellent choice for chronic and neuropathic pain. In addition to its broad spectrum of opioid receptor activity it has other effects, such as blocking the NMDA receptors involved in “Wind Up,” or secondary sensitization. It can be started in tiny doses and very finely, slowly adjusted according to effect. It can have drug interactions (the “grapefruit-list” drugs), but these are usually able to be avoided. It can also prolong the QT interval in high doses, but doses are almost always low when managing opioid-sensitive pain in the absence of a preceding opioid use disorder.
Case Outcome
Ruth was started on 0.5 mg methadone every eight hours, which provided very meaningful pain relief and allowed her to return to playing music. After two weeks she increased the morning dose to 1 mg but left the afternoon and evening doses at 0.5 mg. She took an occasional sennosides for mild constipation but otherwise tolerated methadone very well. On methadone she rated her pain between 0 and 2/10 with normal activities. She remained on it with good effect and no dose escalation until her death from a stroke seven years later.
References
- Busse JW, Craigie C, Juurlink DN, Buckley DN, Wang L, Couban RJ, Agoritsas T, Akl EA, Carrasco-Labra A, Cooper L, Cull C, da Costa B, Frank JW, Grant G, Iorio A, Persaud N, Stern S, Tugwell P, Vandvik PO and Guyatt GH. Guideline for opioid therapy and chronic noncancer pain. CMAJ May 08, 2017 189 (18) E659-E666; DOI: https://doi.org/10.1503/cmaj.170363
- Clarke H, Bao J, Weinrib A, Dubin RE, Kahan M. Canada's hidden opioid crisis: the health care system's inability to manage high-dose opioid patients: Fallout from the 2017 Canadian opioid guidelines. Can Fam Physician. Sep 2019;65(9):612-614. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741787/
- Guo, KK., Deng, CQ., Lu, GJ. et al. Comparison of analgesic effect of oxycodone and morphine on patients with moderate and advanced cancer pain: a meta-analysis. BMC Anesthesioly 18, 132 (2018). https://doi.org/10.1186/s12871-018-0583-8.
Additional Clinical Resources
Methadone4pain free fully CME-accredited online course, with certificate of completion after successfully completing a quiz. It takes about 1hour. Hosted at the Canadian Virtual Hospice’s Learning Hub. https://www.virtualhospice.ca/learninghub.
