Efficacy and safety of adjunct methadone with opioid therapy for cancer pain: a systematic review.

Authors

Philip Austin, Marco Lamonaca, Kenny Kwon Ho Lee, Jessica Lee, Aaron Wong, Hiromichi Matsuoka, Jisu Kim, Malama Tafuna'i, Tim Luckett, Wei Lee

Published in

Journal of pain and symptom management. Oct 07, 2026. Epub Oct 07, 2026.

Abstract

The use of opioid analgesia for cancer-related pain is challenging. Adequate pain relief is not always achieved where prolonged prescription of opioids carry risks including adverse effects, tolerance and hyperalgesia. Recent studies suggest that methadone as an adjunct to ongoing opioid therapy is effective in reducing pain severity without increases in adverse effects.
To systematically evaluate current evidence of the efficacy, safety and tolerability of adjunct methadone in combination with ongoing opioid regimens for cancer-related pain.
A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify studies that evaluated the efficacy, safety and tolerability of adjunct methadone with ongoing opioid regimens for cancer-related pain.
Of 4680 articles located, 13 studies including 641 participants (mean age 62.8 years, 53% male) were accepted for review. Included studies comprised of one RCT, three prospective open-label studies, five retrospective observational studies and four case reports. Despite low-quality evidence, findings from all studies report that adjunct methadone offers meaningful analgesic benefit. Ten studies also report adverse effects, however, only a few cases were noted as severe.
This is the first systematic review to synthesise evidence from current literature on the efficacy of adjunct methadone with ongoing opioid regimens for cancer-related pain. Although findings across all studies suggest analgesic benefit for cancer-related pain, high-quality, larger-scale RCTs are required to better inform clinical recommendations.

PMID:
42843430
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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