Improving access to gut‐directed hypnotherapy for irritable bowel syndrome in the digital therapeutics' era: Are mobile applications a “smart” solution?

Gut‐directed hypnotherapy (GDH) is a highly effective brain‐gut behavioral therapy which is recommended in international guidelines for the treatment of irritable bowel syndrome (IBS). There is increasing recognition of the value of GDH as part of integrated care alongside medical and dietary approaches. This has led to recent innovations to widen access to GDH to meet the increasing demand. Recent advances include streamlined courses of individualized GDH, group therapy, and remote delivery. In this issue of Neurogastroenterology and Motility, Peters et al. retrospectively report outcomes of smartphone app‐delivered GDH in a population with self‐reported IBS. While adherence was low, those that completed smart phone‐delivered GDH‐achieved symptom benefit. This mini‐review summarizes the current evidence‐base for available modalities of GDH and discusses the current and future utility and development of mobile health applications in the digital therapeutics' era.


| INTRODUC TI ON
Irritable bowel syndrome (IBS) is a highly prevalent disorder of gutbrain interaction (DGBI) worldwide with an estimated global prevalence of around 4%, 1 and is associated with significant impairment on quality-of-life, 2 increased healthcare utilization, 3 and high rates of patient reported stigmatization. 4 Given the extent of the population prevalence of IBS, the socioeconomic impact is considerable, 5 with annual healthcare costs estimated to be between £1.3 and £2 billion in the United Kingdom alone, 6 highlighting the need for new, innovative, and more cost-effective treatment strategies.
Gut-directed hypnotherapy (GDH) is an established braingut behavioral therapy with proven efficacy in clinical trials, 7 and is recommended widely for the treatment of IBS. [8][9][10] While there are no direct head-to-head comparative studies of brain-gut behavioral therapies for IBS, according to trial based meta-analyses, therapist-delivered GDH is one of the interventions with the strongest evidence-base, and is one of the few interventions with proven efficacy in refractory IBS. 7 While the exact mechanisms are not fully understood, GDH has been shown to induce appreciable changes in gastrointestinal function and physiology. In patients with IBS, GDH has been shown to modulate colonic motility and visceral sensitivity immediately after intervention. [11][12][13][14][15] Moreover, functional brain imaging studies suggest that hypnotherapy may modulate neuroplasticity and gut-brain interactions by modulating activity in brain regions involved with visceral afferent and pain pathways including the anterior cingulate cortex [16][17][18][19] prefrontal, insular, and somatosensory regions, 20 and posterior insula. 21,22 Not only has individualized, therapist-delivered GDH been shown to have response rates of around 75%, 23,24 its effects have shown to be long-lasting, [25][26][27] with wider socioeconomic benefits. 28 There is also evidence that early intervention with GDH in children and adolescents may reduce the burden of the condition in transition to adulthood. 29,30 Recently, the potential socioeconomic benefits of improving access to GDH has been highlighted in a landmark clinical trial which demonstrated that integrated multidisciplinary care including GDH achieves superior outcomes to gastroenterologist only care, with lower financial costs per successful outcome. 31 In the current climate, with greater understanding of the socioeconomic impacts and burden of IBS in resource stretched healthcare systems, there is now increasing interest in improving access to GDH.
Recent developments in improving access to GDH have included trial data which have confirmed that shorter courses of individualized GDH with six-sessions have non-inferior outcomes to 12-sessions, meaning that the throughput of a single therapist or department could be effectively doubled without altering outcomes.
There is also recent evidence that group-GDH can be just as effective as individualized therapy in primary and secondary care patients with IBS. 32,33 The group approach therefore allows greater access to GDH, potentially allowing individualized therapy to be reserved for those with more complex, and refractory forms of IBS in tertiary care, which are likely to require an individualized approach. Finally, remote, individualized GDH, delivered by a therapist via video has been shown to have comparable results to face-to-face therapy, 34 which has also improved access and is also potentially more costeffective to deliver.
In this context, in this edition of Neurogastroenterology and Motility, Peters et al. 35 have reported outcomes of a self-directed GDH skills training program delivered by a novel smartphone application (Nerva) in people with self-reported IBS. This data have given an important insight into the potential of smartphone GDH applications for IBS and will inform future studies to develop the utility to this type of technology further. The most important take home from this real-world study is that the overwhelming majority of those with self-reported IBS that downloaded and commenced the smartphone application failed to complete the treatment package (2590, 91%). In the participants that completed the smartphone GDH package and had outcome measures available, 64% achieved a 30% or greater improvement in abdominal pain severity, suggesting that this intervention may have potential for IBS and should be studied further. 35 In this mini review we discuss the fundamental differences between therapist-delivered individualized, group sessions, face-toface, and remote via video technologies, and the novel approach with digital therapeutics. We will cover the advantages and disadvantages of each modality of GDH delivery and discuss the implica-

| THE D IFFEREN CE S B E T WEEN D I G ITAL THER APEUTIC S AND THER APIS T-DELIVERED G UT-D IREC TED HYPNOTHER APY
Individualized GDH delivered by a trained therapist either face-toface or remotely via video consultation is a highly versatile treatment which can be tailored to a patient's symptom profile and personal imagery of their IBS. 36 The aims of GDH are to induce a deep state of relaxation to guide the patient to learn to control their gut function. Individualized therapy allows the therapist to use metaphors and hypnotic suggestions based upon the patients reported visual imagery. The treatment often follows a detailed hypnotherapeutic analysis during an introductory session with the therapist. 37 The introductory session enables the therapist to understand impact of IBS on their quality of life, including home, social, and education or work life. This first session is also an opportunity for the therapist to explain how the gut functions, often using diagrams and drawings. In young children and adolescents, the therapist will often identify hobbies and interests the patient has, for example, favorite stories, toys, games, sport, and nature so that these can be incorporated into the treatment to enhance their experience and improve engagement. 29 Group GDH delivered by a therapist teaches the same principles and techniques to induce a deep state of relaxation and hypnotic suggestions to influence gut function; however, the content of the sessions and metaphors used are inevitably more generic. In contrast to therapist-delivered GDH which is a therapeutic intervention, the smartphone application-delivered approach is a self-management tool to provide and teach self-hypnosis skills training to people with IBS using generic, scripted, hypnotherapy recordings. 35 The differences between therapist and smart phone-delivered approaches to GDH are summarized in Table 1. One of the main differences in smartphone-delivered hypnotherapy is the lack of guidance and input from a trained therapist, without the opportunity for an introductory session to customize the therapeutic approach, and the lack of feedback to and from the patient during and in between sessions.
This may contribute to the consistently high attrition rates that have been reported with self-directed online approaches to teaching behavioral self-management techniques for IBS, 35,38,39 and this should be taken into consideration in the design of future smartphone application studies with a focus on implementing interventions to optimize compliance.
Finally, another important role of the therapy team in GDH is patient selection. It is recognized that not all patients with disorders of gut-brain interaction are suitable for brain-gut behavioral therapies such as GDH. 36 Those with severe psychopathology, minimal insight into gut-brain connections, those overly focused on "cure", and those who cannot invest time, are considered to be inappropriate candidates for brain-gut behavioral therapies according to recent consensus recommendations from the Rome Foundation. 40 Hence, without careful patient selection it is likely that the lower adherence rates observed with self-directed approaches such as smartphone applications could be contributed to by enrolment of participants that are inappropriate candidates from the outset. This does raise the question whether smartphone GDH application use should be clinically prescribed in the future to ensure that the most appropriate candidates are selected. Clinician initiation would ensure that the diagnosis of IBS is clinically secure prior to commencement of the self-directed GDH intervention. Moreover, it is known that patients with IBS are often skeptical about GDH at the beginning of treatment. 41 Therefore, the benefit of clinician initiation (or prescription) of GDH smartphone applications would address this barrier by allowing the provider to communicate the rationale for brain-gut behavioral therapies such as GDH. As previously reported by patients in a survey of their views on a web-based self-directed cognitive behavioral therapy (CBT) intervention for IBS, 42 the clinician's input is likely to encourage engagement and compliance, especially when a digital therapeutic is self-directed.

| FUTURE D IREC TI ON S ON THE P OTENTIAL , UTILIT Y, AND DE VELOPMENT OF D I G ITAL THER APEUTI C S FOR G UT-DIREC TED HYPNOTHER APY
In the quest to make healthcare accessible, and affordable for patients digital therapeutics, including virtual reality (VR) using smartphones, and desktop computers, 43 designed to prevent, treat, and manage digestive health conditions, is an exciting new area in neurogastroenterology with considerable potential. However, as the number of different applications and platforms is burgeoning it is essential to control the quality and standard of care provided and to ensure patient safety.
The main purpose of developing such applications is to extend the reach of trained clinicians by overcoming constraints due to time, place, and manpower that limit the delivery of healthcare, thus improving access, convenience, and efficiency. However, whether the intervention is designed for the treatment of any physical or mental health condition, the developers need to make sure that an element of human contact is maintained as it is an essential component for healthcare delivery.
In the post COVID-19 era there is a demand for remotely delivered GDH as evidenced in a recent survey of patients with IBS in tertiary care where 52% of patients indicated a preference for remote telehealth delivery of individualized therapy. 44 However, a future study should examine if there is a similar demand for appbased, pre-recorded materials.
There are several advantages and disadvantages of self-directed smartphone delivery of GDH skills training which we have summarized in Table 2. While the efficacy of smartphone-delivered GDH in comparison to therapist-delivered GDH has not been previously studied and should be the subject of future research, smartphone GDH may have a role in teaching hypnotherapy skills to those with IBS. This might be particularly important where access to gastropsychologists and brain-gut behavioral therapists is lacking. As IBS has a high worldwide prevalence, 45 digital options may have an important future role in reducing disparities in the approach to IBS around the world, 46 for example by providing access to hypnotherapy skills for IBS sufferers in Asian countries where GDH services are likely to be of benefit, but not yet developed. 47,48 In preparation for this, smartphone applications with hypnotherapy recordings available in different languages would be required.
While smartphone-delivered GDH is an exciting and promising development, it is important that its utility is studied with the same rigors as therapist-delivered GDH to prove its efficacy in randomized controlled trials. Given the important differences between the two approaches already highlighted in Table 1, it would not be appropriate to extrapolate the data from trials in therapist-delivered GDH for smartphone applications. Moreover, it is likely that patients fulfilling Rome IBS criteria included in previously published randomized trials of clinician administered GDH in tertiary care settings would have a much higher baseline IBS severity. Therefore, clinical trials confirming short-and long-term efficacy of smartphone- The differences between therapist-delivered gut-directed hypnotherapy (GDH) and smartphone-delivered self-directed GDH skills training.

Therapist-delivered GDH Smartphone-delivered GDH skills training
Clinically proven efficacy in trials Efficacy unknown, needs further study Can be customized and personalized following initial consultation/ analysis Generic approach -regardless of need, requirement, and severity of symptoms.
Good compliance with low drop-out rate Concerns about poor adherence Rapport, feedback, and encouragement from a trained therapist Self-directed learning without any feedback or therapeutic interaction Often reserved for refractory cases due to associated costs and availability May be accessible option for patients with mild or moderate IBS Careful clinical patient selection process Risk of patients unsuitable for GDH/ less likely to benefit accessing online attrition rate in smartphone-delivered GDH skills training 35 was found to be higher than the reported drop-out rate for individualized, face-to-face GDH. 24 The reasons for such high attrition rates requires further study along with the implementation of interventions to improve completion rates. As discussed earlier, potential Interestingly, in the Peters et al. study, older patients and those that had tried a probiotic were more likely to respond, 35 and it may be that these sub-groups were more motivated, had tried more therapies over time, were therefore more likely to engage with and edit the manuscript and is the guarantor.