EMA scientific guidelines are non-binding documents that reflect the current state-of-the-art in a given area of drug development and evaluation. They aim to support high-quality, ethically sound research that meets regulatory requirements for marketing authorisation applications. As such, guidelines are periodically revised in response to newly established evidence, with updates developed by expert assessors and informed by public consultation.
This latest revision of the depression guideline aims to address several evolving needs in the field, as identified in a
2016 concept paper. These include the
persistent challenge of treatment-resistance: despite the many available treatment options currently available for major depressive disorder, up to 50% of treated patients do not respond adequately. Psychedelics are increasingly being recognised as a potential treatment avenue, particularly for individuals who have not benefited from conventional therapies.
Accordingly, a key addition in Revision 3 is a dedicated section on psychedelics (Section 4.2.3.4.). While the draft version released in 2023 had already signalled this development, the final guideline expands and formalises European regulatory perspectives on how psychedelic compounds should be investigated in clinical studies. PAREA actively contributed to the public consultation of the draft guideline, submitting expert input on the preliminary regulatory considerations for psychedelics.
The section outlines
critical considerations for psychedelic clinical trial design, including challenges around expectancy and unblinding, the need to characterise dose-response relationships and inter-individual variability, and uncertainties around long-term efficacy and safety. It also addresses the complexities of integrating psychedelic administration with psychological or psychotherapeutic support. Additionally, the guideline
encourages sponsors to seek scientific advice early in their development programmes, supporting a case-by-case approach. Many of these recommendations align with the themes discussed in the
EMA’s recent review of completed trials of psychedelics for depression, which examined existing trial methodologies in light of relevant regulatory insights.
With this revision, EMA not only affirms the growing relevance of psychedelic therapies in psychiatry, but also signals a commitment to ensuring their development and potential approval is held to the highest scientific and regulatory standards.
