Evidence of lithium underuse in bipolar disorder: analysis of lithium and antipsychotic consumption, prediction of future trends, regional disparities and indicators of rational and inappropriate use in Europe.

Uložené v:
Podrobná bibliografia
Názov: Evidence of lithium underuse in bipolar disorder: analysis of lithium and antipsychotic consumption, prediction of future trends, regional disparities and indicators of rational and inappropriate use in Europe.
Autori: Bindel LJ; Institute of Pharmacology, Hannover Medical School, 30625, Hannover, Germany., Seifert R; Institute of Pharmacology, Hannover Medical School, 30625, Hannover, Germany. seifert.roland@mh-hannover.de.
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2025 Dec; Vol. 398 (12), pp. 18049-18070. Date of Electronic Publication: 2025 Jun 28.
Spôsob vydávania: Journal Article
Jazyk: English
Informácie o časopise: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE
Imprint Name(s): Original Publication: Berlin, New York, Springer Verlag.
Výrazy zo slovníka MeSH: Bipolar Disorder*/drug therapy , Bipolar Disorder*/epidemiology , Antipsychotic Agents*/therapeutic use , Practice Patterns, Physicians'*/trends , Practice Patterns, Physicians'*/statistics & numerical data , Lithium Compounds*/therapeutic use , Inappropriate Prescribing*/trends , Inappropriate Prescribing*/statistics & numerical data , Antimanic Agents*/therapeutic use, Humans ; Europe/epidemiology ; Drug Utilization/trends ; Healthcare Disparities/trends
Abstrakt: Mental disorders represent a significant global burden. Despite increasing use of medications, there is no evidence that this burden is decreasing. Lithium has been one of the first-line treatments in bipolar disorder for many years. However, lithium prescribing has plateaued, while antipsychotic use increased over the past decades. This study assesses the current situation and historical trends in 11 European countries for lithium and antipsychotic medications, predicts future trends and presents key characteristics for assessing the appropriate or inappropriate use of lithium. Consumption data for lithium (ATC N05AN) and antipsychotics (ATC N05A) were collected from publicly available sources in European countries, spanning from 1997 to 2024. An analysis of past trends in DID (defined daily dose per 1000 population per day) prescriptions for lithium and antipsychotics was performed and predictions were made until 2030, using ARIMA(0,1,0) models. For each country, the lithium treatment coverage for the prevalence of bipolar disorder was calculated, along with the ratio of antipsychotic to lithium use. Identified similarities and differences were compared between countries and between northern and southern European regions to generalise prescribing patterns. Based on these results, the prescribing behaviour of lithium in the analysed countries was classified as good, moderate or poor. Data were available for 11 countries, including Croatia, Denmark, Estonia, Finland, Germany, Iceland, Italy, the Netherlands, Norway, Spain and Sweden. In all countries, lithium consumption plateaued or declined, while antipsychotic use increased. Projections suggest a continuation of observed trends. Treatment coverage was very low, with the highest rate in Sweden (32.6%) and the lowest in Estonia and Croatia (5.3%). Comparably good prescribing behaviour was observed in the Netherlands, Sweden, Denmark and Iceland. Moderate prescribing was observed in Germany, Spain, Finland and Norway, while poor compliance with lithium prescribing was reported in Italy, Croatia and Estonia. Lithium prescribing is influenced by adherence to guidelines, concerns about side effects and practicability, monitoring infrastructure, clinician training and prescribing preferences. However, antipsychotics also come with severe adverse effects, require extensive monitoring and cause higher healthcare costs compared to lithium. Lithium is increasingly being replaced by antipsychotics in the treatment of bipolar disorder, despite a constant recommendation in guidelines. Lithium remains significantly underused in all countries analysed. A clear north-south shift in prescribing behaviour is observed, with a suggested west-east shift. Northern countries show higher lithium consumption and a lower antipsychotic-to-lithium ratio, reflecting greater adherence to guidelines and more rational prescribing. In contrast, southern countries show lower lithium and higher antipsychotic use. Overall, there is little progress in improving prescribing practices. Withholding lithium from eligible patients is both medically and economically irresponsible. To reduce the burden of mental disorders, effective and evidence-based treatment strategies need to be prioritised, which is currently failed.
(© 2025. The Author(s).)
References: Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug;398(8):10691-10717. (PMID: 40029386)
Int J Neuropsychopharmacol. 2013 Sep;16(8):1719-32. (PMID: 23663490)
Lancet. 2012 Feb 25;379(9817):721-8. (PMID: 22265699)
Acta Psychiatr Scand. 2019 Aug;140(2):91-93. (PMID: 31310342)
Arch Gen Psychiatry. 2011 Mar;68(3):241-51. (PMID: 21383262)
Front Psychiatry. 2024 Jul 02;15:1425549. (PMID: 39015883)
CNS Drugs. 2011 Apr;25(4):289-98. (PMID: 21425882)
Int J Bipolar Disord. 2019 Mar 27;7(1):10. (PMID: 30915592)
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):9723-9743. (PMID: 38916833)
Int J Bipolar Disord. 2016 Dec;4(1):27. (PMID: 27900734)
Lancet Reg Health Eur. 2024 Nov 29;48:101135. (PMID: 39811787)
Eur J Public Health. 2018 Apr 1;28(2):224-230. (PMID: 29165586)
Int J Bipolar Disord. 2025 Feb 13;13(1):3. (PMID: 39945975)
Eur Neuropsychopharmacol. 2017 Oct;27(10):1064-1076. (PMID: 28755801)
Nord J Psychiatry. 2009;63(4):285-91. (PMID: 19140076)
Bipolar Disord. 2012 Sep;14(6):654-63. (PMID: 22612720)
Mol Psychiatry. 2022 Jan;27(1):202-211. (PMID: 33859358)
Int J Bipolar Disord. 2024 Nov 28;12(1):40. (PMID: 39609318)
BMJ. 2013 Jun 27;346:f3646. (PMID: 23814104)
Pharmacopsychiatry. 2018 Sep;51(5):194-199. (PMID: 29270949)
J Affect Disord. 2016 Sep 15;202:120-3. (PMID: 27262632)
Lancet Psychiatry. 2022 Feb;9(2):137-150. (PMID: 35026139)
BMC Psychiatry. 2014 Feb 28;14:58. (PMID: 24576061)
Tidsskr Nor Laegeforen. 2009 Apr 30;129(9):855-7. (PMID: 19415083)
J Affect Disord. 2015 Mar 15;174:303-9. (PMID: 25532077)
J Affect Disord. 2009 Jul;116(1-2):152-7. (PMID: 19091424)
J Affect Disord. 2023 Nov 1;340:237-244. (PMID: 37557987)
Psychiatr Serv. 2012 Mar;63(3):202-4. (PMID: 22388526)
Mol Psychiatry. 2024 Aug;29(8):2571-2574. (PMID: 38454078)
Ther Adv Psychopharmacol. 2018 Apr 26;8(9):251-269. (PMID: 30181867)
Trends Psychiatry Psychother. 2013;35(2):99-105. (PMID: 25923299)
Int J Bipolar Disord. 2021 Mar 9;9(1):10. (PMID: 33687600)
J Psychopharmacol. 2018 Oct;32(10):1104-1109. (PMID: 29896998)
Int Rev Psychiatry. 2022 Feb;34(1):6-15. (PMID: 35584016)
Int J Bipolar Disord. 2021 Jun 1;9(1):18. (PMID: 34061259)
Appl Clin Genet. 2014 Feb 12;7:33-42. (PMID: 24683306)
Int J Bipolar Disord. 2023 Aug 26;11(1):30. (PMID: 37633877)
Int J Bipolar Disord. 2023 May 11;11(1):17. (PMID: 37166695)
Psychiatry Res. 2020 Jul;289:112965. (PMID: 32388174)
Transl Psychiatry. 2021 Jul 5;11(1):366. (PMID: 34226487)
Int J Bipolar Disord. 2018 Oct 20;6(1):22. (PMID: 30341458)
J Affect Disord. 2016 May;195:50-6. (PMID: 26859073)
Health Res Policy Syst. 2020 Sep 15;18(1):102. (PMID: 32933555)
J Correct Health Care. 2022 Oct;28(5):325-328. (PMID: 36190495)
Brain Sci. 2024 Jan 20;14(1):. (PMID: 38275522)
Psychol Med. 2021 Oct;51(13):2156-2167. (PMID: 33879273)
J Affect Disord. 2020 Nov 1;276:883-889. (PMID: 32739706)
Dialogues Clin Neurosci. 2008;10(2):141-52. (PMID: 18689285)
Lancet. 2015 Aug 1;386(9992):461-8. (PMID: 26003379)
Vertex. 2011 Jun;22 Suppl:3-20. (PMID: 21898968)
Int J Neuropsychopharmacol. 2013 Apr;16(3):513-23. (PMID: 22717099)
World Psychiatry. 2018 Oct;17(3):341-356. (PMID: 30192094)
Soc Psychiatry Psychiatr Epidemiol. 2013 Oct;48(10):1601-10. (PMID: 23754681)
BMJ Open. 2017 Sep 27;7(9):e016408. (PMID: 28963287)
JAMA Netw Open. 2023 Aug 1;6(8):e2326910. (PMID: 37531105)
Sci Rep. 2016 May 16;6:25920. (PMID: 27181262)
Br J Clin Pharmacol. 2019 Jul;85(7):1598-1606. (PMID: 30927284)
Cochrane Database Syst Rev. 2017 Jun 28;6:CD009005. (PMID: 28658515)
J Affect Disord. 2017 Aug 1;217:266-280. (PMID: 28437764)
Psychol Med. 2015;45(12):2461-80. (PMID: 25858580)
Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct;398(10):13707-13729. (PMID: 40220024)
Bipolar Disord. 2023 Feb;25(1):7-8. (PMID: 36808784)
Gen Psychiatr. 2021 Jul 23;34(4):e100561. (PMID: 34396043)
Br J Psychiatry. 2001 Jun;178(Suppl 41):S148-56. (PMID: 11388955)
J Affect Disord. 2009 Nov;118(1-3):224-8. (PMID: 19249102)
Bipolar Disord. 2016 Mar;18(2):174-82. (PMID: 26890465)
World Psychiatry. 2008 Feb;7(1):58-62. (PMID: 18458771)
Bipolar Disord. 2009 Jun;11 Suppl 2:4-9. (PMID: 19538681)
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug;398(8):10195-10220. (PMID: 39960558)
Contributed Indexing: Keywords: Antipsychotic; Bipolar disorder; Europe; Lithium; Pharmaceutical utilisation; Prediction
Substance Nomenclature: 0 (Antipsychotic Agents)
0 (Lithium Compounds)
0 (Antimanic Agents)
Entry Date(s): Date Created: 20250628 Date Completed: 20251205 Latest Revision: 20251207
Update Code: 20251207
PubMed Central ID: PMC12678625
DOI: 10.1007/s00210-025-04389-0
PMID: 40580313
Databáza: MEDLINE
Popis
Abstrakt:Mental disorders represent a significant global burden. Despite increasing use of medications, there is no evidence that this burden is decreasing. Lithium has been one of the first-line treatments in bipolar disorder for many years. However, lithium prescribing has plateaued, while antipsychotic use increased over the past decades. This study assesses the current situation and historical trends in 11 European countries for lithium and antipsychotic medications, predicts future trends and presents key characteristics for assessing the appropriate or inappropriate use of lithium. Consumption data for lithium (ATC N05AN) and antipsychotics (ATC N05A) were collected from publicly available sources in European countries, spanning from 1997 to 2024. An analysis of past trends in DID (defined daily dose per 1000 population per day) prescriptions for lithium and antipsychotics was performed and predictions were made until 2030, using ARIMA(0,1,0) models. For each country, the lithium treatment coverage for the prevalence of bipolar disorder was calculated, along with the ratio of antipsychotic to lithium use. Identified similarities and differences were compared between countries and between northern and southern European regions to generalise prescribing patterns. Based on these results, the prescribing behaviour of lithium in the analysed countries was classified as good, moderate or poor. Data were available for 11 countries, including Croatia, Denmark, Estonia, Finland, Germany, Iceland, Italy, the Netherlands, Norway, Spain and Sweden. In all countries, lithium consumption plateaued or declined, while antipsychotic use increased. Projections suggest a continuation of observed trends. Treatment coverage was very low, with the highest rate in Sweden (32.6%) and the lowest in Estonia and Croatia (5.3%). Comparably good prescribing behaviour was observed in the Netherlands, Sweden, Denmark and Iceland. Moderate prescribing was observed in Germany, Spain, Finland and Norway, while poor compliance with lithium prescribing was reported in Italy, Croatia and Estonia. Lithium prescribing is influenced by adherence to guidelines, concerns about side effects and practicability, monitoring infrastructure, clinician training and prescribing preferences. However, antipsychotics also come with severe adverse effects, require extensive monitoring and cause higher healthcare costs compared to lithium. Lithium is increasingly being replaced by antipsychotics in the treatment of bipolar disorder, despite a constant recommendation in guidelines. Lithium remains significantly underused in all countries analysed. A clear north-south shift in prescribing behaviour is observed, with a suggested west-east shift. Northern countries show higher lithium consumption and a lower antipsychotic-to-lithium ratio, reflecting greater adherence to guidelines and more rational prescribing. In contrast, southern countries show lower lithium and higher antipsychotic use. Overall, there is little progress in improving prescribing practices. Withholding lithium from eligible patients is both medically and economically irresponsible. To reduce the burden of mental disorders, effective and evidence-based treatment strategies need to be prioritised, which is currently failed.<br /> (© 2025. The Author(s).)
ISSN:1432-1912
DOI:10.1007/s00210-025-04389-0