Thematic Mapping of Off-Label Prescription in Psychiatry and Its Implications for Bioethics, Human Rights, and Clinical Practice: A Scoping Review

Humberto Müller Martins dos Santos^1*Luan Felipo Botelho-Souza²Rui Nunes¹Ivone Duarte¹

• ¹Universidade do Porto Faculdade de Medicina, Porto, Portugal
• ²Faculdades Integradas Aparício Carvalho, Porto Velho, Brazil

Mental disorders represent a major global public health challenge, and off-label prescribing in psychiatry has emerged as a common practice given the scarcity of approved therapeutic options. Although often necessary, this practice involves ethical and legal dilemmas that require analysis through the lens of bioethics and human rights. The objective of this scoping review was to map the scientific literature on off-label prescription in psychiatry, identifying its impacts on bioethics, human rights, and clinical practice. The study followed PRISMA-ScR guidelines, with searches conducted between July 2024 and Dezember 2025 in PubMed, the Virtual Health Library (BVS), PsycINFO (APA), Web of Science, and the ClinicalTrials.gov register. A total of 1,828 records were identified, of which 38 met the inclusion criteria (last 15 years, with exceptions for foundational historical studies, focusing on psychiatry and bioethical principles). The protocol was prospectively registered in INPLASY (INPLASY202590058). Thematic analysis involved constructing an evidence matrix and keyword co-occurrence networks, using VOSviewer to explore conceptual clusters. The results highlighted the centrality of the terms off-label, ethics, informed consent, and human rights, demonstrating that the main concerns revolve around clinical responsibility, patient autonomy, and the protection of health as a fundamental right. Special populations, children, adolescents, and pregnant women, stood out as highly vulnerable groups, frequently exposed to prescriptions in contexts of limited evidence. The co-occurrence graph further revealed peripheral subthemes, such as health litigation and pharmaceutical regulation, interconnected with the central core. Thus, the literature reflects a multidimensional concern, predominantly emphasizing ethical and legal dimensions, while pointing to critical gaps in robust clinical evidence and regulatory integration. These findings reinforce the need for clear guidelines, inclusive clinical research, and public policies that ensure safe, equitable practices aligned with bioethical principles and human rights.