The Use of Low-Dose Methadone as Add-On to Regular Opioid Therapy in Cancer-Related Pain at End of Life: A National Swedish Survey in Specialized Palliative Care

Abstract

Background: Low-dose methadone in addition to another ongoing opioid therapy is a promising approach for managing complex cancer-related pain and is, despite limited evidence, used in clinical practice. Objective: To investigate the use of low-dose methadone in specialized palliative care in Sweden. Design: Specialized palliative care services in Sweden answered a survey regarding methadone use in individual patients over 12 months. Setting/Subjects: The survey was an add-on to the Swedish Register of Palliative Care's (SRPC) mandatory end-of-life questionnaire (ELQ). Results: Sixty of 133 invited units (45%) participated in the study. A total of 4780 ELQs were registered. Four hundred ten of these patients received methadone (9%). In 96% of these patients, methadone was prescribed as an add-on to ongoing opioid therapy, mostly because of poor pain control due to mixed nociceptive and neuropathic pain (70%). Methadone was used for a median of 21 days, in 86% of cases until death. Mean daily methadone doses increased from 7 mg at start to 21 mg (p < 0.005) during the last 24 hours. Corresponding morphine equivalent daily doses of other opioids were 184 and 199 mg (p < 0.05), respectively. A pain-relieving effect was reported in 94% of the patients. Adverse effects were seen in 20% of the patients; none of these was severe. Conclusion: The addition of low-dose methadone to an ongoing opioid therapy in patients with complex cancerrelated pain is well established in Swedish specialized palliative care. It appears to have good pain-relieving effects and to be safe.

Methadone in Swedish specialized palliative care—Is it the magic bullet in complex cancer-related pain?

“…According to our informants, initiation of low-dose add-on methadone in a home care setting has become routine and provides a great advantage over having to admit the patient for rotation on a ward. This finding is in line with our previous reporting from 2020, where we described how a third of methadone initiations in specialized palliative care in Sweden were performed at home [18].…”

“…Methadone was highlighted as an important component of the palliative toolbox because it was easy to handle and had rapid onset, often within a few hours. The notion of methadone treatment being successful in 50-90% of selected patients is mainly in line with previous reports of the effects of low-dose methadone add-on therapy [15,18,35,36].…”

“…There is emerging evidence that low-dose methadone as an add-on twice daily to already existing high-dose opioid treatment increases the pain-relieving effect in complex pain [14][15][16][17][18]. This is also the general opinion in the current study.…”

“…In specialized palliative care in Sweden, 96% of patients using methadone receive it in the form of low-dose add-on, above all to take advantage of its presumed NMDA-receptor inhibitory effect [18]. Low-dose add-on was, by our informants, considered a simple and manageable way of obtaining the desired effects.…”

“…This is of particular interest in complex pain syndromes. In such cases, combining an ongoing high-dose opioid treatment with a low fixed dose of methadone has become increasingly popular in specialized palliative care, not least in Sweden [14][15][16][17][18]. Still, the appropriate indications for, as well as practical uses of, low-dose methadone have been insufficiently defined.…”