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

Context: Up to 44% of patients with cancer-related pain require opioid rotation (OR) because of inadequate analgesia or side effects. No consensus exists regarding the most efficacious method for rotation to methadone.

Objectives: To define the available evidence regarding methods of rotation to methadone and to determine if sufficient evidence exists regarding the superiority of one method.

Methods: A predefined search strategy, using Medical Subject Headings (MeSH) search terms and keywords combined using Boolean operators, was performed. Study selection was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Data were extracted, quality of studies assessed, and narrative synthesis undertaken.

Results: A total of 3214 potentially relevant studies were identified. Twenty-five studies were included: 15 retrospective and 10 prospective (n = 1229). One trial compared three-day switch (3DS) and rapid conversion (RC) methods; two, 3DS; 10, RC; nine, ad libitum (AL). Success rates were as follows: 3DS-93%, RC-71.7%, and AL-92.8%. The single clinical trial and retrospective studies demonstrated poorer analgesia and an excess of adverse events (AEs) in the RC group (five dropouts because of AEs) compared with the 3DS group (no severe AEs). Time to stable analgesia was as follows: RC <4.3 days and AL <6 days.

Conclusion: 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.