Is levorphanol a better option than methadone?

Background Methadone has been a stalwart pharmacologic option for the management of opioid drug dependence for many years. It substitutes for opioid agonists and possesses certain pharmacokinetic properties that confer characteristics preferable to those of other opioids for this application. Methadone is likewise used as an option for the treatment of pain, particularly chronic pain. It has a spectrum of pharmacodynamic activity, including contributions from non‐opioid components, that translates to its specific clinical attributes as an analgesic. Unfortunately, basic science studies and accumulated clinical experience with methadone have revealed some undesirable, and even worrisome, features, including issues of safety. The benefit/risk ratio of methadone might be acceptable if there was no better alternative, but neither its pharmacokinetic nor pharmacodynamic properties are unique to methadone. Objective We review the basic and clinical pharmacology of methadone and suggest that levorphanol should receive attention as a possible alternative. Conclusion Unlike methadone, levorphanol is a more potent NMDA antagonist, possesses a higher affinity for DOR and KOR, has a shorter plasma half‐life yet longer duration of action, has no CYP450 interactions or QTc prolongation risk, can be a viable option in the elderly, palliative care, and SCI patients, requires little to no need for co‐administration of adjuvant analgesics, and has potentially a lower risk of drug‐related Emergency Department visits compared to other opioids.