A self-guided smartphone hypnotherapy program did not meet the prespecified threshold for noninferiority to in-person hypnotherapy for abdominal pain response in patients with irritable bowel syndrome (IBS), according to findings published in Gut.
At weeks 13-16, Food and Drug Administration-defined abdominal pain response rates were 48.1% with in-person therapist-delivered hypnotherapy, 33.3% with smartphone-based self-guided hypnotherapy, and 21.8% with online psychoeducation. The response-rate difference between smartphone and in-person hypnotherapy was –14.7 percentage points (95% CI, –29.3 to 0.9). Because the lower confidence bound crossed the prespecified –10% noninferiority margin, noninferiority was not established.
In an interview with GI & Hepatology News, study investigator Daniel Keszthelyi, MD, PhD, of the Department of Gastroenterology and Hepatology at Maastricht University Medical Centre+ and Maastricht University, said gut-directed hypnotherapy should be considered earlier in IBS care.
“Gut-directed hypnotherapy has traditionally been considered a therapeutic entity for patients with IBS who had not experienced sufficient symptom resolution to other traditional treatments including dietary adjustment, such as the low-FODMAP diet, or drugs, like antispasmodics, yet it ought to be considered as first-line therapy,” Dr. Keszthelyi said.
He said this is particularly relevant because hypnotherapy “practically has no side effects.” However, broader use has been limited by the availability of trained professionals and reimbursement issues, which may lead patients or clinicians to choose other therapies.
Trial compared three delivery approaches
The multicenter, three-arm randomized controlled trial included 230 patients aged 17-73 years with Rome IV IBS. Mean age was 38.2 years, 70.4% were female, 47.0% were treated in primary care, and most had moderate or severe IBS symptom severity at baseline.
Patients were randomly assigned to 12 weeks of online self-guided psychoeducation, smartphone-based self-guided hypnotherapy, or in-person therapist-delivered hypnotherapy.
In-person treatment consisted of six biweekly 45-minute sessions using a structured hypnotherapy protocol, plus home exercises for 15-30 minutes per day on five days each week. The smartphone group received the same scripted hypnotherapy sessions through audio delivered by an app and was instructed to use the program for 15-30 minutes per day on five days each week. The psychoeducation group completed interactive online self-guided modules designed to support IBS self-management.
The primary endpoint was abdominal pain response by FDA criteria, defined as at least a 30% reduction from baseline in the weekly average of worst daily abdominal pain during at least two of four post-treatment weeks. Patients were assessed at weeks 13-16 and again approximately six months after treatment.
Response rates favored in-person treatment numerically
Although the primary response rate was 14.7 percentage points lower with smartphone-based therapy than with in-person treatment, the adjusted direct comparison between the two groups was not statistically significant (OR, 1.86; 95% CI, 0.94-3.68; P=.076).
A sensitivity analysis using multiple imputation for missing data also did not establish noninferiority. In that analysis, FDA-defined response rates were 51.4% with smartphone-based hypnotherapy and 56.4% with in-person hypnotherapy, for a difference of –5.0 percentage points (95% CI, –22.7 to 12.8). Although the point estimate was within the prespecified margin, the lower confidence bound remained below –10%.
In-person hypnotherapy was more effective than psychoeducation at weeks 13-16 (OR, 3.48; 95% CI, 1.68-7.20; P<.001).
At six-month follow-up, response rates were 40.3% with in-person hypnotherapy, 33.3% with smartphone-based hypnotherapy, and 14.1% with psychoeducation. Both hypnotherapy groups were more effective than psychoeducation at that point: OR, 4.68 (95% CI, 2.07-10.57; P<.001) for in-person therapy and OR, 3.11 (95% CI, 1.37-7.09; P=.007) for smartphone-based therapy. The difference between the two hypnotherapy groups was not statistically significant at six months (OR, 1.51; 95% CI, 0.75-3.03; P=.253).
Among patients who responded at week 16, sustained response at six months occurred in 70.3% of the in-person group, 64.0% of the smartphone group, and 47.1% of the psychoeducation group.
Secondary outcomes also favored both hypnotherapy approaches over psychoeducation. Using a reduction of at least 50 points on the IBS Symptom Severity Scale, response rates at week 12 were 61.0% with in-person hypnotherapy, 53.3% with smartphone-based hypnotherapy, and 28.2% with psychoeducation. Both hypnotherapy groups also showed significantly greater reductions in IBS Symptom Severity Scale scores over time than the psychoeducation group.
There were no significant between-group treatment effects on psychological symptoms after correction for multiple comparisons.
Access may shape use in practice
Although in-person therapy had the highest primary response rate, the findings suggest smartphone-based delivery could expand access to a therapy otherwise limited by workforce and cost barriers, Dr. Keszthelyi said.
“The key takeaway is that novel modes of hypnotherapy delivery, such as a smartphone-based self-delivered version, can be very helpful in particular in rural areas where the availability of therapists is limited,” he said.
The study authors similarly wrote that smartphone-based self-guided hypnotherapy may represent a viable treatment option for patients with IBS because it can be used regardless of whether a certified therapist is nearby or whether patients can afford therapist-led treatment.
The authors suggested differences in adherence may partly explain the difference in response rates. Self-reported adherence was highest with in-person hypnotherapy, at 85.7% for therapist visits and 72.7% for home exercises, compared with 62.7% for smartphone-based hypnotherapy and 65.4% for psychoeducation.
In the per-protocol analysis, FDA-defined abdominal pain response rates were closer between the hypnotherapy groups: 51.5% with in-person therapy, 48.9% with smartphone-based therapy, and 31.4% with psychoeducation.
The authors noted that a hybrid model, such as one or two face-to-face sessions followed by digital delivery, may warrant further study as a way to improve adherence while maintaining accessibility.
Screening remains important
Dr. Keszthelyi cautioned that smartphone-based access should not mean patients simply download an app and begin hypnotherapy without clinical input.
“Patients should not directly just download a hypnotherapy app and get started,” he said. “A health care professional should first ascertain whether hypnotherapy is indeed the preferred therapy for the individual in question.”
In the trial, patients were screened using questionnaires, particularly with respect to previous trauma, Dr. Keszthelyi said. Patients with elevated anxiety or depression scores were evaluated by an investigator and excluded if anxiety or depression was present because they might be better served by more personalized treatment. The study authors also noted that patients with a history of trauma may relive negative experiences during hypnosis.
“During hypnosis, patients can potentially relive certain traumatic experiences; therefore, these should first be addressed before proceeding with hypnotherapy,” Dr. Keszthelyi said.
Adverse events were reported significantly more often in both hypnotherapy groups than in the psychoeducation group. The most commonly reported events were gastrointestinal symptoms, fatigue, and headache or neck pain. The authors characterized the events as mild, reported that none led to study withdrawal, and said the relatively high number of reports may have reflected daily adverse-event monitoring during treatment.
Missing data among study limitations
The authors noted several limitations. Recruitment was slower than expected, partly because of disruptions during the COVID-19 pandemic, and fewer patients completed treatment than planned. The 18-week run-in, treatment, and post-treatment period may also have contributed to missing daily diary data, and a cyberattack caused an additional period of missing data for some participants.
Missing observations were classified as nonresponse in the primary analysis, which the authors said may have underestimated response rates because responder rates were higher after multiple imputation. They also noted potential selection bias because patients willing to participate in a hypnotherapy trial may have had more favorable attitudes toward the treatment.
The authors said future research should focus on optimizing combinations of in-person and digital hypnotherapy and improving treatment allocation in clinical practice.
The trial was funded by ZonMw, the Netherlands Organisation for Health Research and Development. Dr. Keszthelyi reported research funding from ZonMw, Rome Foundation, Horizon Europe, Horizon 2020, and the Dutch Foundation for Gastroenterology-Hepatology, and a speaker fee from Rome Foundation paid to his host institute. The remaining authors reported nothing to declare.