Letter to the Editor - Authors’ reply to the letter to the editor regarding “Low-dose naltrexone for fibromyalgia: a re-analysis suggests lower efficacy than previously reported”

Sep 29, 2026

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Authors respond to comments on a previously published systematic review and meta-analysis assessing efficacy and safety of low-dose naltrexone for fibromyalgia in the Korean Journal of Pain. The correspondence addresses a data extraction oversight for the outcome “at least 30% improvement in pain symptoms,” clarifying that Table 2 included participants achieving ≥30% improvement including those with 50%. Authors also explain the choice of effect size using mean difference rather than standardized mean difference due to scale comparability and heterogeneity behavior, and discuss data-handling across included trials.

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TO THE EDITOR

Clarification on “at least 30% improvement in pain symptoms”

Rationale for mean difference vs standardized mean difference

Handling of data from included studies

Korean J Pain 2026;39(1):144-146 [https://doi.org/10.3344/kjp.25362](https://doi.org/10.3344/kjp.25362)[ ](https://doi.org/10.3344/kjp.25362)[pISSN 2005-9159](pISSN 2005-9159), eISSN 2093-0569 |
Letter to the Editor
Authors’ reply to the letter to the editor regarding“Low-dose naltrexone for fibromyalgia: a
re-analysis suggests lower efficacy than previously reported”
Timotius Ivan Hariyanto1, Akhil Deepak Vatvani1, Pratik Patel2, and Theo Audi Yanto3
1 Department of Medicine, Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang, Indonesia 2 Department of Medicine, Washington University of Health and Science, Belize, Central America, USA 3 Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang, Indonesia | | | --- | --- | | Received October 13, 2025; Accepted October 17, 2025 Handling Editor: Hyun Kang
Correspondence: Timotius Ivan Hariyanto
Department of Medicine, Faculty of Medicine, Pelita Harapan University, Boulevard Jendral Sudirman street, Karawaci, Tangerang 15811, Indonesia
Tel: +6281288762391, E-mail: [timotius.hariyanto95@gmail.com](timotius.hariyanto95@gmail.com) | | | TO THE EDITOR
We sincerely appreciate the interest in our recently published article entitled “Efficacy and safety of low-dose naltrexone for the management offibromyalgia: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis,” in the Korean Journal of Pain [1] . We would like to thank Dr. Due Bruun and colleagues for their careful review and constructive feedback [2], and we appreciate the opportunity to respond to their thoughtful comments and clarify the points raised in this correspondence.
We appreciate the opportunity to clarify the issue regarding the outcome of “at least 30% improvement in pain symptoms.” We acknowledge an oversight in data extraction from the study by Due Bruun et al. [3] . The error arose because the extraction was based solely on the information presented in Table 2, which reported “30% improvement in pain.” This was initially interpreted as referring exclusively to participants who achieved a 30% | improvement, without including those who experienceda 50% improvement. Upon careful re-examination, and as correctly noted in the letter, the text of the original article indicates that the data presented under “30% improvement in pain” in Table 2 actually encompassed participants who achieved at least 30% improvement—including those with 50% improvement [3] . We sincerely regret this oversight in data interpretation. Nevertheless, this minor correction does not alter the overall conclusions of our meta-analysis, as low-dose naltrexone remains associated with a significantly greater proportion of patients achieving ≥ 30% improvement in pain compared with placebo among individuals with fibromyalgia, consistent
with the findings highlighted in the correspondence.
We also appreciate the concern raised regarding the potential overestimation of the “Changes in Pain Scores”outcome. The letter suggested that standardized mean difference (SMD) should have been used to pool the effect estimates due to presumed differences in the reporting scales. However, we respectfully disagree with | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by-nc/4.0](licenses/by-nc/4.0)), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © The Korean Pain Society this interpretation. Among the four studies included, only one (Bested et al. [4]) clearly used a different pain measurement scale. The study by Paula et al. [5] utilizeda Visual Analog Scale (VAS) with a 0–10 range, while the study by Due Bruun et al. [3] employed a Numeric Ratin

FAQs

What was the main data interpretation oversight addressed by the authors?

The authors acknowledged an error in data extraction for the outcome “30% improvement in pain,” which was initially treated as exactly 30% achievers. Re-examination showed Table 2 included participants with at least 30% improvement, including those who achieved 50%.

Why did the authors use mean difference instead of standardized mean difference (SMD)?

They pre-specified mean difference to keep outcomes in natural units and improve clinical interpretability. They also argued SMD produced greater heterogeneity because SMD depends on within-study standard deviations, which are less stable in smaller studies.

Did the authors consider the correction to change the overall conclusions?

The authors stated the correction was minor and did not alter the meta-analysis overall conclusions, maintaining that low-dose naltrexone was associated with a significantly greater proportion of patients achieving ≥30% pain improvement versus placebo.

Sep 29, 2026

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