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Professional Responsibility and Off-Label Prescribing in Psychiatry: An International Framework for Evidence, Consent, and Documented Risk Management

  • Claudia Libri 1,*,   
  • Mario Pinzi  1,   
  • Stavroula I. Bargiota 2,   
  • Pietro Carmellini 1,   
  • Francesco Fargnoli 1,   
  • Giacomo Gualtieri 3

Received: 27 Jul 2026 | Revised: 16 Aug 2026 | Accepted: 01 Sep 2026 | Published: 04 Sep 2026

Abstract

Off-label prescribing is a structural feature of psychiatric practice because regulatory labels do not always keep pace with evidence, symptom-based treatment needs, multimorbidity, or populations under-represented in registration trials. This narrative comparative review examines how professional responsibility is shaped by regulatory and professional frameworks in Italy, the European Union and Greece, the United States, the United Kingdom, China, Japan, India, and Australia–New Zealand. Across otherwise different systems, five recurring safeguards emerge: an individualized clinical need; explicit consideration of licensed alternatives; a supportable evidentiary rationale; meaningful informed consent; and prospective documentation, monitoring, and reassessment. The authors conceived and drafted the manuscript; OpenAI Codex assisted with language editing, literature/regulatory checks, and formatting; all AI output was reviewed and verified by the authors, who take full responsibility for the content. Greece illustrates how national reimbursement and exceptional-review mechanisms operate within the European setting, while recent Greek pediatric data also show the practical relevance of label gaps. China has moved from a legal grey area to explicit statutory conditions for off-label use, whereas Japan provides a regulatory route for converting well-established clinical knowledge into approved indications. Selected European and US labels for aripiprazole, lurasidone, cariprazine, and brexpiprazole demonstrate that the same evidence can produce different authorized indications across jurisdictions. Off-label status is therefore neither a proxy for poor care nor a guarantee of therapeutic innovation. Professional defensibility depends on the quality, transparency, proportionality, and reversibility of the decision process. A cross-jurisdictional checklist is proposed to support safer psychiatric prescribing without collapsing clinical judgment into mere label compliance.

References 

  • 1.

    Wittich, C.M.; Burkle, C.M.; Lanier, W.L. Ten Common Questions (and Their Answers) about Off-Label Drug Use. Mayo Clin. Proc. 2012, 87, 982–990. https://doi.org/10.1016/j.mayocp.2012.04.017.

  • 2.

    O’Brien, P.L.; Cummings, N.; Mark, T.L. Off-Label Prescribing of Psychotropic Medication, 2005–2013: An Examination of Potential Influences. Psychiatr. Serv. 2017, 68, 549–558. https://doi.org/10.1176/appi.ps.201500482.

  • 3.

    dos Santos, H.M.M.; Botelho-Souza, L.F.; Nunes, R.; et al. Thematic Mapping of Off-Label Prescription in Psychiatry and Its Implications for Bioethics, Human Rights, and Clinical Practice: A Scoping Review. Front. Psychiatry 2026, 17, 1705340. https://doi.org/10.3389/fpsyt.2026.1705340.

  • 4.

    European Commission. Study on Off-Label Use of Medicinal Products in the European Union. Available online: https://health.ec.europa.eu/document/download/8fbaaf48-32ce-4191-98c6-cfb76e783d47_en (accessed on 23 July 2026).

  • 5.

    Pesiou, S.; Barcelo, R.; Papazisis, G.; et al. Prevalence of Use of On-Label and Off-Label Psychotropics in the Greek Pediatric Population. Front. Pharmacol. 2024, 15, 1348887. https://doi.org/10.3389/fphar.2024.1348887.

  • 6.

    Kharadi, D.; Patel, K.; Rana, D.; et al. Off-Label Drug Use in Psychiatry Outpatient Department: A Prospective Study at a Tertiary Care Teaching Hospital. J. Basic Clin. Pharm. 2015, 6, 45–49. https://doi.org/10.4103/0976-0105.152090.

  • 7.

    Gadaria, S.; More, S.A.; Pal, V.S.; et al. A Prospective Observational Study on the Off-Label Use of Medications in the Psychiatry Outpatient Department of a Tertiary Care Hospital. Indian J. Pharmacol. 2026, 58, 96–100. https://doi.org/10.4103/ijp.ijp_184_25.

  • 8.

    Verdoux, H. Antipsychotic Off-Label Use in the 21st Century: An Enduring Public Health Concern. Dialogues Clin. Neurosci. 2025, 27, 1–12. https://doi.org/10.1080/19585969.2025.2449833.

  • 9.

    Tanana, L.; Harrison, C.; Nishtala, P.S.; et al. Factors Associated with the Off-Label Use of Psychotropic Medicines in Children and Adolescents: A Scoping Review. Aust. N. Z. J. Psychiatry 2026, Epub ahead of print. https://doi.org/10.1177/00048674261475163.

  • 10.

    Italian Republic. Law 8 April 1998, No. 94: Conversion, with Amendments, of Decree-Law 17 February 1998, No. 23; Official Gazette, General Series No. 86, 14 April 1998. Available online: https://www.gazzettaufficiale.it/eli/id/1998/04/14/098G0128/sg (accessed on 23 July 2026).

  • 11.

    Italian Republic. Law 24 December 2007, No. 244, Article 2, Paragraphs 348–349; Official Gazette, General Series No. 300, 28 December 2007, Ordinary Supplement No. 285. Available online: https://www.normattiva.it/uri-res/N2Ls?urn:nir:stato:legge:2007-12-24;244 (accessed on 31 August 2026).

  • 12.

    Italian Medicines Agency. Early Access and Off-Label Use. Available online: https://www.aifa.gov.it/en/accesso-precoce-uso-off-label (accessed on 23 July 2026).

  • 13.

    Italian Republic. Law 8 March 2017, No. 24, Article 5: Clinical-Care Good Practices and Guideline Recommendations. Available online: https://www.normattiva.it/uri-res/N2Ls?urn:nir:stato:legge:2017-03-08;24~art5= (accessed on 23 July 2026).

  • 14.

    Italian Republic. Law 22 December 2017, No. 219, Article 1: Informed Consent. Available online: https://www.normattiva.it/uri-res/N2Ls?urn:nir:stato:legge:2017-12-22;219!vig= (accessed on 23 July 2026).

  • 15.

    Hellenic Republic, Ministry of Health. Ministerial Decision ΔΥΓ3(α)/οικ.Γ.Υ.154 of 29 February 2012: Medicinal Products Outside Approved Indications; Government Gazette (ΦΕΚ) B′ 545/1 March 2012. Official text available from the National Printing House. Available online: https://search.et.gr/el/fek/?fekId=476939 (accessed on 31 August 2026).

  • 16.

    Hellenic Republic. Law 4316/2014, Article 47: Coverage of Medicines Outside Approved Indications, amending Article 12(1)(a) of Law 3816/2010; Government Gazette (ΦΕΚ) A′ 270/24 December 2014. Official text available from the National Printing House. Available online: https://www.taxheaven.gr/law/4316/2014 (accessed on 31 August 2026).

  • 17.

    U.S. Food and Drug Administration. Understanding Unapproved Use of Approved Drugs: Off-Label. Available online: https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label (accessed on 23 July 2026).

  • 18.

    U.S. Food and Drug Administration. Communications from Firms to Health Care Providers regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers. Guidance for Industry. Available online: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/communications-firms-health-care-providers-regarding-scientific-information-unapproved-uses (accessed on 23 July 2026).

  • 19.

    General Medical Council. Prescribing Unlicensed Medicines. Available online: https://www.gmc-uk.org/professional-standards/the-professional-standards/good-practice-in-prescribing-and-managing-medicines-and-devices/prescribing-unlicensed-medicines (accessed on 23 July 2026).

  • 20.

    People’s Republic of China. Physician Law of the People’s Republic of China, Article 29; adopted by the Standing Committee of the National People’s Congress on 20 August 2021, in force 1 March 2022 (Presidential Order No. 94) (in Chinese). Available online: http://www.npc.gov.cn/npc/c2/c30834/202108/t20210820_313104.html (accessed on 31 August 2026).

  • 21.

    Zuo, W.; Sun, Y.; Liu, R.; et al. Management Guideline for the Off-Label Use of Medicine in China (2021). Expert Rev. Clin. Pharmacol. 2022, 15, 1253–1268. https://doi.org/10.1080/17512433.2022.2120468.

  • 22.

    Liang, S.; Cai, F. Off-Label Drug Use in China after the Physician Law (2021): Legal Challenges and Solutions. Front. Pharmacol. 2025, 16, 1547418. https://doi.org/10.3389/fphar.2025.1547418.

  • 23.

    Si, W.; Ma, P. Judicial and Legislative Practice and Related Suggestions on Off-Label Drug Use in China. BMC Health Serv. Res. 2023, 23, 312. https://doi.org/10.1186/s12913-023-09293-y.

  • 24.

    Pharmaceuticals and Medical Devices Agency. Public Knowledge-Based Applications for Prescription Drugs. Available online: https://www.pmda.go.jp/review-services/drug-reviews/review-information/p-drugs/0016.html (accessed on 23 July 2026).

  • 25.

    Maeda, H.; Fukuda, Y.; Uchida, M. Assessment of Drugs Approved by Public Knowledge-Based Applications (Kouchi-Shinsei) during the Last Two Decades in Japan. Clin. Pharmacol. Ther. 2021, 110, 1127–1135. https://doi.org/10.1002/cpt.2332.

  • 26.

    Hinomura, A.; Obata, D.; Matsubayashi, J.; et al. Facts and Issues of Submitting Applications (Public Knowledge-Based Applications) for Unapproved and Off-Label Drugs with High Medical Needs in Japan. Curr. Ther. Res. 2026, 104, 100819. https://doi.org/10.1016/j.curtheres.2025.100819.

  • 27.

    Aino, S.; Nanbu, S.; Narukawa, M. Pediatric Off-Label Use in Japan: Insights from the National Database of Health Insurance Claims. Pediatr. Int. 2026, 68, e70319. https://doi.org/10.1111/ped.70319.

  • 28.

    Therapeutic Goods Administration. Supply an Unapproved Therapeutic Good (Sponsors). Available online: https://www.tga.gov.au/products/unapproved-therapeutic-goods/access-pathways/supply-unapproved-therapeutic-good-sponsors (accessed on 23 July 2026).

  • 29.

    Lehman, K.; Aroney, E. A Guided Framework for Assessing Off-Label Medication Use in Psychiatry. Australas. Psychiatry 2024, 32, 63–67. https://doi.org/10.1177/10398562231211168.

  • 30.

    Royal Australian and New Zealand College of Psychiatrists. Professional Practice Guideline 4: ‘Off-Label’ Prescribing in Psychiatry, Version 4.0. Available online: https://www.ranzcp.org/getmedia/edc66b1d-005b-411d-b277-5c7fddc71ba2/ppg-4-off-label-prescribing-december-2023.pdf (accessed on 31 August 2026).

  • 31.

    Gazarian, M.; Kelly, M.; McPhee, J.R.; et al. Off-Label Use of Medicines: Consensus Recommendations for Evaluating Appropriateness. Med. J. Aust. 2006, 185, 544–548. https://doi.org/10.5694/j.1326-5377.2006.tb00689.x.

  • 32.

    European Medicines Agency. Abilify: EPAR—Product Information. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/abilify (accessed on 23 July 2026).

  • 33.

    U.S. Food and Drug Administration. Abilify (Aripiprazole) Prescribing Information. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021436s046s050lbl.pdf (accessed on 23 July 2026).

  • 34.

    European Medicines Agency. Latuda: EPAR—Product Information. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/latuda (accessed on 23 July 2026).

  • 35.

    U.S. Food and Drug Administration. Latuda (Lurasidone Hydrochloride) Prescribing Information. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/200603s041lbl.pdf (accessed on 23 July 2026).

  • 36.

    European Medicines Agency. Reagila: EPAR—Product Information. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/reagila (accessed on 23 July 2026).

  • 37.

    U.S. Food and Drug Administration. Vraylar (Cariprazine) Prescribing Information. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204370s014s015s016s017lbl.pdf (accessed on 23 July 2026).

  • 38.

    European Medicines Agency. Rxulti: EPAR—Product Information. Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/rxulti (accessed on 23 July 2026).

  • 39.

    U.S. Food and Drug Administration. Rexulti (Brexpiprazole) Prescribing Information. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/205422s014lbl.pdf (accessed on 23 July 2026).

  • 40.

    Radley, D.C.; Finkelstein, S.N.; Stafford, R.S. Off-Label Prescribing among Office-Based Physicians. Arch. Intern. Med. 2006, 166, 1021–1026. https://doi.org/10.1001/archinte.166.9.1021.

  • 41.

    Holopainen, A.K.; Vainiotalo, P.A.; Arrhenius, B.P.; et al. Systematic Review: Efficacy of Off-Label Antipsychotic Use in Children and Adolescents with Obsessive-Compulsive, Mood Dysregulation, Depression, Anxiety, and Sleep-Related Disorders. Eur. Child Adolesc. Psychiatry 2026, Epub ahead of print. https://doi.org/10.1007/s00787-026-03049-9.

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Libri, C.; Pinzi , M.; Bargiota, S. I.; Carmellini, P.; Fargnoli, F.; Gualtieri, G. Professional Responsibility and Off-Label Prescribing in Psychiatry: An International Framework for Evidence, Consent, and Documented Risk Management. East West Journal of Psychiatry and Mental Health 2026, 1 (1), 4.
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