Background and Aims Adequate analgesia can be challenging, as pharmacological options are not necessarily effective for all types of pain and have various side effects. Methadone is increasingly being considered in the management of both cancer- and non-cancer-related pain.

Objective: To summarize the evidence on the effectiveness of methadone and review the side effects and cost of this drug.

Methods PubMed, Medline, Embase, and Google Scholar databases were searched to identify Randomized Controlled Trials (RCTs) assessing methadone and a comparison drug.

Results A total of 40 RCTs were included. The majority compared methadone to morphine or fentanyl. Methadone was effective in certain orthopedic, spinal, and cardiac surgeries. It was superior to fentanyl in the management of head-and-neck cancer pain. There was variability in the limited data on the management of neuropathic pain. Side effects experienced with methadone use were similar to a comparison drug.

The effectiveness of methadone in the management of post-surgical and cancer pain was dependent on the procedure and cancer type, respectively. Methadone may be useful as an adjunctive analgesic, to lower the dose of another drug

Conclusions Methadone may be a valuable in the management of post-surgical, cancer, or nociceptive pain, and in patients with renal impairment. Prescribers should consult a specialist prior to starting or discontinuing methadone.

Future Research: Reported outcomes for measuring analgesia must be standardized. Patients should be stratified by procedure and cancer type in future RCTs.