UC Irvine

PurposeTo compare the effectiveness and side effects of methadone and other opioids when given as a breakthrough pain medication.

Patients and MethodsRetrospective chart analysis of hospitalized patients with severe pain requiring scheduled methadone for their constant pain, and either received methadone or “other opioid” (such as morphine, hydrocodone, oxycodone, hydromorphone, or fentanyl) as their breakthrough “as-needed” (PRN) pain medication from November 2017 to January 2022. The methadone PRN pain medication group was compared to a similar group of randomized patients requiring “other opioid” PRN group over the same time period.

ResultsA total of 207 inpatients who required scheduled methadone was compared in two cohorts, either prescribed methadone PRN for breakthrough pain (n = 101) or “other opioid” PRN for breakthrough pain (n = 106) for 1,712 total PRN administrations (n = 484 and 1,228, respectively). The groups were well matched, but more prevalent in those with renal disease; and statistically significant more younger patients and those with polysubstance use disorder received methadone PRN. Both methadone and “other opioid” PRN pain cohorts had similar PRN opioid milligram (mg) equivalents (OME) (mean 35.68, SD 30.25 and mean 38.54, SD 30.86, respectively) per day, additional adjuvant pain medications (2.4 and 2.8, respectively) and had similar pain score reduction effectiveness [mean pain difference -2.34 (SD 2.09) and -2.27 (SD 2.03, respectively]. Neither PRN medication group exhibited a statistically significant difference in typical side effects, such as nausea, pruritus, respiratory depression, altered mental status, or the more serious Rapid Response Team (RRT) assessments or naloxone administrations for opioid toxicity.

ConclusionMethadone PRN was as an effective analgesic compared to “other opioids” PRN when used as a breakthrough pain medication. It did not have more side effects or serious life-threatening events. Treating severe pain with methadone PRN may be advantageous when treating seriously ill patients and specific comorbidities. These comorbidities include the presence of polysubstance use disorder, especially heroin or opioid use disorder; and those with poor or worsening renal function. It also has unique pharmacological properties over other opioids because methadone does not require renal excretion, has few active metabolites, and is minimally removed by dialysis. Additionally, its liquid formulation allows for precise titration, and feeding tube access, and a sublingual route when there is loss of IV access or oral route.