Exceeding the guideline-recommended maximum daily dose of opioids for long-term treatment of non-cancer pain in Germany - a large retrospective observational study.
Guideline
Long-term opioid treatment
Maximum daily doses
Non-cancer pain
Opioid analgesics
Social insurance data
Journal
BMC public health
ISSN: 1471-2458
Titre abrégé: BMC Public Health
Pays: England
ID NLM: 100968562
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
24
04
2024
accepted:
19
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
High-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data. The retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time. The sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time. The results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal. German Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.
Sections du résumé
BACKGROUND
BACKGROUND
High-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data.
METHODS
METHODS
The retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time.
RESULTS
RESULTS
The sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time.
CONCLUSIONS
CONCLUSIONS
The results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal.
TRIAL REGISTRATION
BACKGROUND
German Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.
Identifiants
pubmed: 39334000
doi: 10.1186/s12889-024-20141-4
pii: 10.1186/s12889-024-20141-4
doi:
Substances chimiques
Analgesics, Opioid
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2580Informations de copyright
© 2024. The Author(s).
Références
Häuser W, Bock F, Hüppe M, Nothacker M, Norda H, Radbruch L, Schiltenwolf M, Schuler M, Tölle T, Viniol A, Petzke F; Koautoren für die Konsensusgruppe der 2. Aktualisierung der S3-Leitlinie LONTS. Empfehlungen der zweiten Aktualisierung der Leitlinie LONTS : Langzeitanwendung von Opioiden bei chronischen nicht-tumorbedingten Schmerzen [Recommendations of the second update of the LONTS guidelines : Long-term opioid therapy for chronic noncancer pain]. Schmerz. 2020;34(3):204–244. German. https://doi.org/10.1007/s00482-020-00472-y . Erratum in: Schmerz. 2021 Feb;35(1):59–60.
Häuser W, Schubert T, Scherbaum N, Tölle T. Guideline-recommended vs high-dose long-term opioid therapy for chronic noncancer pain is associated with better health outcomes: data from a representative sample of the German population. Pain. 2018;159(1):85–91.
doi: 10.1097/j.pain.0000000000001067
pubmed: 28953194
Schubert I, Ihle P, Sabatowski R. Increase in opiate prescription in Germany between 2000 and 2010: a study based on insurance data. Dtsch Arztebl Int. 2013;110(4):45–51.
pubmed: 23413387
pmcid: 3570953
Verthein U, Buth S, Daubmann A, Martens M-S, Schulte B. Trends in risky prescriptions of opioid analgesics from 2011 to 2015 in Northern Germany. J Psychopharmacol. 2020;34(11):1210–7.
doi: 10.1177/0269881120936544
pubmed: 32674662
pmcid: 7605054
Werber A, Marschall U, L’Hoest H, Hauser W, Moradi B, Schiltenwolf M. Opioid therapy in the treatment of chronic pain conditions in Germany. Pain Physician. 2015;18(3):E323–31.
doi: 10.36076/ppj/2015.18.E323
pubmed: 26000679
Ludwig W-D, Mühlbauer B, Seifert R. Erratum zu: Arzneiverordnungs-Report 2022. In: Ludwig W-D, Mühlbauer B, Seifert R, editors. Arzneiverordnungs-Report 2022. Berlin, Heidelberg: Springer, Berlin Heidelberg; 2023. p. E1–2.
Rosner B, Neicun J, Yang JC, Roman-Urrestarazu A. Opioid prescription patterns in Germany and the global opioid epidemic: Systematic review of available evidence. PLoS ONE. 2019;14(8):e0221153.
doi: 10.1371/journal.pone.0221153
pubmed: 31461466
pmcid: 6713321
Seitz NN, Lochbühler K, Atzendorf J, Rauschert C, Pfeiffer-Gerschel T, Kraus L. Trends In Substance Use And Related Disorders: Analysis of the Epidemiological Survey of Substance Abuse 1995 to 2018. Dtsch Arztebl Int. 2019;116(35–36):585–91.
pubmed: 31587706
pmcid: 6804271
Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte). Federal Opium Agency – Ensuring supply. Preventing abuse. 2024. https://www.bfarm.de/EN/Federal-Opium-Agency/_node.html . Accessed 20 July 2023.
Quinn PD, Chang Z, Pujol TA, Bair MJ, Gibbons RD, Kroenke K, et al. Association between prescribed opioid dose and risk of motor vehicle crashes. Pain. 2022;164(4):e228–36.
doi: 10.1097/j.pain.0000000000002790
pubmed: 36155384
pmcid: 11104685
Olesen SS, Poulsen JL, Broberg MC, Madzak A, Drewes AM. Opioid treatment and hypoalbuminemia are associated with increased hospitalisation rates in chronic pancreatitis outpatients. Pancreatology. 2016;16(5):807–13.
doi: 10.1016/j.pan.2016.06.004
pubmed: 27320721
Garg RK, Fulton-Kehoe D, Franklin GM. Patterns of Opioid Use and Risk of Opioid Overdose Death Among Medicaid Patients. Med Care. 2017;55(7):661–8.
doi: 10.1097/MLR.0000000000000738
pubmed: 28614178
Mercadante S, Arcuri E, Santoni A. Opioid-Induced Tolerance and Hyperalgesia. CNS Drugs. 2019;33(10):943–55.
doi: 10.1007/s40263-019-00660-0
pubmed: 31578704
Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ. Efficacy, Tolerability, and Dose-Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta-analysis. JAMA Intern Med. 2016;176(7):958–68.
doi: 10.1001/jamainternmed.2016.1251
pubmed: 27213267
Els C, Jackson TD, Hagtvedt R, Kunyk D, Sonnenberg B, Lappi VG, et al. High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2023;3(3):Cd012299.
pubmed: 36961252
Marschall U, L’Hoest H, Radbruch L, Häuser W. Long-term opioid therapy for chronic non-cancer pain in Germany. Eur J Pain. 2016;20(5):767–76.
doi: 10.1002/ejp.802
pubmed: 26492066
Häuser W, Schubert T, Scherbaum N, Tölle T. Long-term opioid therapy of non-cancer pain : Prevalence and predictors of hospitalization in the event of possible misuse. Schmerz. 2018;32(6):419–26.
doi: 10.1007/s00482-018-0324-4
pubmed: 30242530
Grunenthal GmbH/Seqirus. Tramal® 50 – 100 mg data sheet 2022. Available from: https://www.medsafe.govt.nz/profs/datasheet/t/TramalcapSRtabinjoraldrops.pdf .
Lang P, Irnich D. Chapter 25 - Systemic pharmacotherapy. In: Irnich D, editor. Myofascial Trigger Points. Oxford: Churchill Livingstone; 2013. p. 253–9.
doi: 10.1016/B978-0-7020-4312-3.00025-8
Häuser W, Maier C, Petzke F, Radbruch L, Sabatowski R. Opioidrotation (LONTS - Praxiswerkzeug 10). AWMF. 2020. https://www.schmerzgesellschaft.de/fileadmin/pdf/LONTS_Praxiswerkzeug_09.pdf . Accessed 15 April 2022.
DAK-Gesundheit. Zahlen & Fakten - Geschäftsbericht 2018 (Numbers & facts - business report 2018) 2018. Available from: https://www.dak.de/dak/download/geschaeftsbericht-2018-2142862.pdf .
Schrader NF, Niemann A, Speckemeier C, Abels C, Blase N, Giebel GD, et al. Prescription of opioid analgesics for non-cancer pain in Germany: study protocol for a mixed methods analysis. Journal of Public Health. 2022.
WIdO - Wissenschaftliches Institut der AOK. Arzneimittel-Stammdatei. 2022. https://www.wido.de/publikationen-produkte/arzneimittel-klassifikation/arzneimittel-stammdatei/?L=0 . Accessed 15 May 2022.
Fricke U, Günther J, Niepraschk-von Dollen K, Zawinell A. Anatomisch-therapeutisch-chemische Klassifikation mit Tagesdosen für den deutschen Arzneimittelmarkt. WIdO - Wissenschaftliches Institut der AOK. 2018. https://www.wido.de/fileadmin/Dateien/Dokumente/Publikationen_Produkte/Arzneimittel-Klassifikation/wido_arz_atc_gkv-ai_2018.pdf . Accessed 16 May 2022.
Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetics (FPM, ANZCA). Opioid Dose Equivalence Calculation Table. 2021. https://www.anzca.edu.au/getattachment/6892fb13-47fc-446b-a7a2-11cdfe1c9902/PS01(PM)-(Appendix)-Opioid-Dose-Equivalence-Calculation-Table . Accessed 3 May 2022.
Treillet E, Laurent S, Hadjiat Y. Practical management of opioid rotation and equianalgesia. J Pain Res. 2018;11:2587–601.
doi: 10.2147/JPR.S170269
pubmed: 30464578
pmcid: 6211309
U.S. Department of Health & Human Services. Opioid Oral Morphine Milligram Equivalent (MME) Conversion Factors. 2020. https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/Opioid%20Morphine%20EQ%20Conversion%20Factors%20%28vFeb%202018%29.pdf . Accessed 3 May 2022.
Cuschieri RJ, Morran CG, McArdle CS. Comparison of morphine and sublingual buprenorphine following abdominal surgery. Br J Anaesth. 1984;56(8):855–9.
doi: 10.1093/bja/56.8.855
pubmed: 6430310
Universitätsspital Basel. Umrechnungsfaktoren zur Opioidrotation 2016. Available from: https://www.spitalpharmazie-basel.ch/dienstleistungen/opioide.php .
Verordnung über das Verschreiben, die Abgabe und den Nachweis des Verbleibs von Betäubungsmitteln - Betäubungsmittel-Verschreibungsverordnung [BtMVV] [Narcotic Drugs Prescription Order]. 1998. BGBl. I at 74, § 8. https://www.gesetze-im-internet.de/btmvv_1998/BtMVV.pdf . (Ger).
Gesetz über den Verkehr mit Betäubungsmitteln – Betäubungsmittelgesetz [BtMG] [Narcotic Drugs Act]. 1994. BGBl I at 358, annex III. https://www.gesetze-im-internet.de/btmg_1981/BtMG.pdf . (Ger).
Schofield J, Steven D, Foster R, Matheson C, Baldacchino A, McAuley A, et al. Quantifying prescribed high dose opioids in the community and risk of overdose. BMC Public Health. 2021;21(1):1174.
doi: 10.1186/s12889-021-11162-4
pubmed: 34162361
pmcid: 8223343
Zin CS, Chen LC, Knaggs RD. Changes in trends and pattern of strong opioid prescribing in primary care. Eur J Pain. 2014;18(9):1343–51.
doi: 10.1002/j.1532-2149.2014.496.x
pubmed: 24756859
pmcid: 4238849
Boudreau D, Von Korff M, Rutter CM, Saunders K, Ray GT, Sullivan MD, et al. Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol Drug Saf. 2009;18(12):1166–75.
doi: 10.1002/pds.1833
pubmed: 19718704
pmcid: 3280087
Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Sullivan MD, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152(2):85–92.
doi: 10.7326/0003-4819-152-2-201001190-00006
pubmed: 20083827
pmcid: 3000551
Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686–91.
doi: 10.1001/archinternmed.2011.117
pubmed: 21482846
Gomes T, Redelmeier DA, Juurlink DN, Dhalla IA, Camacho X, Mamdani MM. Opioid dose and risk of road trauma in Canada: a population-based study. JAMA Intern Med. 2013;173(3):196–201.
doi: 10.1001/2013.jamainternmed.733
pubmed: 23318919
Moisset X, Trouvin AP, Tran VT, Authier N, Vergne-Salle P, Piano V, et al. Use of strong opioids in chronic non-cancer pain in adults. Evidence-based recommendations from the French Society for the Study and Treatment of Pain. Presse Med. 2016;45(4 Pt 1):447–62.
doi: 10.1016/j.lpm.2016.02.014
pubmed: 27067628
Busse JW, Craigie S, Juurlink DN, Buckley DN, Wang L, Couban RJ, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ. 2017;189(18):E659–66.
doi: 10.1503/cmaj.170363
pubmed: 28483845
pmcid: 5422149
Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep. 2022;71(3):1–95.
doi: 10.15585/mmwr.rr7103a1
pubmed: 36327391
pmcid: 9639433
Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276–86.
doi: 10.7326/M14-2559
pubmed: 25581257
Hoffmann F, Glaeske G, Windt R. Verordnung von starken Opioiden im Jahr 2011. Der Schmerz. 2012;26(6):707–14.
doi: 10.1007/s00482-012-1240-7
pubmed: 23183991
Chevalier P, Smulders M, Chavoshi S, Sostek M, LoCasale R. A description of clinical characteristics and treatment patterns observed within prescribed opioid users in Germany and the UK. Pain Management. 2014;4(4):267–76.
doi: 10.2217/pmt.14.26
pubmed: 25300384
Moss C, Bossano C, Patel S, Powell A, Chan Seay R, Borahay MA. Weaning From Long-term Opioid Therapy. Clin Obstet Gynecol. 2019;62(1):98–109.
doi: 10.1097/GRF.0000000000000425
pubmed: 30601171
Jurlink DN. Rethinking “doing well” on chronic opioid therapy. CMAJ. 2017;189(39):E1222-e3.
doi: 10.1503/cmaj.170628
D’Souza G, Wren AA, Almgren C, Ross AC, Marshall A, Golianu B. Pharmacological Strategies for Decreasing Opioid Therapy and Management of Side Effects from Chronic Use. Children. 2018;5(12):163.
doi: 10.3390/children5120163
pubmed: 30563157
pmcid: 6306833
Chang HY, Murimi IB, Jones CM, Alexander GC. Relationship between high-risk patients receiving prescription opioids and high-volume opioid prescribers. Addiction. 2018;113(4):677–86.
doi: 10.1111/add.14068
pubmed: 29193546
Stein JD, Lum F, Lee PP, Rich WL 3rd, Coleman AL. Use of health care claims data to study patients with ophthalmologic conditions. Ophthalmology. 2014;121(5):1134–41.
doi: 10.1016/j.ophtha.2013.11.038
pubmed: 24433971
Neubauer S, Kreis K, Klora M, Zeidler J. Access, use, and challenges of claims data analyses in Germany. Eur J Health Econ. 2017;18(5):533–6.
doi: 10.1007/s10198-016-0849-3
pubmed: 27878393
Bruera E, Pereira J, Watanabe S, Belzile M, Kuehn N, Hanson J. Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer. 1996;78(4):852–7.
doi: 10.1002/(SICI)1097-0142(19960815)78:4<852::AID-CNCR23>3.0.CO;2-T
pubmed: 8756381
Lawlor P, Turner K, Hanson J, Bruera E. Dose ratio between morphine and hydromorphone in patients with cancer pain: a retrospective study. Pain. 1997;72(1–2):79–85.
doi: 10.1016/S0304-3959(97)00018-3
pubmed: 9272790