Methods of Rotation From Another Strong Opioid to Methadone for the Management of Cancer Pain: A Systematic Review of the Available Evidence

Abstract

Evidence identified was mainly from uncontrolled observational studies, making causality difficult to establish. Studies were heterogeneous in methodology and outcome measures. There was a trend toward excess AEs using the RC method, in comparison to the AL and 3DS methods. The methodological quality of the AL studies was low. A direct comparison of AL and 3DS methods would be informative.

Holistic Approach to Complex Cancer Pain

“…However, advocates of RC method argued that RC gives a faster onset of analgesic effect. It is found that time to achieve dose stabilisation with RC is shorter (around 3 days) compared to AL (3-6 days) and 3DS method (3-11 days) [9,11].…”

“…Methadone is also attractive because of its lack of neuro-active metabolites, clearance independent of renal function, good oral bioavailability of approximately 80%, low cost, and long half-life thus fewer doses needed per day [9,10]. However, there is wide interindividual variation in the metabolism of methadone due to genetic polymorphisms in the enzymes responsible for metabolism of methadone, namely the CYP450 3A4, CYP450 2D6 and CYP450 2B6 [11]. This results in variable plasma half-life of methadone, ranging from 13 to 58 hours, causing unpredictable accumulation of methadone in the initial days of treatment.…”

Comparing Methadone Rotation to Consensus Opinion

“…3 However, unlike other opioids, there is no standard method of rotation to methadone or equianalgesic dose conversion ratio, making rotations to methadone challenging and potentially dangerous. 3 Many methods of methadone rotation have been proposed, including rapid conversion or stop-and-go method (i.e., stopping original opioid and starting methadone at full dose), 4 crosstapering or three-day switch (i.e., decreasing the original opioid while increasing methadone), 5,6 and ad libitum (i.e., allowing patients to self-titrate using as-needed methadone), 7 but no single method of rotation has been proven to be superior to others. A systematic review of opioid methadone rotation methods among patients with cancer-related pain identified 25 studies but found insufficient evidence to recommend one method over another.…”

“…A systematic review of opioid methadone rotation methods among patients with cancer-related pain identified 25 studies but found insufficient evidence to recommend one method over another. 3 Successful rotation to methadone (as defined by a statistically or a clinically significant reduction in pain and/or adverse events) occurred among 72%e93% of patients in the studies, depending on the method and outcome definition. 3 Notably, there have been no comparative effectiveness studies comparing rotation methods to one another.…”

“…3 Successful rotation to methadone (as defined by a statistically or a clinically significant reduction in pain and/or adverse events) occurred among 72%e93% of patients in the studies, depending on the method and outcome definition. 3 Notably, there have been no comparative effectiveness studies comparing rotation methods to one another. Given this gap in the literature, clinicians are left with little evidence to guide their methadone rotation practice.…”