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Cited by 40Fibromyalgia and Chronic Fatigue Syndrome ResearchMusculoskeletal pain and rehabilitationPain Mechanisms and Treatments

Duloxetine for fibromyalgia syndrome: a systematic review and meta-analysis

Open access
Migliorini, Filippo, Maffulli, Nicola, Eschweiler, Jörg, Baroncini, Alice, Bell, Andreas, Colarossi, Giorgia·2023·Journal of Orthopaedic Surgery and Research
DOI 10.1186/s13018-023-03995-zPMC PMC10351165
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Abstract

Introduction: The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated. Material and methods: This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered. Results: Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m 2 . 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30–60, 120 mg/daily, and placebo groups, while the 60–120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30–60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60–120 group, followed by the 30–60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed. Conclusions: Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.

AI snapshot

Written from the paper’s full text.

TL;DR

In this PRISMA systematic review and meta-analysis of 11 double-blind RCTs (3432 patients), duloxetine was superior to placebo for fibromyalgia across FIQ, CGI severity, and BPI pain outcomes regardless of dose. The optimal dose remains uncertain; 60 mg/daily showed the greatest FIQ improvement, while 60–120 mg/daily had the worst FIQ result and some non-clinically relevant BPI changes.

Key findings

  • Data from 3432 patients (11 RCTs) were included; mean age was 46.4 ± 10.7 years, mean BMI 25.3 ± 3.2 kg/m², and 90% (3089/3432) were women.
  • Duloxetine was superior to placebo in all comparisons irrespective of dose: FIQ MD 4.94 (95% CI 3.16–6.72; P = 0.0001), CGI severity MD 0.28 (95% CI 0.13–0.42; P < 0.0001), BPI average pain severity MD 0.77 (95% CI 0.53–1.01; P < 0.0001), and BPI pain interference MD 0.67 (95% CI 0.48–0.86; P < 0.0001).
  • FIQ total improvement was greatest for 60 mg/daily (−15.1 ± 3.0), followed by 30 mg/daily (−14.8 ± 1.4), 30–60 mg/daily (−14.8 ± 1.9), 120 mg/daily (−14.7 ± 1.8), and placebo (−9.3 ± 2.5); 60–120 mg/daily had the worst result (−8.0 ± 1.4). CGI severity showed the lowest improvement with placebo, with no differences among other groups; BPI interference and average pain severity were worst in the 30–60 mg/daily group along with placebo.
  • Placebo had the lowest adverse-event rate (47%, 573/1219; P < 0.0001). Discontinuation rates were lowest in the 60–120 mg/daily group (5%, 32/605), followed by 30–60 mg/daily (6%, 5/91) and 30 mg/daily (9%, 14/155); 120 mg/daily had the highest rate (33%, 73/220).

Methods

  • This study followed 2020 PRISMA and Cochrane recommendations; the search was performed in December 2022 in PubMed, Google Scholar, Embase, Web of Science, and Scopus. Included studies were double-blind placebo-controlled RCTs (level I) of daily duloxetine for fibromyalgia, with a stated daily dose, at least 10 patients, at least 4 weeks follow-up, and quantitative data for outcomes of interest; combined pharmacological and non-pharmacological management studies were excluded.
  • Outcomes were FIQ, BPI pain interference and average pain severity, CGI severity, adverse events, and adverse events leading to discontinuation. MCID was set at 14% improvement for FIQ and 2.1 points (32.3% from baseline) for BPI average pain severity.
  • Analysis used STATA MP version 16 for ANOVA and Tukey’s HSD, and Review Manager version 5.3 for meta-analysis with inverse-variance mean difference; heterogeneity was assessed with Higgins-I² and χ² tests, with fixed- or random-effects models as indicated; funnel plots and Egger’s test assessed publication bias.

Limitations

  • Stated by the paper: only 11 RCTs were eligible, and only two directly compared different duloxetine doses; quantitative CGI-Severity data for 30 mg/daily could not be analyzed; all included studies used the original FIQ rather than the revised FIQR; most studies used flexible doses (30–60 or 60–120 mg/daily), potentially concealing dose-specific effects and biasing adverse-event estimates; starting dose, escalation/adjustment, and washout were not analyzed; no validated MCID was found for BPI pain interference or CGI-Severity; one study was in a pediatric population; follow-up was limited; no pilot tests or inter-rater reliability assessment were performed; and some improvements (FIQ in 60–120 mg/daily; BPI average pain severity in 30–60 and 60–120 mg/daily) were not clinically relevant.
  • Evident from the text: Table 3 reports impossible adverse-event rates above 100% (30–60 mg/daily 124%, 120 mg/daily 176%) and denominators inconsistent with Table 2/Table 1, suggesting data-reporting or calculation errors. The statistical analysis section also states “Values of P > 0.05 were considered statistically significant,” which conflicts with standard convention and the reported P values.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s13018-023-03995-z

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

6 of 17 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    The 30-60 mg/daily group and the placebo group reported the worst BPI interference and average pain severity scores.

    “Concerning the BPI interference and severity pain scores, the 30–60 mg/daily group reported the worst result, along with the placebo group.”
    • Also stated in: § Outcomes of interest · plain
      “Concerning the BPI interference and average severity pain scores, the 30–60 mg/daily group reported the worse result, along with the placebo group.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Placebo resulted in the lowest improvement on the CGI severity scale.

    “Concerning the CGI severity scale, placebo resulted in the lowest improvement”
    • Also stated in: § Outcomes of interest · plain
      “Concerning the CGI severity scale, placebo achieved the lowest improvement”
    Quote in the paperNot a substantial claim
  • Findingown data

    The 60-120 mg/daily group achieved the worst FIQ results.

    “while the 60–120 mg /daily group performed the worst results.”
    • Also stated in: § Outcomes of interest · plain
      “while the 60–120 mg /daily group achieved the worst results.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The 60 mg/daily cohort reported the highest FIQ improvement, followed by the 30, 30-60, 120 mg/daily, and placebo groups.

    “The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30–60, 120 mg/daily, and placebo groups”
    • Also stated in: § Outcomes of interest · plain
      “The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30–60, 120 mg/daily, and placebo groups”
    Quote in the paperNot a substantial claim
  • Findingown data

    Duloxetine improved BPI average pain severity compared with placebo (MD 0.77; 95% CI 0.53, 1.01; P < 0.0001).

    “BPI average pain severity (MD 0.77; 95% CI 0.53, 1.01; P < 0.0001)”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 13
  • May combine two claims. 11

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    This systematic review was conducted according to the PRISMA 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.

    “This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [26] and the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions [27].”
    • Also stated in: § Material and methods · plain
      “This study followed the 2020 PRISMA guidelines.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [26] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hrobjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71. source

      The Abstract identifies this paper as the PRISMA 2020 reporting guideline, supporting citation [26] as the guideline being referenced. The Scope of the guideline section says PRISMA 2020 is not intended to guide systematic review conduct, though it can be useful during planning and conduct. The source therefore does not establish that the citing review was conducted according to PRISMA; the separately cited Cochrane Handbook is outside this verdict. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [27] Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions version 6.2. Cochrane 2021. Available from www.training.cochrane.org/handbook. Accessed on February 2022.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Which dose of duloxetine is optimal for fibromyalgia remains controversial.

    “however, which dose is optimal for fibromyalgia remains controversial.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [11] Arnold LM, Lu Y, Crofford LJ, Wohlreich M, Detke MJ, Iyengar S, Goldstein DJ. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum. 2004;50(9):2974–84. https://doi.org/10.1002/art.20485. source
    • cites [23] Mohs R, Mease P, Arnold LM, Wang F, Ahl J, Gaynor PJ, Wohlreich MM. The effect of duloxetine treatment on cognition in patients with fibromyalgia. Psychosom Med. 2012;74(6):628–34. https://doi.org/10.1097/PSY.0b013e31825b9855. source
    • cites [24] Murakami M, Osada K, Mizuno H, Ochiai T, Alev L, Nishioka K. A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese fibromyalgia patients. Arthritis Res Ther. 2015;17:224. https://doi.org/10.1186/s13075-015-0718-y. source

      The Methods (Study design; page unavailable) describe titration to 60 mg, and the Discussion (Analgesic effect of duloxetine on fibromyalgia; page unavailable) notes that once-daily 60 mg was approved in other countries. Neither passage addresses whether the optimal dose is controversial; searches for optimal dosage and comparisons among doses found no such statement in our copy. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [25] Russell JI, Mease PJ, Smith TR, Kajdasz DK, Wohlreich MM, Detke MJ, Walker DJ, Chappell AS, Arnold LM. Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial. Pain. 2008;136(3):432–44. https://doi.org/10.1016/j.pain.2008.02.024. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    One included study was conducted on a pediatric population.

    “One included study [37] was conducted on a pediatric population.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [37] Upadhyaya HP, Arnold LM, Alaka K, Qiao M, Williams D, Mehta R. Efficacy and safety of duloxetine versus placebo in adolescents with juvenile fibromyalgia: results from a randomized controlled trial. Pediatr Rheumatol Online J. 2019;17(1):27. https://doi.org/10.1186/s12969-019-0325-6. source

  • May combine two claims.

    Findingcitation

    All included studies referred to the original version of the FIQ score; the revised version was not used.

    “All the included studies referred to the original version of the FIQ score [46]: the revised version of the FIQ was not used [47].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [46] Burckhardt CS, Clark SR, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol. 1991;18(5):728–33.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [47] Bennett RM, Friend R, Jones KD, Ward R, Han BK, Ross RL. The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties. Arthritis Res Ther. 2009;11(4):R120. https://doi.org/10.1186/ar2783. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Duloxetine is an antidepressant belonging to the serotonin and noradrenalin reuptake inhibitors (SNRIs).

    “Duloxetine is an antidepressant which belongs to the category of the serotonin and noradrenalin reuptake inhibitors (SNRIs) [22].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014. https://doi.org/10.1002/14651858.CD007115.pub3. source

  • Classified as probably not a substantial claim.

    Premisecitation

    The minimal clinically important difference (MCID) for the FIQ is 14% improvement.

    “The minimal clinically important difference (MCID) for the FIQ was set as the 14% improvement [29].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Bennett RM, Bushmakin AG, Cappelleri JC, Zlateva G, Sadosky AB. Minimal clinically important difference in the fibromyalgia impact questionnaire. J Rheumatol. 2009;36(6):1304–11. https://doi.org/10.3899/jrheum.081090. source

  • May combine two claims.

    Findingown data

    Duloxetine was superior to placebo in all comparisons, irrespective of dose, in all endpoints analysed.

    “Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed.”
    • Also stated in: § Meta-analyses · plain
      “Duloxetine was superior in all the comparisons to placebo irrespective of the doses: FIQ (MD 4.94; 95% CI 3.16, 6.72; P = 0.0001), CGI severity scale (MD 0.28; 95% CI 0.13, 0.42; P < 0.0001), BPI average pain severity (MD 0.77; 95% CI 0.53, 1.01; P < 0.0001), BPI pain interference (MD 0.67; 95% CI 0.48, 0.86; P < 0.0001).”
    • Also stated in: § Conclusions · plain
      “Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    The starting dose could not be analysed.

    “The starting dose could not be to analysed”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Although duloxetine statistically improved the investigated PROMs, the changes of FIQ in the 60-120 mg/daily group and of BPI-average pain severity subscale in the 30-60 mg and 60-120 mg/daily groups were not clinically relevant.

    “Although the administration of duloxetine statistically improved the investigated PROMs, the changes of FIQ in 60–120 mg/daily group and of BPI-average pain severity subscale in 30–60 mg and 60–120 mg/daily groups were not clinically relevant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    No validated MCID was found for BPI pain interference subscale and CGI-Severity scale.

    “No validated MCID was found for BPI pain interference subscale and CGI-Severity scale.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingnone given

    The study was not able to determine the recommended dose of duloxetine.

    “Unfortunately, we were not able to determine the recommended dose of duloxetine.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    It was not possible to include for analysis the CGI-Severity scale concerning the 30 mg/daily administration due to lack of quantitative data.

    “Given the lack of quantitative data, it was not possible to include for analysis the CGI-Severity scale concerning the 30 mg/daily administration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Flexible doses of duloxetine may conceal the real potential of one dose over another, increasing the risk of biased conclusions.

    “this may conceal the real potential of one dose over another, increasing the risk of biased conclusions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Pilot tests before starting data extraction were not performed.

    “Pilot tests before starting data extraction were not performed”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Flexible doses of duloxetine may also misrepresent the occurrence of adverse events and impact the results.

    “Flexible doses of duloxetine may also misrepresent the occurrence of adverse events and impact the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Abnormalities in serotonin neurotransmission are involved in major depression disorders, which occur often in patients with fibromyalgia.

    “Moreover, abnormalities in serotonin neurotransmission are also involved in major depression disorders, which occur often in patients with fibromyalgia [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Hudson JI, Pope HG Jr. The relationship between fibromyalgia and major depressive disorder. Rheum Dis Clin North Am. 1996;22(2):285–303. https://doi.org/10.1016/s0889-857x(05)70273-8. source

  • May combine two claims.

    Study design and conductreasoning

    The methodological assessment evidenced a good quality, attesting a low risk of publication bias.

    “Concluding, the methodological assessment evidenced a good quality, attesting a low risk of publication bias”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Inter-rater reliability in data extraction has not been evaluated.

    “and inter-rater reliability in data extraction has not been evaluated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The MCID for the BPI average pain severity subscale is 2.1 points, an improvement of 32.3% from baseline.

    “The MCID for the BPI- average pain severity subscale was set at 2.1 points, an improvement of 32.3% from baseline [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Mease PJ, Spaeth M, Clauw DJ, Arnold LM, Bradley LA, Russell IJ, Kajdasz DK, Walker DJ, Chappell AS. Estimation of minimum clinically important difference for pain in fibromyalgia. Arthritis Care Res. 2011;63(6):821–6. https://doi.org/10.1002/acr.20449. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The risk of bias graph tool of the Review Manager Software was used to assess the risk of bias in RCTs.

    “The risk of bias graph tool of the Review Manager Software (Version 5.3; The Nordic Cochrane Collaboration, Copenhagen) was used to assess the risk of bias in RCTs.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The following risk of bias were evaluated: selection, detection, performance, attrition, reporting, and other source of bias.

    “The following risk of bias were evaluated: selection, detection, performance, attrition, reporting, and other source of bias.”
    Quote in the paperNot a substantial claim
21 of 21

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Reported adverse-event rates exceed 100%

    Major

    The methods describe these outcomes as binary event rates, but Table 3 reports rates of 124% and 176%. A binary adverse-event rate over patients cannot exceed 100%.

  • Statistical-significance threshold reverses within the methods

    Minor

    The statistical analysis section first defines P < 0.05 as significant, then says P > 0.05 is significant.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Howick J CI, Glasziou P, Greenhalgh T, Carl Heneghan, Liberati A, Moschetti I, Phillips B, Thornton H, Goddard O, Hodgkinson M. The 2011 Oxford CEBM Levels of Evidence. Oxford Centre for Evidence-Based Medicine. 2011. Available at https://www.cebmnet/index.aspx?o=5653.

Cited by

Still being checked.

Related

Authors
Migliorini, F., Maffulli, N., Eschweiler, J., Baroncini, A., Bell, A., & Colarossi, G.
Affiliations
  • Ospedale di Bolzano (IT)
  • University of Salerno (IT)
  • Universitätsklinikum Aachen (DE)
Corresponding author
Migliorini, Filippo
ORCID
Venue
Journal of Orthopaedic Surgery and Research
Publisher
Springer Science and Business Media LLC
Published
2023-07-17
Volume
18
Issue
1
Pages
504-504
ISSN
1749-799X (ISSN-L)
DOI
10.1186/s13018-023-03995-z
PMC
PMC10351165
OpenAlex
W4384524630
Semantic Scholar
045dff5949dafe5ec7a7c398afa25371b449dc1f
Cited by
40
References
45
Citations by year
2026: 13 · 2025: 10 · 2024: 15 · 2023: 2
FWCI
2.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Orthopaedic Surgery and Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RWTH Publications (RWTH Aachen) (publishedVersion, other-oa)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • RWTH Publications (RWTH Aachen)
Funders
Universitätsklinikum RWTH Aachen
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
duloxetine, fibromyalgia, antidepressant efficacy, adverse events, Fibromyalgia Impact Questionnaire, Brief Pain Inventory, Clinical Global Impression Scale, placebo comparison, individualized dosing
MeSH terms
Duloxetine Hydrochloride, Adult, Female, Fibromyalgia, Humans, Male, Middle Aged, Pain, Thiophenes, Randomized Controlled Trials as Topic, Treatment Outcome

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-22.

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