Opioid-induced neurotoxicity after opioid conversion to methadone in patients with cancer pain using the stop-and-go...

To describe the frequency of opioid-induced neurotoxicity (OINT) after opioid conversion (OC) to methadone using the Stop-and-Go (SAG) method in cancer patients with inadequate pain control, and to identify factors associated with OINT.

This multicenter retrospective cohort study included adult hospitalized cancer patients who underwent OC to methadone using the SAG method for poor pain control at two comprehensive cancer centers between January 2018 and October 2022. Patients were monitored 14 days after OC, and variables related to OINT were analyzed. Ethical approval was obtained.

A total of 372 patients underwent OC using the SAG method. The mean morphine-equivalent daily dose (MEDD) before OC was 212.2 mg (SD 128). OINT occurred in 70 patients (18.8%). Methadone was permanently discontinued in 2 patients (2.8%) and temporarily withheld in 7, while 61 were managed with hydration and a 15-20% methadone dose reduction. No patient required naloxone. OINT was less frequent in younger patients (mean age 59.4 vs. 63 years; p = 0.032) and showed a trend toward lower incidence in women (13% vs.22%; p = 0.065). Preexisting cognitive impairment or delirium was associated with OINT (52.4% vs.16.8%; p < 0.001). The mean time from OC to death was shorter among patients with OINT (2.1 months; SD 3.9) compared with those without OINT (3.6 months; SD 6.4; p = 0.012).

OC to methadone using the SAG method in patients with low-to-moderate MEDD was associated with a relatively low OINT frequency (18.8%). These findings suggest that SAG method in patients with low-to-moderate MEDD before OC may be safe, particularly for younger patients and those without cognitive impairment.