Low-dose methadone as add-on to ongoing opioid treatment in cancer-related pain

Abstract: Background: In complex cancer-related pain in imminently dying patients, even high doses of ordinary opioids may have an insufficient effect. The addition of low-dose methadone to another ongoing opioid has been proposed as a treatment option. The aims of this thesis were to study different aspects of low-dose add-on methadone to another ongoing opioid in specialized palliative care in Sweden. Patients, methods and results: In Study I, the medical records of 80 patients prescribed low-dose add-on peroral methadone to an ongoing opioid were assessed retrospectively. Eighty percent reached better pain control. Delirium and sedation increased near the end of life, but no serious adverse events were registered. In Study II, data on 4780 patients from 60 specialized palliative care units were analyzed. Methadone was safely prescribed, even in home care, to 8.6% of the patients (n=410), 96% of whom received it as a low-dose add-on for complex pain. In total, 94% were reported to benefit. Study III was a qualitative study to explore different aspects of methadone use. Semi-structured interviews were conducted with 30 physicians in specialized palliative care and pain medicine. Attitudes to methadone were reported not to affect its use as an analgesic and methadone was reported to achieve a best effect in situations of long-term opioid use with insufficient pain improvement and cases with central sensitization. Pain from skeletal metastases in the spine or pelvis were described to benefit particularly well. Cancer of the prostate, breast, kidney, pancreas, and sarcoma were reported as typical benefitting diagnoses. In Study IV, the daily symptoms of 93 imminently dying patients prescribed pain management via continuous subcutaneous infusion were followed. Improvement of pain, but unchanged prevalence of delirium, regardless of age, was seen in all patients. Low-dose add-on methadone was safely used in the patients with the highest initial pain. The daily median start dose of methadone in all studies was reported as 5 mg, increasing to a maximum of 20 mg. Discussion: Studies I-IV report that dying patients with complex cancer-related pain may obtain improved pain control from low-dose add-on methadone to another ongoing opioid, with limited side-effects. Attitudes to methadone seem not to be an obstacle to its use. Continuous subcutaneous infusion of opioids, including low-dose methadone, can effectively and safely reduce pain in the imminently dying patient without an increase of delirium, regardless of age. Overall, low-dose add-on methadone may be considered a valuable tool for pain management in selected patients with cancer-related complex pain in specialized palliative care.