A Review of the Use of Methadone for the Treatment of Chronic Noncancer Pain

Abstract

Methadone, although having been available for approximately half a century, is now receiving increasing attention in the management of chronic pain. This is due to recent research showing that methadone exhibits at least three different mechanisms of action including potent opioid agonism, N-methyl-D-aspartate antagonism and monoaminergic effects. This, along with methadone's excellent oral and rectal absorption, high bioavailability, long duration of action and low cost, make it a very attractive option for the treatment of chronic pain. The disadvantages of significant interindividual variation in pharmacokinetics, graduated dose equivalency ratios based on prerotation opioid dose when switching from another opioid, and the requirement for special exemption for prescribing methadone make it more complicated to use. The present review is intended to educate physicians interested in adding methadone to their armamentarium for assisting patients with moderate to severe pain.Key Words: Chronic pain; Methadone; Pharmacotherapy Une analyse de l'utilisation de la méthadone dans le traitement des douleurs non cancéreuses chroniques La méthadone, bien qu'elle soit disponible depuis environ un demi-siècle, attire plus d'attention dans la prise en charge des douleurs chroniques. Cet intérêt découle de recherches récentes selon lesquelles la méthadone comporte au moins trois mécanismes d'action différents, y compris un puissant agonisme des opiacés, un antagonisme N-méthyl-D-aspartate et des effets monoaminergiques. Ce phénomène, allié à l'excellente absorption orale et rectale de la méthadone, à sa biodisponibilité élevée, à sa longue durée d'action et à son faible coût, le rend très attrayant dans le traitement des douleurs chroniques. Les inconvénients d'une variation pharmacocinétique interindividuelle marquée, des ratios d'équivalence de doses graduées fondés sur la dose d'opiacés de prérotation au moment de changer d'opiacé et le besoin d'une exemption spéciale pour prescrire de la méthadone en compliquent l'utilisation. La présente étude vise à informer les médecins intéressés à ajouter la méthadone à leur panoplie pour aider les patients ayant des douleurs modérées à graves.

The Pharmacotherapy of Chronic Pain: A Review

“…Methadone exhibits significant inter-individual variation in pharmacokinetics as well as incomplete cross-tolerance with conventional opioids, and it is important for clinicians to be aware of this in some detail so that patients are not exposed to unnecessary risk when switching from conventional opioids to methadone. A review of the use of methadone in chronic noncancer pain containing details has recently been published in Pain Research & Management (178). Of note, methadone powder is used to prepare a liquid methadone in a concentration requested by the physician.…”

“…Methadone ranges from four to 12 or more times the potency of morphine, the relative potency of methadone is higher with higher doses of the previous conventional opioid. Care should be taken in opioid rotation especially if the patient is on high doses of a conventional opioid, lower relative doses of methadone will be required, for detailed conversion ratios see [178]; **Difficult to define equipotent dose because tramadol is only available in Canada in combination with acetaminophen. Tramadol has weak opioid agonist effects in a range similar to codeine, Tramacet tablets contain 37.5 mg of tramadol and 325 mg of acetaminophen, tramadol also exhibits monoaminergic effects, it is important to be aware of this in patients using antidepressants or other agents with monoaminergic action; † † Meperidine and pentazocine are not appropriate for chronic use.…”

Neuropathic pain: a practical guide for the clinician

“…93 However, its long half-life (24-36 hours) necessitates extremely careful dose titration. 94 Two small RCTs of methadone demonstrated benefit in managing neuropathic pain, 95,96 and open-label experience suggests promise in a wide variety of neuropathic pain conditions. 97 …”

A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone

“…5 Several case reports, as well as series of cases, have described the occurrence of a potentially fatal arrhythmia, torsade de pointes, with the use of methadone. This phenomenon has been attributed to cardiac potassium ion channel blockade by the drug, resulting in prolongation of cardiac repolarization and a prolonged QT-interval on the electrocardiogram.…”