Early Use of Methadone for Cancer Pain

Abstract

Methadone has been known since the beginning of the 20th century. Its use for cancer pain is still controverted.Several articles clearly show the benefit of methadone for cancer pain. We attempted to identify the advantages of use of methadone early on in the course of cancer. Methadone is a very interesting molecule for cancer pain treatment because of anti NMDA, SSRI and opioid actions, lack of active metabolite, and cost. Its benefits must be balanced against the potential drug to drug interactions during treatment initiation and interactions with other drugs when methadone doses are stable. As for all opioids, side effects can appear. Ten studies including 706 patients support the use of methadone as first line opioid treatment: 7 are prospective studies (one double-blind randomized with morphine, 4 randomized controlled with morphine or transdermal fentanyl, two open studies) and 3 are retrospective studies. Seven studies support its ambulatory initiation (3 prospective including 2 controlled studies, and 4 retrospective studies) with a total of 845 patients. Methadone could be used with caution early on in cancer pain management.

Methadone in Cancer Pain

“…[ 1 ] Although studies have established safety as well as non-inferiority of methadone compared with its opioid counterparts when used as first line opioid in cancer pain, evidence is not yet robust to recommend it. [ 1 37 ] The challenge is in accepting methadone as a main stream first line opioid, from being considered as a second line replacement/substitution drug all these years. [ 7 26 ] This can become practical by identifying methadone by its unique pharmacology, carefully done low dose initiation and gradual dose titration by an experienced palliative care clinician, vigilant monitoring for QTc prolongation and respiratory depression, proper patient selection, minimizing drug interactions, advocating a safety checklist and formulating opioid rotation protocols could go a long way in establishing safety of methadone as a first line opioid in cancer pain management.…”

“…[ 1 ] Methadone needs to be considered early in cancer pain management rather than to reserve it for later stages when opioid tolerance has already set in, needing consideration for undertaking an opioid rotation. [ 37 ] It has been reported that 50-80% patients with cancer pain demonstrated improved pain control after addition of methadone. [ 38 39 40 ] Methadone has been a revelation in the management of complex pain, which usually is a combination of nociceptive and neuropathic components occurring towards end of life care, where poor pain control is often associated.…”