A Decision Guide for People Facing Deep Life Distress Who Are Considering Psilocybin Therapy

A critical analysis of the benefits and risks of PAT was conducted based on a literature review. Drawing on the available scientific evidence, a preliminary version of the prototype was developed through an iterative process by a multidisciplinary steering committee comprising researchers, physicians, nurses, and patient partners. Each iteration was carefully reviewed and edited until consensus was reached. Revising the content and selecting appropriate graphics were key steps in the development process. The prototype was refined to meet acceptability and usability criteria based on clarity, balanced information, and the use of the best available evidence [18,25,26,27,28].

Recognizing the impact of health literacy on decision-making [29], the decision aid was designed with a focus on language accessibility. The Flesch-Kincaid readability test (FK) was used to measure reading ease, targeting a score suitable for the broadest possible audience [30]. We combined this test with evaluations from potential users to ensure optimal clarity and comprehension [31]. The occasional use of ChatGPT (GPT-4o) helped simplify certain sections to achieve a reading level equivalent to or below the 8th grade, corresponding to a Flesch-Kincaid score of 8 [18,25,26,27,28]. To ensure clarity, medical accuracy, and neutrality, a final literacy validation was conducted by the multidisciplinary steering committee, which included researchers, physicians, nurses, and patient partners.

This qualitative aspect of the study is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (see). Supplementary File S2

Using data from the reading grid, transcriptions, and participants' comments, the first author (A.B.) conducted a thematic synthesis of the feedback based on the topics discussed during the interviews. Transcripts were coded by a single coder (A.B.) with ongoing discussion regarding emerging themes (M.D.). The results of this synthesis were then reviewed with steering committee members to reach a consensus on the changes to be made to the prototype to develop the final version. Qualitative data were analyzed using NVivo 15 software, allowing for systematic coding of the interview transcripts and structuring emerging themes.

This study was approved by the Research Ethics Committee of CHU de Québec–Université Laval (2024-7116). Written informed consent was obtained from all participants. Data were collected anonymously and used solely for research purposes. Results were aggregated, ensuring no participant could be identified. All participants received monetary compensation for their time (50 CAD).

A booklet was developed titled "Envisager la thérapie assistée par psilocybine pour soulager la détresse existentielle/Psilocybin-assisted therapy for existential distress: Making the right choice for you" with the steering committee. The decision aid featured four key sections to support informed decision-making regarding PAT. One section provided educational information on existential distress and PAT, outlining potential benefits, risks, contraindications, and possible drug interactions. Another offered an objective comparison of therapeutic options, such as medications, psychotherapy, spiritual interventions, and PAT, helping patients understand how each approach fits within the broader spectrum of available treatments for existential distress. The prototype also encouraged personal reflection on values and care priorities to support decisions that align with individual goals [19]. The document included visual elements, a values clarification scale, and a frequently asked questions (FAQ) section to enhance understanding and user engagement. These four sections were selected based on IPDAS standards, prior research on shared decision making, and feedback from patients and healthcare professionals, highlighting the need for balanced information, comparison of options, values clarification, and accessible formats.

The evaluation focused on the booklet's overall quality and four key sections of the decision aid, each rated on a satisfaction scale ranging from 1 (not at all satisfactory) to 4 (very satisfactory). The overall quality of the decision aid was considered satisfactory, with an average score of 3.2 from patients and 3.6 from healthcare professionals, indicating a generally positive perception (see Figure 2).

Section 1 of the decision aid aimed to expand knowledge about PAT within the context of existential distress and received an average rating of 3.4 from both groups. Section 2 compared PAT with other available treatment options and was rated 3.2 by all. Section 3, which encouraged reflection on personal values and care priorities, received a higher mean score from professionals (3.6) than from patients (2.6). This discrepancy may reflect differences in familiarity and comfort with structured values clarification tools. Patients may have perceived the section as less intuitive or more demanding, while professionals, accustomed to such frameworks, rated it more positively. These results suggested that clearer guidance and concrete examples were needed to optimize patient engagement with this section (see Figure 2).

Overall, these results point to high satisfaction, especially among healthcare professionals, with some areas for improvement. Section 3 was noted explicitly as needing revision due to differences in perception between the two groups. Based on participant feedback, this section was revised to better address user needs and improve the clarity and usefulness of the values clarification process.

Thematic analysis of the semi-structured interviews revealed several key themes that informed revisions to the decision aid tool (see Table 2, Table 3 and Table 4). These included the balance of options presented, the content, the clarity of the information, the length and structure of the document, and the most appreciated features.

Regarding the balance of options, participants noted a perceived bias in favor of PAT, which they felt could influence patients' decision making. As illustrated by healthcare professionals' quotes (Table 3), some stressed the importance of including information on other therapeutic approaches, such as existential psychotherapy, ketamine-assisted therapy, and spiritual interventions. Several patients also noted the disproportionate focus on PAT (Table 2), although many acknowledged the limited availability of effective alternatives. The content was thus revised to better balance the presentation of available treatment options (Table 4).

The content of the decision aid itself also elicited varied reactions. Healthcare professionals highlighted the importance of clearly presenting PAT as an experimental option, mainly intended for refractory cases. Some also mentioned the risk of temporary symptom exacerbation following psilocybin administration (Table 3). Patients appreciated the description of existential distress but expressed concerns about specific terminology, particularly the phrase "large dose," which was perceived as anxiety-provoking (Table 2). To address these concerns, a preamble clarifying the experimental nature of PAT was added, sensitive terms were reformulated, and the risks and benefits associated with the therapy were better contextualized (Table 4).

The clarity of the information and health literacy were also central concerns. Although the decision aid tool was generally well received, several participants brought up difficulties in understanding certain concepts or visual elements. Healthcare professionals recommended simplifying certain complex medical terms, while patients pointed out confusion regarding the values clarification scale and comparative tables (Table 2 and Table 3). In response, the language was simplified, visuals were revised, and the comparative table was redesigned to improve readability and relevance (Table 4).

Opinions were mixed regarding the length of the decision aid and the order of the sections. While some participants considered the content comprehensive and relevant, others reported cognitive fatigue when reading the material and suggested that the document could better balance information richness and accessibility. Participants also proposed reordering some sections to facilitate navigation (Table 2 and Table 3). As a result, the sequence of sections was revised, with the FAQ section moved before the values clarification scale, and some less relevant elements were removed (Table 4).

Several aspects of the decision aid tool were unanimously appreciated. Both patients and healthcare professionals highlighted the relevance of the holistic approach, which addresses psychological, existential, and spiritual dimensions. They also appreciated the sections allowing personal questions to be noted and the detailed information on contraindications and drug interactions (Table 2 and Table 3). Overall, the decision aid was perceived as a useful and valuable resource to support patients in a thoughtful and informed decision-making process, provided it is adapted to the users' practical needs and clinical contexts.

Following the qualitative evaluation, a final version of the decision aid was produced and validated by the steering committee. This version included key modifications intended to improve readability, balance the presentation of treatment options, elucidate the values clarification scale, and enhance the overall accessibility and utility of the information. The structure of the booklet, organized into four main sections, was optimized to facilitate navigation and support personal reflection. Although we re-presented the final version to participants, only 2 patients and 1 healthcare professional completed the evaluation grid. Due to the patients' fragile health, we did not recontact them further. Given the small sample size, we do not report post-evaluation statistics. However, qualitative feedback indicates that the final version was improved and generally perceived as clear, balanced, and useful. One patient mentioned: "I appreciate its ease of use and understanding, and the fact that it can be available at home to return to when needed. The booklet is, in my opinion, a good introduction and a helpful support. I don't really have (any suggestions for improvement) at this stage." A doctor said: "Very well explained; clear vocabulary that does not require prior knowledge, risks and benefits clearly presented, use of decision-making support, tables and figures that strongly support the content".

Following the initial development of the decision aid in French, a North American English version was produced and revised by a patient-partner and a healthcare professional, both native English speakers involved in PAT, to ensure clarity, accuracy, and relevance for English-speaking users. For additional rigor, we also assessed readability using the Flesch-Kincaid scale to maintain consistency with the French version, which was required to achieve a score between 7 and 8; the English version reached 7.6, exactly within the recommended target for decision aids. Both versions are available in. Supplementary Files S5 and S6

The final decision aid meets the quality criteria established by IPDAS and was deemed relevant, balanced, and useful by participants in supporting decision making for individuals facing existential distress [19,22,26,27,39].

The proposed decision aid tool aligns with the broader tradition of decision-support interventions developed for complex medical contexts, where multiple therapeutic options are available and uncertainty regarding benefits and risks remains high [18,43]. For example, decision aids used in the treatment of cancer or cardiovascular diseases have demonstrated significant benefits in terms of patient satisfaction and adherence to chosen treatments [22,39,41,44,45]. However, very few tools have been specifically designed to support decision making in palliative care, highlighting the innovative nature of this initiative within the field of existential distress management [9,46].

The development process had several strengths, including using established frameworks for decision aid design, guidance from a multidisciplinary steering group, incorporation of direct participant feedback, and data collection through semi-structured interviews. The involvement of patient partners throughout the development process reinforces the decision aid's clinical relevance and validity. However, several limitations must also be acknowledged. The recruitment for this study was challenging, potentially due to the demands of the interview process on participants. Individuals living with serious illnesses often face time and energy constraints, making participation more difficult. In addition, the therapeutic use of psilocybin remains highly innovative, limiting the number of patients and healthcare professionals interested in and qualified to participate. Lastly, there is a scarcity of professionals with experience evaluating decision aids related to such emerging therapies, further reducing the recruitment pool. As a result, the sample size is relatively small (n = 10), relatively homogeneous (predominantly highly literate participants from the same geographic area), which limits the generalizability of the findings and warrants caution against broad application at this stage. Nevertheless, data saturation appeared to have been reached during the semi-structured interviews, suggesting that the main relevant themes were adequately explored [47]. A larger-scale study could help confirm these findings and further deepen the understanding of decision-making needs in the context of existential distress [48]. A further limitation concerns the use of a single coder for the qualitative analysis. This approach was supported by using field notes and a reflexive journal to enhance transparency. To help mitigate this limitation, the first author (A.B.) documented the data analysis process and regularly met with the last author (M.D.) to discuss and resolve disagreements, ensuring consensus at each stage [49]. Furthermore, the process was iteratively reviewed by the multidisciplinary steering committee. This group provided oversight, validated emerging themes, and ensured that the analysis remained balanced, rigorous, and reflective of diverse perspectives, thereby helping to reduce the risk of bias inherent in single-coder analysis.

A related consideration is that only a small number of participants re-evaluated the final version of the decision aid, which limited the possibility of a full second round of validation. Nevertheless, the feedback obtained indicated improvements in clarity, balance, and usefulness, and the final version was subsequently reviewed and endorsed by team members with lived experience of PAT.

It is also worth noting that while healthcare professional participants had substantial experience in palliative care, they were all located in the same geographical region, limiting the diversity of perspectives. Most patients living with serious illness participants were also highly educated and health literate, which may have biased the evaluation of the decision aid's accessibility. To address this, future studies should include participants with broader literacy levels to better assess the decision aid's usability across diverse populations. Also, most patient participants in this study were women, which may have influenced their informational needs and approaches to values clarification. Achieving greater gender balance in future research could help explore whether men have different perspectives or decision-making preferences in this context.

Lastly, although the decision aid was originally developed in French and translated into English, linguistic and cultural nuances may still affect its interpretation and applicability in other settings. To address this, systematic cultural adaptation of translations, cognitive debriefing with patients and healthcare professionals from diverse backgrounds, and pilot testing in multiple contexts will be required to ensure clarity, accessibility, and relevance across settings.

This study underscores the potential role of a decision aid in assisting patients in navigating complex end-of-life choices. The decision aid offers more than just informational content, as is typical of an education booklet. By clarifying the risks and benefits associated with PAT, the decision aid promotes informed decision-making aligned with patients' values while enhancing dialogue with healthcare professionals. It was designed to support patients in engaging in informed conversations with healthcare professionals, helping them assess the relevance of PAT or consider other options, and present the available options for addressing existential distress in a clear and accessible manner [19].

The findings of this study open several avenues for future research. It would be valuable to assess the decision aid's actual impact on the quality of decision-making and patient experiences over the longer term, particularly by comparing decision trajectories with and without the decision aid. In this regard, conducting a randomized controlled trial would be an essential next step to rigorously evaluate the decision aid's effectiveness in supporting patient decision-making. Given the growing interest in PAT and the time-intensive nature of conducting a randomized trial, we felt it was important to promptly make the decision aid tool available for clinical use. Feedback is currently being gathered from real-world settings to inform the development of an improved future edition. These efforts are being carried out in collaboration with interdisciplinary teams across multiple institutions and will contribute to future initiatives aimed at scaling up implementation and promoting broader dissemination across diverse care environments.

Developing digital formats, such as mobile applications or interactive platforms, could further improve the decision aid's accessibility, especially for patients with varying literacy levels. These technologies would also facilitate their integration into clinical workflows by offering real-time access to patient preferences.

Finally, the methodological approach developed here could be extended to other emerging therapies, such as ketamine-assisted therapy or psychospiritual interventions, by designing similar decision support tools tailored to complex medical decision-making contexts. The decision aid will be made available as a downloadable PDF or printed format from the research team's website: www.p3a.ca↗.