Impact of treatment duration on the effectiveness of opioid analgesia: a systematic review and meta-analysis

Liesbeth S Froentjes; Catherine AM Barrington; Rodger A Craig; Mareiz Morcos; Dawn M Wedman; Christina S Korowynk; Michael D Kelmer; Farah N Campbell; Scott R Garrison

doi:10.3399/BJGP.2025.0705

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Treatment duration and opioid analgesia: caution in interpretation
Saba Aghajani, Chris G. Maher and Gustavo C. Machado

Published on: 16 August 2026

Published on: (16 August 2026)
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Treatment duration and opioid analgesia: caution in interpretation
Saba Aghajani, PhD student, Institute for Musculoskeletal Health, Sydney Local Health District, Sydney, NSW Australia
Other Contributors:
Chris G. Maher, Professor, Institute for Musculoskeletal Health, Sydney Local Health District, Sydney, NSW Australia

Gustavo C. Machado, Associate Professor, Institute for Musculoskeletal Health, Sydney Local Health District, Sydney, NSW Australia
We read with interest the systematic review by Froentjes and colleagues examining whether opioid effectiveness diminishes with treatment duration.¹We believe, however, that the conclusion regarding loss of effectiveness over time may not be fully supported by the reported analyses.

The apparent effect of treatment duration should be interpreted with caution because it arises from comparison of groups of trials defined by different treatment durations. While treatment allocation was randomised within individual trials, the duration of the treatment was not. Consequently, comparisons across duration categories are observational and so confounding is a concern. The borderline subgroup difference (p=0.05) could reflect differences in patient populations, opioid type or dose, comparators, outcome definitions, and other trial characteristics rather than an effect of treatment duration itself.

The main conclusion also relies heavily on the responder analysis where continuous pain outcomes were dichotomised. However, the analysis using continuous pain measures found no significant differences across treatment durations (p=0.22). This analysis included substantially more evidence than the responder analysis and was also supported by higher GRADE certainty. Moreover, it avoids the problems associated with dichotomising continuous outcomes. Converting continuous pain scores into responder categories results in loss of information, reduces statistical...
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We read with interest the systematic review by Froentjes and colleagues examining whether opioid effectiveness diminishes with treatment duration.¹We believe, however, that the conclusion regarding loss of effectiveness over time may not be fully supported by the reported analyses.

The apparent effect of treatment duration should be interpreted with caution because it arises from comparison of groups of trials defined by different treatment durations. While treatment allocation was randomised within individual trials, the duration of the treatment was not. Consequently, comparisons across duration categories are observational and so confounding is a concern. The borderline subgroup difference (p=0.05) could reflect differences in patient populations, opioid type or dose, comparators, outcome definitions, and other trial characteristics rather than an effect of treatment duration itself.

The main conclusion also relies heavily on the responder analysis where continuous pain outcomes were dichotomised. However, the analysis using continuous pain measures found no significant differences across treatment durations (p=0.22). This analysis included substantially more evidence than the responder analysis and was also supported by higher GRADE certainty. Moreover, it avoids the problems associated with dichotomising continuous outcomes. Converting continuous pain scores into responder categories results in loss of information, reduces statistical power, and may underestimate the extent of variation between groups or obscure the underlying relationship.²

The conclusion that opioid effectiveness declines with treatment duration is only supported by the smaller, dichotomised analysis, while the larger and higher certainty analysis of continuous pain outcomes does not show the same pattern. Neither analysis adjusted for confounding. We therefore suggest a more cautious interpretation of the results.

References
1. Froentjes LS, Barrington CAM, Craig RA et al. Impact of treatment duration on the effectiveness of opioid analgesia: a systematic review and meta-analysis. Br J Gen Pract 2026;76(769):e634.
2. Altman DG, Royston P. The cost of dichotomising continuous variables. BMJ 2006;332(7549):1080.

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Competing Interests: None declared.

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