The Use of Low-Dose Methadone as Add-On to Ongoing Opioid Treatment in Palliative Cancer Care—An Underrated Treatment?

Abstract

The aim of this review is to summarize the current knowledge of low-dose methadone treatment in palliative cancer care. In Sweden, methadone is quite common in specialized palliative care, where almost a tenth of patients are prescribed this drug. Negative attitudes towards methadone do not seem to prevent it from being used for pain management, and by starting with low doses and then increasing slowly and gradually, methadone can apparently be introduced safely. It is still uncertain whether methadone has a better analgesic effect than other opioids. However, for pain relief in cancer patients with severe and complex cancer-related pain, NMDA receptor inhibition with methadone may, in selected cases, be an attractive alternative, especially in the form of low-dose supplements to other ongoing opioids. Due to long half-life and complex metabolism, the use of methadone requires an experienced physician and solid follow-up. Continuous administration of opioids, including low-dose methadone, has been proven effective and safe in reducing pain in dying patients without increasing the risk of confusion, regardless of age.

Methadone dose escalation in patients with opioid use disorder and cancer as a strategy for controlling cancer-related pain: A case series

“…Healthcare professionals facing a patient with OUD and cancer should obtain a series of information such as the history, the frequency, and the methods of drug use (McNally and Sica 2021). In fact, the control of OUD symptomatology is crucial for compliance and adherence to cancer treatments and to decrease the risk of serious complications (McNally et al 2019;2022;McNally and Sica 2021).…”

“…Methadone is an opioid drug with high affinity for 𝜇 and 𝛿 opioid receptors and acts as an NMDA receptor antagonist. NMDA receptors are involved in allodynia, hyperalgesia, opioid tolerance, and neuropathic pain, and methadone could exert some adjunctive extra-opioid analgesic action blocking NMDA receptors (Fürst 2022). Moreover, methadone induces a long-lasting analgesia, has high potency, has high oral bioavailability, and is relatively safe in patients with renal impairment (Ding et al 2022;Paice et al 2023).…”

“…The 2 months dose increase in the 2 groups was limited (35% and 15%, respectively) (Mercadante et al 2022). Moreover, low dose methadone was proposed as an add-on therapy in patients already taking an opioid (other than methadone) but with insufficient pain control (Fürst 2022). In fact, the adjunct of methadone with another drug may enhance analgesia and limit ADRs (Hanna and Senderovich 2021).…”

“…In fact, the adjunct of methadone with another drug may enhance analgesia and limit ADRs (Hanna and Senderovich 2021). In these cases, the dose of methadone is usually very low at the beginning (1-5 mg/day) and after titration not higher than 20 mg/day (Fürst 2022).…”