Efficacy and Safety of Methadone as a Second-Line Opioid for Cancer Pain in an Outpatient Clinic: A Prospective Open-Label Study

Abstract

Introduction. Most clinical reports on methadone rotation describe outcomes in hospitalized patients. The few studies that have included outpatients are retrospective. The aim of this study was to assess the efficacy and safety of methadone as a second‐line opioid in adult patients with advanced cancer after rotation in routine clinical practice at a palliative care outpatient clinic. Patients and Methods. This was a prospective, open‐label study of 145 patients whose treatment was rotated from other opioids to methadone. Informed consent was obtained in all cases. The main outcome measure was change in the variable “worst pain” at day 28. Pain and pain interference were assessed with the Brief Pain Inventory, with side effects evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Pain levels were evaluated at study entry and at days 3, 7, 9, 14, 21, and 28. Results. Rotation to methadone was performed for the following reasons: poor pain control (77.9%), opioid side effects (2.1%), or both (20%). The mean daily oral morphine equivalent dose before rotation was 193.7 mg. The median worst and average pain scores decreased significantly (p < .0001) from baseline to day 28: The median worst pain score decreased from 9 (interquartile range [IQR]: 8–10) to 6 (IQR: 3–8), and the median average pain score decreased from 6 (IQR: 5–7) to 4 (IQR: 2–5). The proportions of patients with moderate to severe worst and average pain decreased by 30.3% and 47.5%, respectively, by day 28. No increase in opioid toxicity was observed during the study. Conclusion. In outpatients with advanced cancer, rotation to methadone as a second‐line opioid was efficacious and safe when using a tiered scheme with close follow‐up by experienced health professionals. Implications for Practice: The results of this study, conducted prospectively under real clinical conditions, support the efficacy and safety of oral methadone as a second‐line opioid in ambulatory patients with cancer. Moreover, these findings corroborate previously reported outcomes in retrospective outpatient studies and prospective studies that evaluated inpatient populations. Although more research into methadone rotation strategies is still needed, this study describes a successful tiered scheme of oral methadone rotation that was proven safe and effective during follow‐up.

A single‐institution, randomized, pilot study evaluating the efficacy of gabapentin and methadone for patients undergoing chemoradiation for head and neck squamous cell cancer

“…32 Recently, a prospective study of 145 patients with advanced cancer who were treated in an outpatient palliative care clinic with rotation to methadone found a significant improvement in pain relief without an increase in opioid toxicity. 33 In 2013, a federally convened expert panel developed a consensus statement regarding methadone induction and stabilization. The comprehensive report offered specific recommendations for initiating methadone treatment and concluded that methadone can be safely prescribed provided the risks are recognized, there is adequate patient education, and there is a plan of intervention at signs of toxicity.…”

“…A prior retrospective analysis has shown that the outpatient administration of methadone in patients with cancer is considered safe and has a side effect profile similar to that of other opioids . Recently, a prospective study of 145 patients with advanced cancer who were treated in an outpatient palliative care clinic with rotation to methadone found a significant improvement in pain relief without an increase in opioid toxicity . In 2013, a federally convened expert panel developed a consensus statement regarding methadone induction and stabilization.…”

Malignant psoas syndrome associated with gynecological malignancy: Three case reports and a review of the literature

“…A simple analgesic agent is often ineffective, and multimodal pharmacotherapy, including opioids, non-opioid analgesics, and adjuvant drugs (antiepileptics, antidepressants, and muscle relaxants), is required, although its effectiveness has been shown to be limited (2,3). Recent studies have shown that rotation switching of opioids to methadone was effective for refractory neuropathic pain (6,20). Other studies reported the efficacy of intervention strategies, including epidural analgesia (9,19), injection from a psoas sheath catheter (21) or intrathecal catheter (19,22), and dorsal rhizotomy (23).…”

Best Practices in the Management of Nonmedical Opioid Use in Patients with Cancer-Related Pain

“…Because of incomplete cross‐tolerance between different types of opioids, rotation is effective in reducing MEDD while improving analgesia and maintaining tolerance to severe side effects such as respiratory depression. Rotation to a specific opioid also indicated for the pharmacological treatment of dependence (methadone or buprenorphine) may provide additional risk reduction. Opioid rotation is successful in about two thirds of patients with cancer, resulting in a decreased MEDD, accompanied by improved pain, depression, overall well‐being , and survival .…”