Low-dose add-on methadone for cancer pain management: a retrospective analysis of 102 Japanese patients

Methadone was introduced in 2013 for the treatment of intractable cancer pain in Japan and is indicated for patients receiving opioid doses ≧60 mg/day as an oral morphine equivalent. Low-dose (≦10 mg/day) add-on methadone to prior opioids has been reported from European countries to successfully relieve various types of intractable cancer pain; however, there are few reports of such use in Japan. The aim of this study was to analyze more than a hundred cases with low-dose add-on methadone to treat intractable pain in Japanese cancer patients.

All cases in which 5 or 10 mg/day of methadone was added to prior opioids by the Palliative Care Team or Division of Palliative Medicine in our hospital during the period between April 2016 and September 2023 were extracted and analyzed retrospectively on electrical medical charts.

A total of 102 cases were extracted with a male-to-female ratio of 60:42, and the age (mean ± SD) was 62.8 ± 14.7 years old. Methadone was introduced in an inpatient setting to 86 patients. The major pathologies that caused intractable pain were spinal metastases in 48, pelvis or pelvic floor lesions in 29 and pleural and/or chest wall lesions in 16. The most common mechanism of pain was the mixture of somatic and neuropathic components. The major opioids administered prior to methadone included tapentadol in 46 patients, hydromorphone in 36 and oxycodone in 19. The dose of the prior opioids [median, (interquartile range: IQR)] was 97, (62.8-167.3) (range: 15-1313) mg/day of oral morphine equivalent. Radiotherapy, chemotherapy and nerve blocks were performed as concomitant therapies in 48, 22 and 11 patients, respectively (with some overlap). The number of rescue doses [median (IQR)] was significantly decreased from three (two to five) on the day before methadone to one (zero to four) after seven days from methadone initiation. The side effects leading to discontinuation of methadone were drowsiness in three cases, nausea in three cases and dizziness in one case (with some overlap). Compared with complete switching from other opioids, low-dose add-on methadone can reduce the possibility of major dose discrepancies and can be quickly adjusted by combined opioid reduction/increase. Low-dose add-on methadone can be an effective and safe method for intractable cancer pain.