Facilitators and barriers to participation of patients with treatment resistant depression in a randomised controlled trial of two forms of personalised magnetic resonance imaging targeted transcranial magnetic stimulation (the BRIGhTMIND trial)

Facilitators and barriers to participation of patients with treatment resistant depression in a randomised controlled trial of two forms of personalised magnetic resonance imaging targeted transcranial magnetic stimulation (the BRIGhTMIND trial) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Facilitators and barriers to participation of patients with treatment resistant depression in a randomised controlled trial of two forms of personalised magnetic resonance imaging targeted transcranial magnetic stimulation (the BRIGhTMIND trial) Clement Boutry, Lucy Webster, Louise Thomson, Delilah Harding, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5319588/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jul, 2025 Read the published version in BMC Psychiatry → Version 1 posted 4 You are reading this latest preprint version Abstract Background. Magnetic resonance imaging (MRI) can personalise the site of transcranial magnetic stimulation (TMS) delivered as a course of 20 sessions for treatment-resistant depression (TRD). Facilitators and barriers to a randomised controlled trial (RCT) of MRI personalised TMS is understudied. Aim. To explore facilitators and barriers behind RCT participants’ experience of personalised MRI-targeted TMS in people with TRD. Methods. Nineteen participants from the BRIGhTMIND RCT of two forms of MRI personalised TMS, completed semi-structured interviews exploring the reasons behind the uptake and experience of TMS. The sample included fifteen participants who completed the treatment course and four who declined to proceed before randomisation. Interviews were analysed using thematic analysis, co-produced between researchers and patients and public involvement contributors. Results . Facilitators were “hope” regarding the treatment itself, the influence of research staff, interest in a new treatment, and altruism. Barriers were concerns about their ability to commit to the trial and the nature of the TMS itself. MRI was neither a facilitator nor a barrier to TMS. Throughout the themes, clinicians and researchers made a difference by explaining and setting realistic expectations of the treatment and building rapport through daily patient contact. The ability to offer TMS outside office hours would be a great advantage for patients in employment. Conclusion. The study highlights the importance of understanding patients’ concepts and experiences of TMS. The provision of optimal information to patients and the most efficacious, acceptable regimes of TMS delivery may maximise participation (Trial registration number ISRCTN19674644). Transcranial magnetic stimulation treatment-resistant depression magnetic resonance imaging study recruitment 1. Introduction Transcranial magnetic stimulation (TMS) is a National Institute for Health and Care Excellence (NICE) approved intervention using the application of magnetic pulse to change brain activity for both depression and treatment-resistant depression (TRD) (NICE, 2015). However, it is still only available as a clinical intervention in a minority of mental health services in the UK and internationally. Repetitive TMS (rTMS) is the traditional form delivered at a standard site in 37.5-minute sessions on 20 or more occasions. Benefits typically only last 1-3 months with a high degree of variability between individuals (NICE, 2015; Health Quality Ontario, 2016). Intermittent theta burst stimulation (iTBS) is an alternative patterned form of TMS that mimics the brain’s natural electromagnetic rhythm producing long-term and therefore might be effective for a longer duration of time (Larson and Munkácsy, 2015). It is equally effective for treatment-resistant depression (Blumberger et al. , 2018; Bulteau et al. , 2022; Morriss et al. , 2024) and requires a shorter duration of administration (Blumberger et al. , 2018), thereby increasing patient throughput in a clinical TMS service. Whilst evidence suggests that TMS in depression is generally well-tolerated (Fitzgerald, George and Pridmore, 2022), only a small number of studies have investigated the facilitators and barriers to accessing TMS treatments for depression or other conditions. Clinicians have been identified as having an important role in facilitating engagement in TMS. This role goes beyond just delivering TMS treatment to include engaging in constructive therapeutic conversations, providing a relaxing and friendly environment, and supportive long-term management (Mallon et al. , 2020; Stillianesis et al. , 2022). Patients’ initial impression of TMS and the equipment used to deliver it is thought to be a decisive factor, influencing both their perceptions of treatment effectiveness and also causing fear and apprehension in some (Stillianesis et al. , 2022). Whilst prior research provides some implications for practice guidance in engaging patients with rTMS, the facilitators and barriers to recruitment to a research trial offering rTMS or iTBS have not been explored. We conducted qualitative interviews that ran parallel to the BRIGhTMIND study, a multi-site RCT in which patients with TRD received 20 sessions of either rTMS or connectivity-guided intermittent theta burst stimulation (cgiTBS), a form of iTBS (Morriss et al. , 2020, 2024; Pszczolkowski et al. , 2022), to explore the barriers and facilitators to the recruitment of participants in the trial. 2. Methods The study employed a qualitative analysis of semi-structured interviews conducted with participants in the BRIGhTMIND trial. Ethical approval was provided by NHS Research Ethics Committee (ref: 18/EM/0232). In the BRIGhTMIND trial, 255 participants with TRD were recruited. They were informed that we were testing two different forms of TMS treatment that were personalised using MRI scans and neuronavigation - allowing for precise targeting of the coil placement area (rTMS versus cgiTBS), to extend the duration of improvement in depression symptoms from 1-3 months to 6 months. They were to be randomised to one of these two treatments and they would need to attend a baseline assessment and MRI scan, complete 20 sessions of TMS over 4-6 weeks, have further clinical assessments at 8-, 16- and 26 weeks post randomisation, with a further MRI scan at 16 weeks. They were provided further information on potential adverse effects and details on the procedures involved in the trial. We provided materials showing how we approached clinicians and participants, including changes as a result of the COVID-19 pandemic, and our recruitment strategy (see supplementary material 1-4). 2.1 Data Collection Three sets of participants were anticipated to be recruited to this study using purposive sampling: i) participants who completed TMS treatments were invited to participate after their 26-week follow-up assessment; ii) participants who withdrew from the main BRIGhTMIND trial during or after commencing TMS treatments – thus, did not complete the treatment course (i.e. withdrawn participants); and iii) participants who had returned a reply slip to the research team expressing interest in the main BRIGhTMIND trial, but declined to participate before being randomised (i.e. declined participants). Recruitment took place across four of the five UK NHS sites participating in the main trial. Eligible participants were sent an invitation letter, an information sheet highlighting the aims and content of the study, a copy of the consent form, and a reply slip for the interview study. Those that returned reply slips expressing interest were contacted to schedule an interview, conducted by researchers working on the main BRIGhTMIND clinical trial with experience in conducting qualitative interviews. Before the interview, the researcher reviewed the information sheet with the participants, who were then given the opportunity to ask questions, before giving consent to participate. Written consent was obtained for face-to-face interviews, and verbal consent was obtained and formally recorded for telephone interviews. Interviews were recorded on an encrypted digital voice recorder and transcribed using a professional transcription service. The interviews were conducted between October 2019 and March 2022 and lasted between eight and 26 minutes. Five were completed in person, whilst the remaining interviews were conducted remotely due to either participant preference or COVID-19 pandemic-related restrictions. Semi-structured topic guides reviewed by a group of people with lived experience of TRD were used to explore participants’ experiences of the facilitators and barriers to taking part in the BRIGhTMIND RCT which involved either receiving rTMS or cgiTBS (Morriss et al. , 2020). Topic guides included four broad questions: (1) how they found out about the trial; (2) their initial reaction on hearing about the trial and treatment involved; (3) the factors that motivated their decision about participation; (4) whether they had any concern about taking part in the trial. Participants who received TMS treatments as part of the main BRIGhTMIND trial were also asked about their experience of the trial and the acceptability of the treatment, which will be reported in a separate paper. Topic guides can be found in the supplemental material 5 and 6. 2.2 Participants Out of the 255 BRIGhTMIND trial participants, Nineteen were interviewed: seven from the Nottingham site, seven from the London site, three from the Northampton site, and two from the Newcastle site; aged 29-67 years ( M = 49.7, SD = 12.6 years). We did not recruit any participants from the Oldham site who joined the study after March 2022. The participants included ten males and nine females, with 17 (89.5%) white (British or other), and the remaining two participants of Asian or Asian British ethnicity. Eight (42.1%) participants were in full-time or other employment, seven (36.8%) were unemployed and four (21.1%) were retired. Fifteen (78.9%) of the interviewed participants had completed the full cycle of TMS treatments and follow-up assessments, and four (21.1%) had declined to participate in the trial before randomisation into treatments. None of the participants who withdrew from the trial during or after treatments returned the reply slips expressing an interest in this study. Of those that completed treatments, seven (36.8%) participants received rTMS treatment and eight (42.1%) received cgiTBS treatment. See Table 1 for more information. Table 1: Participants’ demographics Service User ID Code Site Participation in trial Treatment arm 1 Nottingham Full rTMS 2 Nottingham Full rTMS 3 Nottingham Full Cgi TBS 4 London Full rTMS 5 London Full Cgi TBS 6 Nottingham Full rTMS 7 Northampton Full rTMS 8 Northampton Full Cgi TBS 9 London Full Cgi TBS 10 Newcastle Full Cgi TBS 11 Nottingham Full Cgi TBS 12 Newcastle Declined n/a 13 London Declined n/a 14 London Declined n/a 15 Northampton Declined n/a 16 Nottingham Full Cgi TBS 17 London Full rTMS 18 Nottingham Full cgiTBS 19 London Full rTMS 2.3 Data Analysis An inductive thematic framework analysis approach was used (Ritchie and Spencer, 2002; Gale et al. , 2013). Initially, transcripts were repeatedly read by two researchers (CB and LW) before coding, to allow researchers to familiarise and become immersed in the data before coding six of them separately (Nowell et al. , 2017), to ensure consistency and reliability of coding (Lincoln and Guba, 1985). One researcher (CB) coded the remaining 13 transcripts. The initial codes identified the interesting and most relevant features of the data, focused on the research objectives. Researchers (CB) and (LW) reached consensus that data had reached saturation as no new or meaningful codes emerged after 12 transcripts (Kerr, Nixon and Wild, 2010), therefore, no additional interviews were required. However, after this, some further interviews were conducted to see if any new data was identified due to the COVID-19 pandemic. Following this, researchers (CB and LW) summarised the initial codes into broader categories. A discussion then took place with the principal investigator and qualitative lead (LT), whereby the overarching framework of themes was identified. The data was then input into the framework matrix using Nvivo 12. The research team scrutinised the final structure and codes which aided the refinement of the framework by renaming, merging/removing themes and sub-themes. The framework of themes and sub-themes were presented to the main trial’s patient and public involvement (PPI) group and then to researchers involved in the BRIGhTMIND study recruitment, for feedback and to support the interpretation of the findings. This allowed us to check the credibility of the analysis and results, further improving the trustworthiness of the results (Lincoln and Guba, 1985). The results were also used to inform the main trial’s ongoing recruitment and other procedures, demonstrating their transferability (Lincoln and Guba, 1985). 3. Results Themes and sub-themes are summarised in Table 2. Table 2: Themes and sub-themes Facilitators Barriers Hope Commitment concerns Influence of staff Treatment-related concerns Interest in new treatments Altruism 3.1 Facilitators Participants exhibited hope and optimism towards the innovative TMS treatment, driven by the desire for an effective alternative to medications. Positive interactions with compassionate and supportive staff, a desperate need for relief from TRD symptoms, and a sense of altruism towards helping others were key factors that motivated their participation and engagement in the trial. 3.1.1 Hope Supplementary material 7, Table 1 shows the subthemes to the hope theme with supporting quotes. Keen to try alternative treatments Participants’ enthusiasm to get better translated into openness towards the innovative treatment. There was optimism and hope that TMS treatments could help where other treatments had previously failed in relieving their depression. The positivity and hope stemmed from TMS being a different type of treatment option that targeted the cause of depression and “what physically happens to the brain rather than simply testing chemical levels” (Participant 14). Participants believed that this offered a credible alternative to pharmacological treatments. Grateful for opportunity Participants also expressed feeling grateful and privileged that they were offered the opportunity to receive this treatment which affirmed an aspiration to get better. Participants felt glad that their symptoms made them eligible to access the treatment as if their participation was a reward and an acknowledgment of their severe depression. For those who were already considering rTMS treatment, paying for treatment was deemed unaffordable and the waiting time within the National Health Service (NHS) Trust where rTMS is available was too long. The study design itself was attractive due to the access to treatment in both arms so participants understood that taking part in the trial would guarantee some form of TMS treatment “because there wasn't an arm where you don't get treatment” (Participant 3). 3.1.2 Influence of staff This theme reflects the positive impact that staff had on participants’ experience which in turn supported their engagement in the main trial. Subthemes and supporting quotes are shown in Table 2 of supplementary material 7. Positive interactions and experience All staff came across as “wonderful, very professional and fully informed” (Participant 2) whilst also being “compassionate and very sensitive” (Participant 3) which contributed to patients feeling comfortable and knowing what to expect from the treatment. During sessions, interactions with other patients via quizzes, games, or discussions about shared interests improved the patients’ experience such that time went faster and the sessions were more pleasant. Overall, the staff made the daily commitment more acceptable. Reassurance about treatment Staff had an important role in reassuring participants about the treatment. Concerns and fears could be raised by participants and discussed freely with staff who listened and were able to provide appropriate reassurance which “allayed those fears” (Participant 3). Staff were accommodating and flexible during the sessions, making the patients feel at ease, relaxed, and okay about having to cancel the occasional appointment. As a result, the caring staff contributed to reducing stress and anxiety triggered by the treatment itself. One participant even likened the environment and attentiveness of staff to going to a spa. 3.1.3 Seeking relief from depression. Table 3 of supplementary material 7 shows the subthemes and supporting quotes. This theme reflects the shared experience of participants dealing with TRD, who, despite trying many different treatments before, continued to experience difficulties with everyday life. Desperation to try new treatment for depression The treatment-resistant nature of participants’ depression caused frustration but also a sense of desperation that meant they were willing to try any new treatment, even an experimental one, that might help relieve their symptoms . Most participants had a long history of various treatments and “multiple different medications” (Participant 2) they had taken for depression, but many reported that “nothing has ever changed” (Participant 5), and sometimes, their negative feelings were worsened by medication. Therefore, they were particularly open to non-pharmaceutical treatments. The chance to improve their quality of life made the treatment and trial appealing, even if they may have been pessimistic that the treatment may not work. The research process was seen as key to introducing new effective treatments for depression whilst also advancing the knowledge about depression. As participants were keen for new treatments to be introduced, they felt motivated to take part in the trial. Treatment with fewer side-effects The safety and non-invasive nature of the treatment added to the interest as the treatment was perceived as incurring fewer possible side effects than medications. Participants felt reassured after being told that they could resume their everyday roles and tasks after each session. The participants were accustomed to side effects from the antidepressant medications they had tried so there was an expectation of some side effects, but they were perceived as being minor compared to the potential benefits. Furthermore, the location of the treatment within the NHS sites ensured the availability of medical support in the event of an adverse event, and this provided reassurance and “made me feel very safe” (Participant 15) 3.1.4 Altruism Whilst participants were keen to join the study for the potential benefits to their own mental health, they also expressed an interest in wanting to help others in a similar situation. This altruism contributed to their decision to participate. Some felt that participating in the study would be useful even if the treatment was not effective for them. Quotes for this theme can be found in Table 4 of supplementary material 7. 3.2 Barriers Significant barriers to participation in the TMS treatment trial were reported such as commitment concerns stemming from the challenge of attending daily sessions for a month, which disrupted participants' routines and work schedules, particularly for those who were employed or dealing with poor health. Treatment-related concerns highlighted fears about potential side effects, especially in comparison to Electroconvulsive Therapy (ECT), and anxiety about the unknown sensations of the treatment, which together deterred some individuals from engaging in the trial. Barriers to taking part in the study were experienced by both those who were recruited and completed the treatments and those who declined to participate. For some, the barriers did not prevent engagement in the trial or the treatment. However, for others, those barriers and concerns outweighed the positives and potential benefits and led them to decide not to participate in the trial. 3.2.1 Commitment concerns Table 5 of supplementary material 7 outlines subthemes and supporting quotes. Having to attend daily sessions The treatment requirement of having to attend daily sessions for almost a month was a commitment that acted as a barrier to participation in the trial. The frequency of attendance was described as intense and requiring a new daily routine to be built around the treatment. With treatment sessions taking place at different times every day and only during business hours, fitting the sessions around work was difficult for participants who reported having to use annual leave and sick leave to attend. Therefore, the treatment was more accessible for those who were self-employed or not working. Even those who were retired described that the “commitment to attend for a period of days” (Participant 14) clashed with other commitments and was challenging. Concerns about attendance due to poor health In addition, there were also specific concerns about not being able to attend the daily sessions because of feeling too unwell due to their mental health, or because of common illnesses such as getting a cold, sickness bug, or COVID-19. This reflected difficulties with making daily commitments or leaving the house which are often described by those with depression and/or anxiety. Once out of the house, anxiety related to facing the prospect of commuting or finding parking was highlighted as a barrier, particularly in participants who were not comfortable with crowds or relying on public transport. These concerns were heightened during the COVID-19 pandemic when recruitment to the trial resumed after being closed for six months, when people were worried about mixing with others either on public transport or on NHS premises. 3.2.2 Treatment-related concerns Other concerns that acted as a barrier to participating in the trial were directly linked to the nature of the treatment. Table 5 of supplementary material 7 outlines subthemes and supporting quotes. Fear of side effects – comparison with ECT Participants drew comparisons between rTMS/cgiTBS and ECT and these associations triggered fears of potential side effects such as memory loss. In one of the trial sites, the location of the treatment room was next to the ECT suite which caused further anxiety and brought back negative memories for participants who previously received ECT or knew of people who had negative experiences of ECT. The comparison with ECT heightened concerns about the side effects of TMS which were feared to be memory loss and epileptic seizure, despite the comparative safety of the TMS treatment. The fact that participants were told that they would be able to drive back home after each treatment session reassured them as it emphasised that the treatment was non-invasive and side effects were unlikely. Not knowing what to expect Beyond the association with ECT, the uncertainty regarding sensations produced by the magnetic stimulation and the fear of pain caused anxiety and was a barrier to taking part. The fears seemed to be linked to the magnetic stimulation making direct changes to the brain which was perceived to be “quite a weird [idea]” (Participant 3). Some participants were concerned that the treatment could make their situation worse. 4. Discussion The study identified facilitators and barriers to taking part in TMS treatment as part of a clinical trial for those with TRD. Key facilitators were the hope that this treatment would prove effective in treating their own TRD and help others by taking part in the research to test new treatments, and staff providing reassurance and support throughout the recruitment and treatment processes. Acceptance of the TMS treatment being offered was rooted in the hope that it would help improve their depression symptoms and driven by the treatment-resistant nature of their depression and a history of unsuccessful or difficult-to-tolerate treatment experiences. These findings match the themes of “treatment resistance”, “side effects from other treatments” and “desperation for relief” found in the content analysis of emails from patients self-referring to TMS treatment (Clarke et al. , 2018), and confirms that participants with negative experiences of antidepressants through side effects or lack of effectiveness were more motivated to take part in new treatments (Huijbers et al. , 2020). Participants were keen to see new forms of treatment for depression with fewer side effects than medications, driving their interest in taking part in research. Whilst they were hoping for their own symptoms to improve, participants were also motivated to take part in the trial because it might have positive impacts on society by helping others with depression. Staff professionalism and the quality of their relationship with potential participants also affected the decision to take part. Researchers and clinicians made patients feel at ease, and comfortable to ask questions and share concerns. Staff reassurance through explaining TMS treatment and its non-invasive nature was a key facilitator as reported previously (Mallon et al. , 2020). The current study also shows that providing reassurance at the point of recruitment facilitates the decision to take part. Through reassurance and being approachable, clinicians have an important role in forming patients’ first impression of TMS through to the end of treatment. In previous studies in patients with chronic musculoskeletal pain, the first impression of TMS was identified as a decisive factor in accepting treatment, and lack of knowledge and understanding about treatment was the main barrier to TMS treatments (Stillianesis et al. , 2022). The main barriers to taking part in the trial were related to the commitment to the trial regime and the uncertainty around the nature of the treatment. In this trial, patients attended daily TMS sessions for four weeks. This expectation caused concerns as participants worried about not being able to leave their homes to attend sessions due to depression and anxiety. These emotional responses to the invitation to participate are likely to be bound up in the nature of the patient’s symptoms and levels of mood at the time. However, the interviewees who declined participation in the trial also commented on commitment issues related to work obligations. As such, the treatment seemed more accessible to those with more flexibility, such as the retired or self-employed. A few studies have explored accelerated TMS treatment whereby the 20-session delivery is condensed into one week (Baeken et al. , 2017; Caeyenberghs et al. , 2018; Cole et al. , 2020) which might significantly reduce the impact of the work commitment barrier. The experimental roots and novelty of the treatment also proved stressful for patients as they did not know what to expect from it, which was especially difficult for those who experienced comorbid anxiety. The concept of TMS evoked associations with ECT, which was negatively perceived due to known historically reported side effects, e.g. short-term memory loss, although TMS has been associated with improvements in working memory and attention (Brunoni and Vanderhasselt, 2014; Hauer et al. , 2019). 4.2. Research and clinical implications The findings in this study highlight the critical role of clinicians as facilitators of TMS for patients with TRD. Whilst being approachable and showing empathy, they should be prepared to explain the treatment to patients, reassure them about the side effects, and clarify the differences between TMS and ECT. Clinicians need to be able to describe the TMS sensation to patients and illustrate the treatment journey whilst monitoring patients’ expectations of the treatment. Some flexibility around the treatment schedule is key such that if patients cannot attend one session, another one can be booked within the treatment timeframe, which should be communicated to the patient before commencing treatment. Given the TMS commitment, availability might be an issue for patients with more rigid schedules (e.g., work). Offering treatment in the evening as an alternative will prove useful for patients. Alternatively, the effects of accelerated TMS treatment sessions delivered over one or two weeks might also be more feasible for the working population wanting to access TMS treatments (Tang, Shu and Wang, 2024). 4.3. Strengths and limitations A strength of the study is that we deliberately conducted the interviews and qualitative analysis before recruitment to this large multicentre trial had ended and without knowledge of the results of the trial. The main results of the BRIGhTMIND trial are now published, showing that the study was adequately powered with no difference between either treatment arm but a clinically substantial treatment effect of more than seven points with both forms of TMS on the primary outcome measure, the 17-item Hamilton Depression Rating Scale at 8, 16 and 26 weeks (Morriss et al. , 2024). There are several limitations to the study. Firstly, none of those who withdrew during or after the TMS treatment chose to take part. Such participants might have identified new barriers. Possible reasons for not choosing to talk about their experiences on the trial may relate to an unwillingness to be interviewed by the same researchers who enrolled them in the main trial. Future research should conduct the qualitative work independently of the main trial. Part of the trial took place during the COVID-19 pandemic. Whilst most of the interviews were conducted with participants who completed the treatment before the start of the pandemic, we interviewed three participants who received treatment after March 2020. These understandably highlighted commitment concerns as a barrier to recruitment. However, the same topic guide was used throughout so the specific effects of the COVID-19 pandemic on decision-making about participation in the trial or in TMS were not explored in depth. 5. Conclusions Taking part in a clinical trial of TMS treatment for those with TRD was facilitated by hope in the effectiveness of the treatment for their own and others’ symptoms and by reassuring and supportive clinical and research staff. The barriers to engaging with the trial were uncertainty about committing to attend daily sessions for four weeks and concerns about the nature of the treatment, particularly its perceived association with ECT. Declarations Credit authorship contribution statement Clement Boutry: Conducted interviews, analysed transcripts (coding), developed themes and subthemes, interpreted findings, and drafted the manuscript. Lucy Webster: Second-coded some of the transcripts, developed themes and subthemes, interpreted findings, reviewed the manuscript, liaised with patient involvement, and reviewed the manuscript. Louise Thomson: Designed and supervised analysis, interpreted findings, and supervised and reviewed manuscript writing. Peter Bates: Led the patient involvement group, reviewed the study design, interpreted findings, and reviewed the manuscript. Rebecca McNaughton, Joanne Ooi, Jane Eastham, John Gledhill, Andy Willis & Sonal Marner: Reviewed the study design, interpreted findings and reviewed the manuscript. Delilah Harding, & Isabel Reid: Conducted interviews and reviewed the manuscript. Richard Morriss: Chief investigator of the main trial, supervised the study, and drafted the manuscript. Declaration of Interest None Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. Magstim plc supplied TMS delivery and neuronavigation systems. Acknowledgements The authors thank the patient group for sharing valuable experiences and support in interpreting the findings. The authors also thank Jo Highman for conducting some of the interviews. Lastly, we would like to express our sincere gratitude to Professor Alex Kerr, Dr Mohamed Abdelghani, Professor Hamish McAllister-Williams, and Dr Sudheer Lankappa for their exceptional leadership and invaluable contributions to this research project. The views and opinions expressed by authors and interviewees in this publication are those of the authors and interviewees, and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the EME programme, the Department of Health or the Magstim company. Availability of Data and Materials The data are not publicly available because the participants do not consent to their data being shared. Ethics declarations The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving patients were approved by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. All participants were notified about their rights before interviewing and provided a consent to participate. Trial Registration Trial registration: ISRCTN19674644||http://www.isrctn.org/) registered on 01/10/2018. Trial Identifying numbers: CPMS 39297, IRAS 245025 References Baeken, C. et al. (2017) ‘Subgenual anterior cingulate–medial orbitofrontal functional connectivity in medication-resistant major depression: a neurobiological marker for accelerated intermittent theta burst stimulation treatment?’, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging , 2(7), pp. 556–565. Blumberger, D.M. et al. (2018) ‘Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial’, The Lancet , 391(10131), pp. 1683–1692. Available at: https://doi.org/10.1016/S0140-6736(18)30295-2. Brunoni, A.R. and Vanderhasselt, M.-A. (2014) ‘Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis’, Brain and Cognition , 86, pp. 1–9. Available at: https://doi.org/10.1016/j.bandc.2014.01.008. Bulteau, S. et al. (2022) ‘Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP)’, Brain Stimulation , 15(3), pp. 870–880. Available at: https://doi.org/10.1016/j.brs.2022.05.011. Caeyenberghs, K. et al. (2018) ‘Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: a connectome analysis’, Network Neuroscience , 3(1), pp. 157–172. Clarke, M. et al. (2018) ‘Patients with depression who self-refer for transcranial magnetic stimulation treatment: exploratory qualitative study’, BJPsych Bulletin , 42(6), pp. 243–247. Available at: https://doi.org/10.1192/bjb.2018.49. Cole, E.J. et al. (2020) ‘Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression’, American Journal of Psychiatry , 177(8), pp. 716–726. Available at: https://doi.org/10.1176/appi.ajp.2019.19070720. Fitzgerald, P.B., George, M.S. and Pridmore, S. (2022) ‘The evidence is in: Repetitive transcranial magnetic stimulation is an effective, safe and well-tolerated treatment for patients with major depressive disorder’, Australian & New Zealand Journal of Psychiatry , 56(7), pp. 745–751. Available at: https://doi.org/10.1177/00048674211043047. Gale, N.K. et al. (2013) ‘Using the framework method for the analysis of qualitative data in multi-disciplinary health research’, BMC medical research methodology , 13(1), pp. 1–8. Hauer, L. et al. (2019) ‘Effects of repetitive transcranial magnetic stimulation over prefrontal cortex on attention in psychiatric disorders: a systematic review’, Journal of clinical medicine , 8(4), p. 416. Available at: https://www.mdpi.com/2077-0383/8/4/416 (Accessed: 10 May 2024). Health Quality Ontario (2016) ‘Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials’, Ontario Health Technology Assessment Series , 16(5), pp. 1–66. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808719/ (Accessed: 17 March 2022). Huijbers, M.J. et al. (2020) ‘Discontinuing antidepressant medication after mindfulness-based cognitive therapy: a mixed-methods study exploring predictors and outcomes of different discontinuation trajectories, and its facilitators and barriers’, BMJ Open , 10(11), p. e039053. Available at: https://doi.org/10.1136/bmjopen-2020-039053. Kerr, C., Nixon, A. and Wild, D. (2010) ‘Assessing and demonstrating data saturation in qualitative inquiry supporting patient-reported outcomes research’, Expert review of pharmacoeconomics & outcomes research , 10(3), pp. 269–281. Larson, J. and Munkácsy, E. (2015) ‘Theta-burst LTP’, Brain Research , 1621, pp. 38–50. Available at: https://doi.org/10.1016/j.brainres.2014.10.034. Lincoln, Y. and Guba, E.G. (1985) ‘Lincoln, Yvonna, and Egon G. Guba, Naturalistic Inquiry. Beverly Hills, CA: Sage, 1985.’ Mallon, S. et al. (2020) ‘Practitioner perspectives on best practice in non-treatment factors that support the delivery of repetitive transcranial magnetic stimulation (rTMS) for depression’, Journal of Psychiatric and Mental Health Nursing , n/a(n/a). Available at: https://doi.org/10.1111/jpm.12815. Morriss, R. et al. (2020) ‘Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND)’, BMJ Open , 10(7), p. e038430. Available at: https://doi.org/10.1136/bmjopen-2020-038430. Morriss, R. et al. (2024) ‘Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial’, Nature Medicine , pp. 1–11. Available at: https://www.nature.com/articles/s41591-023-02764-z (Accessed: 10 May 2024). NICE:IPG542 (2015) Overview | Repetitive transcranial magnetic stimulation for depression | Guidance | NICE . NICE. Available at: https://www.nice.org.uk/guidance/ipg542 (Accessed: 17 March 2022). Nowell, L.S. et al. (2017) ‘Thematic Analysis: Striving to Meet the Trustworthiness Criteria’, International Journal of Qualitative Methods , 16(1), p. 1609406917733847. Available at: https://doi.org/10.1177/1609406917733847. Pszczolkowski, S. et al. (2022) ‘Connectivity-guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: magnetic resonance imaging protocol and SARS-CoV-2–induced changes for a randomized double-blind controlled trial’, JMIR Research Protocols , 11(1), p. e31925. Available at: https://www.researchprotocols.org/2022/1/e31925 (Accessed: 10 May 2024). Ritchie, J. and Spencer, L. (2002) ‘Qualitative data analysis for applied policy research’, in Analyzing qualitative data . Routledge, pp. 173–194. Available at: https://api.taylorfrancis.com/content/chapters/edit/download?identifierName=doi&identifierValue=10.4324/9780203413081-10&type=chapterpdf (Accessed: 10 May 2024). Stillianesis, G. et al. (2022) ‘Exploring patient perceptions of repetitive transcranial magnetic stimulation as a treatment for chronic musculoskeletal pain: a qualitative study’, BMJ Open , 12(8), p. e058928. Available at: https://doi.org/10.1136/bmjopen-2021-058928. Tang, N., Shu, W. and Wang, H. (2024) ‘Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief?’, WIREs Cognitive Science , 15(1), p. e1666. Available at: https://doi.org/10.1002/wcs.1666. Additional Declarations No competing interests reported. Supplementary Files BRIGHTMINDFBSupplementarymaterial.docx Cite Share Download PDF Status: Published Journal Publication published 25 Jul, 2025 Read the published version in BMC Psychiatry → Version 1 posted Editorial decision: Revision requested 25 Oct, 2024 Editor assigned by journal 25 Oct, 2024 Submission checks completed at journal 25 Oct, 2024 First submitted to journal 23 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5319588","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":370552014,"identity":"4cf8a323-71eb-43c6-b6be-696a5fb1c5df","order_by":0,"name":"Clement Boutry","email":"data:image/png;base64,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","orcid":"","institution":"University of Nottingham","correspondingAuthor":true,"prefix":"","firstName":"Clement","middleName":"","lastName":"Boutry","suffix":""},{"id":370552015,"identity":"26969893-21a8-4acb-95e0-b1ad41da0994","order_by":1,"name":"Lucy Webster","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Lucy","middleName":"","lastName":"Webster","suffix":""},{"id":370552016,"identity":"028fbf16-7547-4fe6-a0bb-4f8aa18907d8","order_by":2,"name":"Louise Thomson","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"prefix":"","firstName":"Louise","middleName":"","lastName":"Thomson","suffix":""},{"id":370552017,"identity":"7a2a33ee-a88b-4696-8050-085a7265f2ba","order_by":3,"name":"Delilah Harding","email":"","orcid":"","institution":"Camden and Islington NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Delilah","middleName":"","lastName":"Harding","suffix":""},{"id":370552018,"identity":"fd014c70-e276-4cd9-9402-a373202ba941","order_by":4,"name":"Isabel Reid","email":"","orcid":"","institution":"Berrywood Hospital, Northamptonshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Isabel","middleName":"","lastName":"Reid","suffix":""},{"id":370552019,"identity":"818b046d-d087-4c99-9692-ddecb270677e","order_by":5,"name":"Peter Bates","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Bates","suffix":""},{"id":370552020,"identity":"5391f7f8-caef-4eb4-941c-5d7a4e8a03a7","order_by":6,"name":"John Gledhill","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Gledhill","suffix":""},{"id":370552021,"identity":"625d2de8-ff6b-4533-bb13-b8c38ae878ff","order_by":7,"name":"Rebecca McNaughton","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Rebecca","middleName":"","lastName":"McNaughton","suffix":""},{"id":370552023,"identity":"fe376ca8-50b9-4b31-a48d-db1bc715a760","order_by":8,"name":"Jane Eastham","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Jane","middleName":"","lastName":"Eastham","suffix":""},{"id":370552025,"identity":"e19dcfab-ac66-425e-b2e3-c872f2e59425","order_by":9,"name":"Joanne Ooi","email":"","orcid":"","institution":"Camden and Islington NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Joanne","middleName":"","lastName":"Ooi","suffix":""},{"id":370552027,"identity":"9665ed0c-3043-447e-9a7f-56aad7a016f8","order_by":10,"name":"Andy Willis","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Andy","middleName":"","lastName":"Willis","suffix":""},{"id":370552028,"identity":"e61467f2-7a58-4352-8517-b7a049a998a9","order_by":11,"name":"Sonal Marner","email":"","orcid":"","institution":"Nottinghamshire Healthcare NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Sonal","middleName":"","lastName":"Marner","suffix":""},{"id":370552029,"identity":"1cb3de95-002b-447b-a5f1-903d5f1b6e91","order_by":12,"name":"Richard Morriss","email":"","orcid":"","institution":"University of Nottingham","correspondingAuthor":false,"prefix":"","firstName":"Richard","middleName":"","lastName":"Morriss","suffix":""}],"badges":[],"createdAt":"2024-10-23 14:08:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5319588/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5319588/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12888-025-06893-2","type":"published","date":"2025-07-25T15:58:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88506139,"identity":"2304c052-f52a-40a0-b4da-8633f093b972","added_by":"auto","created_at":"2025-08-07 07:31:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":862748,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5319588/v1/84c320ec-32b7-45df-9b58-dbd67fc7eb1e.pdf"},{"id":68287066,"identity":"3e9236c3-b0db-4977-8453-9c3bf0a19b32","added_by":"auto","created_at":"2024-11-05 16:24:06","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":43633,"visible":true,"origin":"","legend":"","description":"","filename":"BRIGHTMINDFBSupplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5319588/v1/b796204eaad56bd8b649bec6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Facilitators and barriers to participation of patients with treatment resistant depression in a randomised controlled trial of two forms of personalised magnetic resonance imaging targeted transcranial magnetic stimulation (the BRIGhTMIND trial)","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eTranscranial magnetic stimulation (TMS) is a National Institute for Health and Care Excellence (NICE) approved intervention using the application of magnetic pulse to change brain activity for both depression and treatment-resistant depression (TRD)\u0026nbsp;(NICE, 2015). However, it is still only available as a clinical intervention in a minority of mental health services in the UK and internationally. Repetitive TMS (rTMS) is the traditional form delivered at a standard site in 37.5-minute sessions on 20 or more occasions. \u0026nbsp;Benefits typically only last 1-3 months with a high degree of variability between individuals\u0026nbsp;(NICE, 2015; Health Quality Ontario, 2016).\u0026nbsp;Intermittent\u0026nbsp;theta burst stimulation (iTBS) is an alternative patterned form of TMS that mimics the brain’s natural electromagnetic rhythm producing long-term and therefore might be effective for a longer duration of time\u0026nbsp;(Larson and Munkácsy, 2015).\u0026nbsp;It is equally effective for treatment-resistant depression\u0026nbsp;(Blumberger \u003cem\u003eet al.\u003c/em\u003e, 2018; Bulteau \u003cem\u003eet al.\u003c/em\u003e, 2022; Morriss \u003cem\u003eet al.\u003c/em\u003e, 2024)\u0026nbsp;and requires a shorter duration of administration\u0026nbsp;(Blumberger \u003cem\u003eet al.\u003c/em\u003e, 2018), thereby increasing patient throughput in a clinical TMS service.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhilst evidence suggests that TMS in depression is generally well-tolerated\u0026nbsp;(Fitzgerald, George and Pridmore, 2022),\u0026nbsp;only a small number of studies have investigated the facilitators and barriers to accessing TMS treatments for depression or other conditions. Clinicians have been identified as having an important role in facilitating engagement in TMS. This role goes beyond just delivering TMS treatment to include engaging in constructive therapeutic conversations, providing a relaxing and friendly environment, and supportive long-term management\u0026nbsp;(Mallon \u003cem\u003eet al.\u003c/em\u003e, 2020; Stillianesis \u003cem\u003eet al.\u003c/em\u003e, 2022).\u0026nbsp;Patients’ initial impression of TMS and the equipment used to deliver it is thought to be a decisive factor, influencing both their perceptions of treatment effectiveness and also causing fear and apprehension in some\u0026nbsp;(Stillianesis \u003cem\u003eet al.\u003c/em\u003e, 2022).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhilst prior research provides some implications for practice guidance in engaging patients with rTMS, the facilitators and barriers to recruitment to a research trial offering rTMS or iTBS have not been explored.\u0026nbsp;We conducted qualitative interviews that ran parallel to the BRIGhTMIND study, a multi-site RCT in which patients with TRD received 20 sessions of either rTMS or connectivity-guided intermittent theta burst stimulation (cgiTBS), a form of iTBS\u0026nbsp;(Morriss \u003cem\u003eet al.\u003c/em\u003e, 2020, 2024; Pszczolkowski \u003cem\u003eet al.\u003c/em\u003e, 2022), to explore the barriers and facilitators to the recruitment of participants in the trial.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThe study employed a qualitative analysis of semi-structured interviews conducted with participants in the BRIGhTMIND trial. Ethical approval was provided by NHS Research Ethics Committee (ref: 18/EM/0232).\u0026nbsp;In the BRIGhTMIND trial, 255 participants with TRD were recruited. They were informed that we were testing two different forms of TMS treatment that were personalised using MRI scans and neuronavigation - \u0026nbsp;allowing for precise targeting of the coil placement area (rTMS versus cgiTBS), \u0026nbsp;to extend the duration of improvement in depression symptoms from 1-3 months to 6 months. They were to be randomised to one of these two treatments and they would need to attend a baseline assessment and MRI scan, complete 20 sessions of TMS over 4-6 weeks, have further clinical assessments at 8-, 16- and 26 weeks post randomisation, with a further MRI scan at 16 weeks. They were provided further information on potential adverse effects and details on the procedures involved in the trial. We provided materials showing how we approached clinicians and participants, including changes as a result of the COVID-19 pandemic, and our recruitment strategy (see supplementary material 1-4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1 Data Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree sets of participants were anticipated to be recruited to this study using purposive sampling: i) participants who completed TMS treatments were invited to participate after their 26-week follow-up assessment; ii) participants who withdrew from the main BRIGhTMIND trial during or after commencing TMS treatments – thus, did not complete the treatment course (i.e. withdrawn participants); and iii) participants who had returned a reply slip to the research team expressing interest in the main BRIGhTMIND trial, but declined to participate before being randomised (i.e. declined participants). Recruitment took place across four of the five UK NHS sites participating in the main trial.\u003c/p\u003e\n\u003cp\u003eEligible participants were sent an invitation letter, an information sheet\u0026nbsp;highlighting the aims and content of the study, a copy of the consent form, and a reply slip for the interview study.\u0026nbsp;Those that returned\u0026nbsp;reply slips expressing interest were contacted to schedule an interview,\u0026nbsp;conducted by researchers working on the main BRIGhTMIND clinical trial with experience in conducting qualitative interviews. Before the interview, the researcher reviewed the information sheet with the participants, who were then given the opportunity to ask questions, before giving consent to participate. Written consent was obtained for face-to-face interviews, and verbal consent was obtained and formally recorded for telephone interviews.\u0026nbsp;Interviews were recorded on an encrypted digital voice recorder and transcribed using a professional transcription service.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe interviews were conducted between October 2019 and March 2022 and lasted between eight and 26 minutes. Five were completed in person, whilst the remaining interviews were conducted remotely due to either participant preference or COVID-19 pandemic-related restrictions.\u003c/p\u003e\n\u003cp\u003eSemi-structured topic guides reviewed by a group of people with lived experience of TRD were used to explore\u0026nbsp;participants’ experiences of the facilitators and barriers to taking part in the BRIGhTMIND RCT which involved either receiving rTMS or cgiTBS\u0026nbsp;(Morriss \u003cem\u003eet al.\u003c/em\u003e, 2020). Topic guides included four broad questions: (1) how they found out about the trial; (2) their initial reaction on hearing about the trial and treatment involved; (3) the factors that motivated their decision about participation; (4) whether they had any concern about taking part in the trial. Participants who received TMS treatments as part of the main BRIGhTMIND trial\u0026nbsp;were also asked about their experience of the trial and the acceptability of the treatment, which will be reported in a separate paper. Topic guides can be found in the supplemental material 5 and 6.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of the 255 BRIGhTMIND trial participants, Nineteen were interviewed: seven from the Nottingham site, seven from the London site, three from the Northampton site, and two from the Newcastle site; aged 29-67 years (\u003cem\u003eM\u0026nbsp;\u003c/em\u003e= 49.7, \u003cem\u003eSD\u003c/em\u003e = 12.6 years). We did not recruit any participants from the Oldham site who joined the study after March 2022. The participants included ten males and nine females, with 17 (89.5%) white (British or other), and the remaining two participants of Asian or Asian British ethnicity. Eight (42.1%) participants were in full-time or other employment, seven (36.8%) were unemployed and four (21.1%) were retired. Fifteen (78.9%) of the interviewed participants had completed the full cycle of TMS treatments and follow-up assessments, and four (21.1%) had declined to participate in the trial before randomisation into treatments. None of the participants who withdrew from the trial during or after treatments returned the reply slips expressing an interest in this study. Of those that completed treatments, seven (36.8%) participants received rTMS treatment and eight (42.1%) received cgiTBS treatment. See Table 1 for more information.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Participants’ demographics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"491\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eService User ID Code\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eParticipation in trial\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment arm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNorthampton\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNorthampton\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNewcastle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNewcastle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDeclined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDeclined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDeclined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNorthampton\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDeclined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003en/a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCgi TBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNottingham\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ecgiTBS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eLondon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003erTMS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Data Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn inductive thematic framework analysis approach was used\u0026nbsp;(Ritchie and Spencer, 2002; Gale \u003cem\u003eet al.\u003c/em\u003e, 2013). Initially, transcripts were repeatedly read by two researchers (CB and LW) before coding, to allow researchers to familiarise and become immersed in the data before coding six of them separately\u0026nbsp;(Nowell \u003cem\u003eet al.\u003c/em\u003e, 2017), to ensure consistency and reliability of coding\u0026nbsp;(Lincoln and Guba, 1985). \u0026nbsp;One researcher (CB) coded the remaining 13 transcripts. The initial codes identified the interesting and most relevant features of the data, focused on the research objectives. Researchers (CB) and (LW) reached consensus that data had reached saturation as no new or meaningful codes emerged after 12 transcripts\u0026nbsp;(Kerr, Nixon and Wild, 2010), therefore, no additional interviews were required. However, after this, some further interviews were conducted to see if any new data was identified due to the COVID-19 pandemic. Following this, researchers (CB and LW) summarised the initial codes into broader categories. A discussion then took place with the principal investigator and qualitative lead (LT), whereby the overarching framework of themes was identified. The data was then input into the framework matrix using Nvivo 12. The research team scrutinised the final structure and codes which aided the refinement of the framework by renaming, merging/removing themes and sub-themes.\u003c/p\u003e\n\u003cp\u003eThe framework of themes and sub-themes were presented to the main trial’s patient and public involvement (PPI) group and then to researchers involved in the BRIGhTMIND study recruitment, for feedback and to support the interpretation of the findings. This allowed us to check the credibility of the analysis and results, further improving the trustworthiness of the results (Lincoln and Guba, 1985). The results were also used to inform the main trial’s ongoing recruitment and other procedures, demonstrating their transferability (Lincoln and Guba, 1985).\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThemes and sub-themes are summarised in Table 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Themes and sub-themes\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFacilitators\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBarriers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCommitment concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInfluence of staff\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTreatment-related concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInterest in new treatments\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAltruism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e3.1 Facilitators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants exhibited hope and optimism towards the innovative TMS treatment, driven by the desire for an effective alternative to medications. Positive interactions with compassionate and supportive staff, a desperate need for relief from TRD symptoms, and a sense of altruism towards helping others were key factors that motivated their participation and engagement in the trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.1 Hope\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary material 7, Table 1 shows the subthemes to the hope theme with supporting quotes.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eKeen to try alternative treatments\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParticipants’ enthusiasm\u0026nbsp;to get better\u0026nbsp;translated into openness towards the innovative treatment. There was optimism and hope that TMS treatments could help where other treatments had previously failed in relieving their depression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe positivity and hope stemmed from TMS being a different type of treatment option that targeted the cause of depression and “what physically happens to the brain rather than simply testing chemical levels” (Participant 14). Participants believed that this offered a credible alternative to pharmacological treatments.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGrateful for opportunity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParticipants also expressed feeling grateful and privileged that they were offered the opportunity to receive this treatment which affirmed an aspiration to get better. Participants felt glad that their symptoms made them eligible to access the treatment as if their participation was a reward and an acknowledgment of their severe depression.\u003c/p\u003e\n\u003cp\u003eFor those who were already considering rTMS treatment, paying for treatment was deemed unaffordable and the waiting time within the National Health Service (NHS) Trust where rTMS is available was too long.\u003c/p\u003e\n\u003cp\u003eThe study design itself was attractive due to the access to treatment in both arms so participants understood that taking part in the trial would guarantee some form of TMS treatment “because there wasn't an arm where you don't get treatment” (Participant 3).\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e3.1.2\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eInfluence of staff\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis theme reflects the positive impact that staff had on participants’ experience which in turn supported their engagement in the main trial. Subthemes and supporting quotes are shown in Table 2 of supplementary material 7.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePositive interactions and experience\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll staff came across as “wonderful, very professional and fully informed” (Participant 2) whilst also being “compassionate and very sensitive” (Participant 3) which contributed to patients feeling comfortable and knowing what to expect from the treatment.\u003c/p\u003e\n\u003cp\u003eDuring sessions, interactions with other patients via quizzes, games, or discussions about shared interests improved the patients’ experience such that time went faster and the sessions were more pleasant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall, the staff made the daily commitment more acceptable.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eReassurance about treatment\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eStaff had an important role in reassuring participants about the treatment. Concerns and fears could be raised by participants and discussed freely with staff who listened and were able to provide appropriate reassurance which “allayed those fears” (Participant 3).\u003c/p\u003e\n\u003cp\u003eStaff were accommodating and flexible during the sessions, making the patients feel at ease, relaxed, and okay about having to cancel the occasional appointment. As a result, the caring staff contributed to reducing stress and anxiety triggered by the treatment itself. One participant even likened the environment and attentiveness of staff to going to a spa.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.3 Seeking relief from depression.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 of supplementary material 7 shows the subthemes and supporting quotes. This theme reflects the shared experience of participants dealing with TRD, who, despite trying many different treatments before, continued to experience difficulties with everyday life.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDesperation to try new treatment for depression\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe treatment-resistant nature of participants’ depression caused frustration but also a sense of desperation that meant they were willing to try any new treatment, even an experimental one, that might help relieve their symptoms\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMost participants had a long history of various treatments and “multiple different medications” (Participant 2) they had taken for depression, but many reported that “nothing has ever changed” (Participant 5), and sometimes, their negative feelings were worsened by medication. Therefore, they were particularly open to non-pharmaceutical treatments.\u003c/p\u003e\n\u003cp\u003eThe chance to improve their quality of life made the treatment and trial appealing, even if they may have been pessimistic that the treatment may not work.\u0026nbsp;The research\u0026nbsp;process was seen as key to introducing new effective treatments for depression whilst also advancing the knowledge about depression. As participants were keen for new treatments to be introduced, they felt motivated to take part in the trial.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTreatment with fewer side-effects\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe safety and non-invasive nature of the treatment added to the interest as the treatment was perceived as incurring fewer possible side effects than medications. Participants felt reassured after being told that they could resume their everyday roles and tasks after each session.\u003c/p\u003e\n\u003cp\u003eThe participants were accustomed to side effects from the antidepressant medications they had tried so there was an expectation of some side effects, but they were perceived as being minor compared to the potential benefits. Furthermore, the location of the treatment within the NHS sites ensured the availability of medical support in the event of an adverse event, and this provided reassurance and “made me feel very safe” (Participant 15)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1.4 Altruism\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhilst participants were keen to join the study for the potential benefits to their own mental health, they also expressed an interest in wanting to help others in a similar situation. This altruism contributed to their decision to participate.\u0026nbsp;Some felt that participating in the study would be useful even if the treatment was not effective for them. Quotes for this theme can be found in Table 4 of supplementary material 7.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Barriers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSignificant barriers to participation in the TMS treatment trial were reported such as commitment concerns stemming from the challenge of attending daily sessions for a month, which disrupted participants' routines and work schedules, particularly for those who were employed or dealing with poor health. Treatment-related concerns highlighted fears about potential side effects, especially in comparison to Electroconvulsive Therapy (ECT), and anxiety about the unknown sensations of the treatment, which together deterred some individuals from engaging in the trial.\u003c/p\u003e\n\u003cp\u003eBarriers to taking part in the study were experienced by both those who were recruited and completed the treatments and those who declined to participate. For some, the barriers did not prevent engagement in the trial or the treatment. However, for others, those barriers and concerns outweighed the positives and potential benefits and led them to decide not to participate in the trial.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e\u0026nbsp;3.2.1 Commitment concerns\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eTable 5 of supplementary material 7 outlines subthemes and supporting quotes.\u003c/p\u003e\n\u003ch4\u003eHaving to attend daily sessions\u003c/h4\u003e\n\u003cp\u003eThe treatment requirement of having to attend daily sessions for almost a month was a commitment that acted as a barrier to participation in the trial. The frequency of attendance was described as intense and requiring a new daily routine to be built around the treatment.\u003c/p\u003e\n\u003cp\u003eWith treatment sessions taking place at different times every day and only during business hours, fitting the sessions around work was difficult for participants who reported having to use annual leave and sick leave to attend. Therefore, the treatment was more accessible for those who were self-employed or not working. Even those who were retired described that the “commitment to attend for a period of days” (Participant 14) \u0026nbsp; clashed with other commitments and was challenging.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003eConcerns about attendance due to poor health\u003c/h4\u003e\n\u003cp\u003eIn addition, there were also specific concerns about not being able to attend the daily sessions because of feeling too unwell due to their mental health, or because of common illnesses such as getting a cold, sickness bug, or COVID-19. This reflected difficulties with making daily commitments or leaving the house which are often described by those with depression and/or anxiety.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOnce out of the house, anxiety related to facing the prospect of commuting or finding parking was highlighted as a barrier, particularly in participants who were not comfortable with crowds or relying on public transport. These concerns were heightened during the COVID-19 pandemic when recruitment to the trial resumed after being closed for six months, when people were worried about mixing with others either on public transport or on NHS premises.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003e3.2.2 Treatment-related concerns\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eOther concerns that acted as a barrier to participating in the trial were directly linked to the nature of the treatment. Table 5 of supplementary material 7 outlines subthemes and supporting quotes.\u003c/p\u003e\n\u003ch4\u003eFear of side effects – comparison with ECT\u003c/h4\u003e\n\u003cp\u003eParticipants drew comparisons between rTMS/cgiTBS and ECT and these associations triggered fears of potential side effects such as memory loss. In one of the trial sites, the location of the treatment room was next to the ECT suite which caused further anxiety and brought back negative memories for participants who previously received ECT or knew of people who had negative experiences of ECT. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe comparison with ECT heightened concerns about the side effects of TMS\u0026nbsp;which were feared to be memory loss and epileptic seizure, despite the comparative safety of the TMS treatment. The fact that participants were told that they would be able to drive back home after each treatment session reassured them as it emphasised that the treatment was non-invasive and side effects were unlikely.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003eNot knowing what to expect\u003c/h4\u003e\n\u003cp\u003eBeyond the association with ECT, the uncertainty regarding sensations produced by the magnetic stimulation and the fear of pain caused anxiety and was a barrier to taking part.\u003c/p\u003e\n\u003cp\u003eThe fears seemed to be linked to the magnetic stimulation making direct changes to the brain which was perceived to be “quite a weird [idea]” (Participant 3). Some participants were concerned that the treatment could make their situation worse.\u0026nbsp;\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe study identified facilitators and barriers to taking part in TMS treatment as part of a clinical trial for those with TRD. Key facilitators were the hope that this treatment would prove effective in treating their own TRD and help others by taking part in the research to test new treatments, and staff providing reassurance and support throughout the recruitment and treatment processes. Acceptance of the TMS treatment being offered was rooted in the hope that it would help improve their depression symptoms and driven by the treatment-resistant nature of their depression and a history of unsuccessful or difficult-to-tolerate treatment experiences.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese findings match the themes of “treatment resistance”, “side effects from other treatments” and “desperation for relief” found in the content analysis of emails from patients self-referring to TMS treatment\u0026nbsp;(Clarke \u003cem\u003eet al.\u003c/em\u003e, 2018), and confirms that participants with negative experiences of antidepressants through side effects or lack of effectiveness were more motivated to take part in new treatments\u0026nbsp;(Huijbers \u003cem\u003eet al.\u003c/em\u003e, 2020).\u0026nbsp;Participants were keen to see new forms of treatment for depression with fewer side effects than medications, driving their interest in taking part in research. Whilst they were hoping for their own symptoms to improve, participants were also motivated to take part in the trial because it might have positive impacts on society by helping others with depression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStaff professionalism and the quality of their relationship with potential participants also affected the decision to take part. Researchers and clinicians made patients feel at ease, and comfortable to ask questions and share concerns. Staff reassurance through explaining TMS treatment and its non-invasive nature was a key facilitator as reported previously\u0026nbsp;(Mallon \u003cem\u003eet al.\u003c/em\u003e, 2020). The current study also shows that providing reassurance at the point of recruitment facilitates the decision to take part. Through reassurance and being approachable, clinicians have an important role in forming patients’ first impression of TMS through to the end of treatment. In previous studies in patients with chronic musculoskeletal pain, the first impression of TMS was identified as a decisive factor in accepting treatment, and lack of knowledge and understanding about treatment was the main barrier to TMS treatments\u0026nbsp;(Stillianesis \u003cem\u003eet al.\u003c/em\u003e, 2022).\u003c/p\u003e\n\u003cp\u003eThe main barriers to taking part in the trial were related to the commitment to the trial regime and the uncertainty around the nature of the treatment. In this trial,\u0026nbsp;patients attended daily TMS sessions for four weeks. This expectation caused concerns as participants worried about not being able to leave their homes to attend sessions due to depression and anxiety. These emotional responses to the invitation to participate are likely to be bound up in the nature of the patient’s symptoms and levels of mood at the time. However, the interviewees who declined participation in the trial also commented on commitment issues related to work obligations. As such, the treatment seemed more accessible to those with more flexibility, such as the retired or self-employed. A few studies have explored accelerated TMS treatment whereby the 20-session delivery is condensed into one week\u0026nbsp;(Baeken \u003cem\u003eet al.\u003c/em\u003e, 2017; Caeyenberghs \u003cem\u003eet al.\u003c/em\u003e, 2018; Cole \u003cem\u003eet al.\u003c/em\u003e, 2020)\u0026nbsp;which might significantly reduce the impact of the work commitment barrier.\u003c/p\u003e\n\u003cp\u003eThe experimental roots and novelty of the treatment also proved stressful for patients as they did not know what to expect from it, which was especially difficult for those who experienced comorbid anxiety. The concept of TMS evoked associations with ECT, which was negatively perceived due to known historically reported side effects, e.g. short-term memory loss, although TMS has been associated with improvements in working memory and attention\u0026nbsp;(Brunoni and Vanderhasselt, 2014; Hauer \u003cem\u003eet al.\u003c/em\u003e, 2019).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2. Research and clinical implications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings in this study highlight the critical role of clinicians as facilitators of TMS for patients with TRD. Whilst being approachable and showing empathy, they should be prepared to explain the treatment to patients, reassure them about the side effects, and clarify the differences between TMS and ECT. Clinicians need to be able to describe the TMS sensation to patients and illustrate the treatment journey whilst monitoring patients’ expectations of the treatment. Some flexibility around the treatment schedule is key such that if patients cannot attend one session, another one can be booked within the treatment timeframe, which should be communicated to the patient before commencing treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven the TMS commitment, availability might be an issue for patients with more rigid schedules (e.g., work). Offering treatment in the evening as an alternative will prove useful for patients. Alternatively, the effects of accelerated TMS treatment sessions delivered over one or two weeks might also be more feasible for the working population wanting to access TMS treatments\u0026nbsp;(Tang, Shu and Wang, 2024).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.3. Strengths and limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA strength of the study is that we deliberately conducted the interviews and qualitative analysis before recruitment to this large multicentre trial had ended and without knowledge of the results of the trial. The main results of the BRIGhTMIND trial are now published, showing that the study was adequately powered with no difference between either treatment arm but a clinically substantial treatment effect of more than seven points with both forms of TMS on the primary outcome measure, the 17-item Hamilton Depression Rating Scale at 8, 16 and 26 weeks\u0026nbsp;(Morriss \u003cem\u003eet al.\u003c/em\u003e, 2024).\u003c/p\u003e\n\u003cp\u003eThere are several limitations to the study. Firstly, none of those who withdrew during or after the TMS treatment chose to take part. Such participants might have identified new barriers. Possible reasons for not choosing to talk about their experiences on the trial may relate to an unwillingness to be interviewed by the same researchers who enrolled them in the main trial. Future research should conduct the qualitative work independently of the main trial.\u003c/p\u003e\n\u003cp\u003ePart of the trial took place during the COVID-19 pandemic. Whilst most of the interviews were conducted with participants who completed the treatment before the start of the pandemic, we interviewed three participants who received treatment after March 2020. These understandably highlighted commitment concerns as a barrier to recruitment. However, the same topic guide was used throughout so the specific effects of the COVID-19 pandemic on decision-making about participation in the trial or in TMS were not explored in depth.\u0026nbsp;\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eTaking part in a clinical trial of TMS treatment for those with TRD was facilitated by hope in the effectiveness of the treatment for their own and others\u0026rsquo; symptoms and by reassuring and supportive clinical and research staff.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe barriers to engaging with the trial were uncertainty about committing to attend daily sessions for four weeks and concerns about the nature of the treatment, particularly its perceived association with ECT.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCredit authorship contribution statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClement Boutry: Conducted interviews, analysed transcripts (coding), developed themes and subthemes, interpreted findings, and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eLucy Webster: Second-coded some of the transcripts, developed themes and subthemes, interpreted findings, reviewed the manuscript, liaised with patient involvement, and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eLouise Thomson: Designed and supervised analysis, interpreted findings, and supervised and reviewed manuscript writing.\u003c/p\u003e\n\u003cp\u003ePeter Bates: Led the patient involvement group, reviewed the study design, interpreted findings, and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eRebecca McNaughton, Joanne Ooi, Jane Eastham, John Gledhill, Andy Willis \u0026amp; Sonal Marner: Reviewed the study design, interpreted findings and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eDelilah Harding, \u0026amp; Isabel Reid: Conducted interviews and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eRichard Morriss: Chief investigator of the main trial, supervised the study, and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. Magstim plc supplied TMS delivery and neuronavigation systems.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patient group for sharing valuable experiences and support in interpreting the findings. The authors also thank Jo Highman for conducting some of the interviews. Lastly, we would like to express our sincere gratitude to Professor Alex Kerr, Dr Mohamed Abdelghani, Professor Hamish McAllister-Williams, and Dr Sudheer Lankappa for their exceptional leadership and invaluable contributions to this research project. The views and opinions expressed by authors and interviewees in this publication are those of the authors and interviewees, and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the EME programme, the Department of Health or the Magstim company.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data are not publicly available because the participants do not consent to their data being shared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving patients were approved by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. All participants were notified about their rights before interviewing and provided a consent to participate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTrial registration: ISRCTN19674644||http://www.isrctn.org/) registered on 01/10/2018.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTrial Identifying numbers: CPMS 39297, IRAS 245025\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBaeken, C. \u003cem\u003eet al.\u003c/em\u003e (2017) \u0026lsquo;Subgenual anterior cingulate\u0026ndash;medial orbitofrontal functional connectivity in medication-resistant major depression: a neurobiological marker for accelerated intermittent theta burst stimulation treatment?\u0026rsquo;, \u003cem\u003eBiological Psychiatry: Cognitive Neuroscience and Neuroimaging\u003c/em\u003e, 2(7), pp. 556\u0026ndash;565.\u003c/li\u003e\n\u003cli\u003eBlumberger, D.M. \u003cem\u003eet al.\u003c/em\u003e (2018) \u0026lsquo;Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial\u0026rsquo;, \u003cem\u003eThe Lancet\u003c/em\u003e, 391(10131), pp. 1683\u0026ndash;1692. Available at: https://doi.org/10.1016/S0140-6736(18)30295-2.\u003c/li\u003e\n\u003cli\u003eBrunoni, A.R. and Vanderhasselt, M.-A. (2014) \u0026lsquo;Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis\u0026rsquo;, \u003cem\u003eBrain and Cognition\u003c/em\u003e, 86, pp. 1\u0026ndash;9. Available at: https://doi.org/10.1016/j.bandc.2014.01.008.\u003c/li\u003e\n\u003cli\u003eBulteau, S. \u003cem\u003eet al.\u003c/em\u003e (2022) \u0026lsquo;Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP)\u0026rsquo;, \u003cem\u003eBrain Stimulation\u003c/em\u003e, 15(3), pp. 870\u0026ndash;880. Available at: https://doi.org/10.1016/j.brs.2022.05.011.\u003c/li\u003e\n\u003cli\u003eCaeyenberghs, K. \u003cem\u003eet al.\u003c/em\u003e (2018) \u0026lsquo;Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: a connectome analysis\u0026rsquo;, \u003cem\u003eNetwork Neuroscience\u003c/em\u003e, 3(1), pp. 157\u0026ndash;172.\u003c/li\u003e\n\u003cli\u003eClarke, M. \u003cem\u003eet al.\u003c/em\u003e (2018) \u0026lsquo;Patients with depression who self-refer for transcranial magnetic stimulation treatment: exploratory qualitative study\u0026rsquo;, \u003cem\u003eBJPsych Bulletin\u003c/em\u003e, 42(6), pp. 243\u0026ndash;247. Available at: https://doi.org/10.1192/bjb.2018.49.\u003c/li\u003e\n\u003cli\u003eCole, E.J. \u003cem\u003eet al.\u003c/em\u003e (2020) \u0026lsquo;Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression\u0026rsquo;, \u003cem\u003eAmerican Journal of Psychiatry\u003c/em\u003e, 177(8), pp. 716\u0026ndash;726. Available at: https://doi.org/10.1176/appi.ajp.2019.19070720.\u003c/li\u003e\n\u003cli\u003eFitzgerald, P.B., George, M.S. and Pridmore, S. (2022) \u0026lsquo;The evidence is in: Repetitive transcranial magnetic stimulation is an effective, safe and well-tolerated treatment for patients with major depressive disorder\u0026rsquo;, \u003cem\u003eAustralian \u0026amp; New Zealand Journal of Psychiatry\u003c/em\u003e, 56(7), pp. 745\u0026ndash;751. Available at: https://doi.org/10.1177/00048674211043047.\u003c/li\u003e\n\u003cli\u003eGale, N.K. \u003cem\u003eet al.\u003c/em\u003e (2013) \u0026lsquo;Using the framework method for the analysis of qualitative data in multi-disciplinary health research\u0026rsquo;, \u003cem\u003eBMC medical research methodology\u003c/em\u003e, 13(1), pp. 1\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eHauer, L. \u003cem\u003eet al.\u003c/em\u003e (2019) \u0026lsquo;Effects of repetitive transcranial magnetic stimulation over prefrontal cortex on attention in psychiatric disorders: a systematic review\u0026rsquo;, \u003cem\u003eJournal of clinical medicine\u003c/em\u003e, 8(4), p. 416. Available at: https://www.mdpi.com/2077-0383/8/4/416 (Accessed: 10 May 2024).\u003c/li\u003e\n\u003cli\u003eHealth Quality Ontario (2016) \u0026lsquo;Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials\u0026rsquo;, \u003cem\u003eOntario Health Technology Assessment Series\u003c/em\u003e, 16(5), pp. 1\u0026ndash;66. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808719/ (Accessed: 17 March 2022).\u003c/li\u003e\n\u003cli\u003eHuijbers, M.J. \u003cem\u003eet al.\u003c/em\u003e (2020) \u0026lsquo;Discontinuing antidepressant medication after mindfulness-based cognitive therapy: a mixed-methods study exploring predictors and outcomes of different discontinuation trajectories, and its facilitators and barriers\u0026rsquo;, \u003cem\u003eBMJ Open\u003c/em\u003e, 10(11), p. e039053. Available at: https://doi.org/10.1136/bmjopen-2020-039053.\u003c/li\u003e\n\u003cli\u003eKerr, C., Nixon, A. and Wild, D. (2010) \u0026lsquo;Assessing and demonstrating data saturation in qualitative inquiry supporting patient-reported outcomes research\u0026rsquo;, \u003cem\u003eExpert review of pharmacoeconomics \u0026amp; outcomes research\u003c/em\u003e, 10(3), pp. 269\u0026ndash;281.\u003c/li\u003e\n\u003cli\u003eLarson, J. and Munk\u0026aacute;csy, E. (2015) \u0026lsquo;Theta-burst LTP\u0026rsquo;, \u003cem\u003eBrain Research\u003c/em\u003e, 1621, pp. 38\u0026ndash;50. Available at: https://doi.org/10.1016/j.brainres.2014.10.034.\u003c/li\u003e\n\u003cli\u003eLincoln, Y. and Guba, E.G. (1985) \u0026lsquo;Lincoln, Yvonna, and Egon G. Guba, Naturalistic Inquiry. Beverly Hills, CA: Sage, 1985.\u0026rsquo;\u003c/li\u003e\n\u003cli\u003eMallon, S. \u003cem\u003eet al.\u003c/em\u003e (2020) \u0026lsquo;Practitioner perspectives on best practice in non-treatment factors that support the delivery of repetitive transcranial magnetic stimulation (rTMS) for depression\u0026rsquo;, \u003cem\u003eJournal of Psychiatric and Mental Health Nursing\u003c/em\u003e, n/a(n/a). Available at: https://doi.org/10.1111/jpm.12815.\u003c/li\u003e\n\u003cli\u003eMorriss, R. \u003cem\u003eet al.\u003c/em\u003e (2020) \u0026lsquo;Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND)\u0026rsquo;, \u003cem\u003eBMJ Open\u003c/em\u003e, 10(7), p. e038430. Available at: https://doi.org/10.1136/bmjopen-2020-038430.\u003c/li\u003e\n\u003cli\u003eMorriss, R. \u003cem\u003eet al.\u003c/em\u003e (2024) \u0026lsquo;Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial\u0026rsquo;, \u003cem\u003eNature Medicine\u003c/em\u003e, pp. 1\u0026ndash;11. Available at: https://www.nature.com/articles/s41591-023-02764-z (Accessed: 10 May 2024).\u003c/li\u003e\n\u003cli\u003eNICE:IPG542 (2015) \u003cem\u003eOverview | Repetitive transcranial magnetic stimulation for depression | Guidance | NICE\u003c/em\u003e. NICE. Available at: https://www.nice.org.uk/guidance/ipg542 (Accessed: 17 March 2022).\u003c/li\u003e\n\u003cli\u003eNowell, L.S. \u003cem\u003eet al.\u003c/em\u003e (2017) \u0026lsquo;Thematic Analysis: Striving to Meet the Trustworthiness Criteria\u0026rsquo;, \u003cem\u003eInternational Journal of Qualitative Methods\u003c/em\u003e, 16(1), p. 1609406917733847. Available at: https://doi.org/10.1177/1609406917733847.\u003c/li\u003e\n\u003cli\u003ePszczolkowski, S. \u003cem\u003eet al.\u003c/em\u003e (2022) \u0026lsquo;Connectivity-guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: magnetic resonance imaging protocol and SARS-CoV-2\u0026ndash;induced changes for a randomized double-blind controlled trial\u0026rsquo;, \u003cem\u003eJMIR Research Protocols\u003c/em\u003e, 11(1), p. e31925. Available at: https://www.researchprotocols.org/2022/1/e31925 (Accessed: 10 May 2024).\u003c/li\u003e\n\u003cli\u003eRitchie, J. and Spencer, L. (2002) \u0026lsquo;Qualitative data analysis for applied policy research\u0026rsquo;, in \u003cem\u003eAnalyzing qualitative data\u003c/em\u003e. Routledge, pp. 173\u0026ndash;194. Available at: https://api.taylorfrancis.com/content/chapters/edit/download?identifierName=doi\u0026amp;identifierValue=10.4324/9780203413081-10\u0026amp;type=chapterpdf (Accessed: 10 May 2024).\u003c/li\u003e\n\u003cli\u003eStillianesis, G. \u003cem\u003eet al.\u003c/em\u003e (2022) \u0026lsquo;Exploring patient perceptions of repetitive transcranial magnetic stimulation as a treatment for chronic musculoskeletal pain: a qualitative study\u0026rsquo;, \u003cem\u003eBMJ Open\u003c/em\u003e, 12(8), p. e058928. Available at: https://doi.org/10.1136/bmjopen-2021-058928.\u003c/li\u003e\n\u003cli\u003eTang, N., Shu, W. and Wang, H. (2024) \u0026lsquo;Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief?\u0026rsquo;, \u003cem\u003eWIREs Cognitive Science\u003c/em\u003e, 15(1), p. e1666. Available at: https://doi.org/10.1002/wcs.1666.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Transcranial magnetic stimulation, treatment-resistant depression, magnetic resonance imaging, study recruitment","lastPublishedDoi":"10.21203/rs.3.rs-5319588/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5319588/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground. \u003c/strong\u003eMagnetic resonance imaging (MRI) can personalise the site of transcranial magnetic stimulation (TMS) delivered as a course of 20 sessions for treatment-resistant depression (TRD). Facilitators and barriers to a randomised controlled trial (RCT) of MRI personalised TMS is understudied.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim. \u003c/strong\u003eTo explore facilitators and barriers behind RCT participants’ experience of personalised MRI-targeted TMS in people with TRD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods. \u003c/strong\u003eNineteen participants from the BRIGhTMIND RCT of two forms of MRI personalised TMS, completed semi-structured interviews exploring the reasons behind the uptake and experience of TMS. The sample included fifteen participants who completed the treatment course and four who declined to proceed before randomisation. Interviews were analysed using thematic analysis, co-produced between researchers and patients and public involvement contributors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e. Facilitators were “hope” regarding the treatment itself, the influence of research staff, interest in a new treatment, and altruism. Barriers were concerns about their ability to commit to the trial and the nature of the TMS itself. MRI was neither a facilitator nor a barrier to TMS. Throughout the themes, clinicians and researchers made a difference by explaining and setting realistic expectations of the treatment and building rapport through daily patient contact. The ability to offer TMS outside office hours would be a great advantage for patients in employment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion.\u003c/strong\u003eThe study highlights the importance of understanding patients’ concepts and experiences of TMS. The provision of optimal information to patients and the most efficacious, acceptable regimes of TMS delivery may maximise participation (Trial registration number ISRCTN19674644).\u003c/p\u003e","manuscriptTitle":"Facilitators and barriers to participation of patients with treatment resistant depression in a randomised controlled trial of two forms of personalised magnetic resonance imaging targeted transcranial magnetic stimulation (the BRIGhTMIND trial)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-05 16:23:54","doi":"10.21203/rs.3.rs-5319588/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-25T21:07:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-25T11:23:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-25T11:05:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2024-10-23T14:03:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"641d572a-37b9-45e6-b91a-0d44698b845d","owner":[],"postedDate":"November 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T07:19:07+00:00","versionOfRecord":{"articleIdentity":"rs-5319588","link":"https://doi.org/10.1186/s12888-025-06893-2","journal":{"identity":"bmc-psychiatry","isVorOnly":false,"title":"BMC Psychiatry"},"publishedOn":"2025-07-25 15:58:21","publishedOnDateReadable":"July 25th, 2025"},"versionCreatedAt":"2024-11-05 16:23:54","video":"","vorDoi":"10.1186/s12888-025-06893-2","vorDoiUrl":"https://doi.org/10.1186/s12888-025-06893-2","workflowStages":[]},"version":"v1","identity":"rs-5319588","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5319588","identity":"rs-5319588","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}