Six vs 12 Sessions of Gut-focused Hypnotherapy for Irritable Bowel Syndrome: A Randomized Trial

Abstract

Gut-focused hypnotherapy has been shown to be a highly effective treatment for irritable bowel syndrome (IBS) in randomized controlled trials.1Black C.J. et al.Gut. 2020; 69: 1441-1451Crossref PubMed Scopus (36) Google Scholar Previous studies have not only demonstrated long-term efficacy on IBS symptoms, but have also demonstrated improvement in noncolonic symptoms, anxiety, quality of life, and reduced healthcare utilization.2Gonsalkorale W.M. et al.Gut. 2003; 52: 1623-1629Crossref PubMed Scopus (204) Google Scholar, 3Houghton L.A. et al.Aliment Pharmacol Ther. 1996; 10: 91-95Crossref PubMed Google Scholar, 4Miller V. et al.Aliment Pharmacol Ther. 2015; 41: 844-855Crossref PubMed Scopus (59) Google Scholar, 5Vasant D.H. et al.Frontline Gastroenterol. 2020; (Epub ahead of print. https://doi.org/10.1136/flgastro-2020-101679)PubMed Google Scholar Recently, it has been suggested that the number of treatment sessions might be an important predictive factor for outcomes.6Krouwel M. et al.Complement Ther Med. 2021; 57: 102672Crossref PubMed Scopus (2) Google Scholar However, this has not been previously studied, and therefore no consensus is available on the optimal volume of sessions. The purpose of this study was to determine if outcomes from an abbreviated course of 6 sessions of gut-focused hypnotherapy were noninferior to those achieved after 12 sessions. In a randomized controlled, noninferiority, single-blind trial with a parallel design, all patients referred to the hypnotherapy unit were screened for eligibility, which required fulfillment of the Rome III diagnostic criteria for IBS and National Institute for Clinical Excellence recommended criteria for gut-focused hypnotherapy.7National Institute for Healthcare and Excellence guidelines. 2008; : CG61Google Scholar Exclusion criteria are detailed in the Supplementary Methods. Patients were allocated to either 6 or 12 weekly sessions using a computer-generated randomization sequence. After an introductory consultation with the hypnotherapist, patients in both groups received gut-focused hypnotherapy using the Manchester protocol.8Vasant D.H. et al.Neurogastroenterol Motil. 2019; 31e13573Crossref PubMed Scopus (17) Google Scholar Apart from the number of sessions, the 2 sessions were similar. Outcomes were assessed using a series of validated questionnaires completed at baseline and at the end of treatment (at 6 weeks for the 6-session group and at 12 weeks for the 12-session group). These questionnaires, described in Supplementary Methods, included the IBS Symptom Severity Score (IBS-SSS), noncolonic symptom score, quality-of-life score, Hospital Anxiety Depression (HAD), and the EQ-5D. The primary outcome was a ≥50-point reduction in the IBS-SSS. The percentage of patients experiencing a ≥30% reduction in the pain severity subscores of the IBS-SSS was also calculated. To allow for up to a 25% dropout, 450 subjects were required overall to ensure 360 subjects completed the study (180 per group), with an 80% power to detect a noninferiority margin of a 12% difference between the groups. Data were analyzed using a modified intention-to-treat approach. Multiple imputations using the iterative Markov chain Monte Carlo procedure were used for all missing outcomes data. Analysis of covariance or multiple logistic regression analysis was used to compare outcomes between groups after adjustments for baseline anxiety, depression, and EQ-5D scores; age; sex; and IBS subtype. The noninferiority margin was assessed by examination of the lower limit of the 1-sided 95% confidence intervals (CIs). The consort flow diagram (Supplementary Figure 1) summarizes recruitment and patient flow throughout the study. Overall, of 448 patients who were included in the modified intention-to-treat analyses, 226 were allocated to 6 sessions and 222 to 12 sessions of hypnotherapy. Baseline characteristics, including patient demographics, IBS severity, noncolonic symptom scores, quality of life scores, HAD, and EQ-5D scores were similar in the 2 randomized groups (Supplementary Table 1). In the modified intention-to-treat analysis, a ≥50 point reduction in IBS-SSS was achieved by 178 of 226 patients (78.8%) after 6 sessions and by 164 of 222 patients (73.9%) after 12 sessions, with evidence of noninferiority (adjusted logistic regression analysis: mean difference, 5.1%; 95% CI, –3% to 13%). Similarly, adjusted logistic regression analysis confirmed noninferiority in the proportion achieving a ≥30% reduction in abdominal pain score (mean difference, 6.3%; 95% CI, –4% to 16%) (Figure 1). Other mean differences in secondary outcomes after 6 and 12 sessions were also similar when compared using adjusted logistic regression analyses (noncolonic symptom score, –7.2 [95% CI, –20.9 to 6.5]; improvement in quality of life scores, 8.9 [95% CI, –3.4 to 21.2]; EQ-5D health state scores, 0.02 [95% CI, –0.021 to 0.064], and HAD-depression, –0.5 [95% CI, –1.1 to 0.1]). However, the mean difference in improvement in EQ-5D visual analog scale and HAD-anxiety were greater after 6 compared with 12 sessions (EQ-5D visual analog scale, 3.3 [95% CI, 0.2–6.4; P =.037]; HAD-anxiety, 0.8 [95% CI, –1.5 to –0.2; P = .01]). Of 448 patients, 54 (12%) dropped out of the study, with a greater percentage of dropouts from the 12-session group compared with the 6-session group (34 [15%] vs 20 [9%], respectively; P = .042). This study, which is the largest randomized study of gut-focused hypnotherapy to date, suggests that an abbreviated course is at least as effective as our standard approach. Compared with 12 sessions, 6 sessions of hypnotherapy led to similar levels of improvement in IBS symptoms, noncolonic symptoms, anxiety, depression, and quality of life, which were almost identical to outcomes previously reported from our unit.4Miller V. et al.Aliment Pharmacol Ther. 2015; 41: 844-855Crossref PubMed Scopus (59) Google Scholar There was a trend for the 6-session regimen to perform slightly better on all endpoints measured, and this reached significance for EQ-5D visual analog scale and anxiety. Importantly, the dropout rate after 6 sessions was lower than after 12 sessions, further strengthening the case for this approach. Several factors might explain these results. There is less time pressure associated with the 12-session approach, allowing therapists to take their time with treatment. Similarly, for the patient, the end may seem a long way off, and therefore engagement with treatment may not be as strong. Consequently, the abbreviated treatment could plausibly lead to stronger motivation by both patient and therapist. Furthermore, momentum may be an important factor, and the abbreviated regimen allows less time for interruption by unforeseen circumstances such as sickness or holidays. Limitations of this study include the lack of long-term follow-up data to determine the durability of the effects of the abbreviated hypnotherapy regimen. This could be investigated in future studies. Also, although unlikely, we cannot eliminate the risk of selection bias influencing the dropout rates observed, because some participants may have had preconceptions that 1 of the 2 options might be more effective for them. Nonetheless, these data suggesting that 6 sessions of hypnotherapy for IBS are at least as effective as 12 have important clinical implications. Six as opposed to 12 sessions could halve the cost of hypnotherapy, double the output of an individual hypnotherapist and unit, and may improve access to this effective form of treatment by making it more attractive to purchasers. The authors acknowledge Mrs Valerie Boswell, who helped with recruitment and trial administration; Mrs Pamela Cruickshanks, Mrs Irene Rooney, Mrs Victoria Whelan, and Mr William Fowler, who treated patients randomized into the conventional group; and Dr Helen Carruthers, PhD, medical illustrations manager at Wythenshawe Hospital, who helped optimize the figures in the manuscript. Syed S. Hasan, PhD (Data curation: Lead; Investigation: Equal; Methodology: Equal; Writing – review & editing: Supporting). Peter J. Whorwell, MD (Conceptualization: Lead; Funding acquisition: Lead; Methodology: Equal; Resources: Lead; Writing – review & editing: Equal). Julie Morris, MSc (Formal analysis: Lead; Methodology: Equal; Writing – review & editing: Supporting). Dipesh H. Vasant, MBChB, PhD, MRCP (Formal analysis: Equal; Writing – original draft: Lead; Writing – review & editing: Lead). Vivien Miller (Investigation: supporting, Writing –review & editing: supporting, methodology: supporting). Exclusion criteria were those with any other significant medical condition affecting their overall health, patients suffering from any other gastrointestinal disease, and patients on antipsychotic medication. However, those on antidepressants were included, providing they remained on a stable dose throughout the trial. The following outcome questionnaires were collected by an independent member of the department who was blinded to the treatment allocation of the patients. The severity of IBS symptoms was assessed using IBS-SSS.1Francis C.Y. et al.Aliment Pharmacol Ther. 1997; 11: 395-402Crossref PubMed Google Scholar This score, comprising 5 components (pain severity, pain frequency, abdominal bloating, bowel habit dissatisfaction, and life interference) was used as the primary outcome measure and to assess some secondary outcomes. Each component scores up to a maximum of 100. To assess the percentage response to hypnotherapy, the proportion of patients achieving a 50-point or more reduction in symptom severity was calculated, because it has been previously shown that a 50-point reduction or more represents a clinically significant improvement.1Francis C.Y. et al.Aliment Pharmacol Ther. 1997; 11: 395-402Crossref PubMed Google Scholar Response rates for the more demanding endpoints of a reduction in score of 100 and 150 points were also calculated. The secondary outcome measure for pain was the proportion of patients achieving a ≥30% reduction in pain scores as specified by the US Food and Drug Administration as an indicator of response to treatment.2US FDAFederal Register; Vol. 77,No.105 pp:32124-32125.2012Google Scholar Consequently, to comply with this US Food and Drug Administration recommendation, the percentage of patients experiencing a reduction of 30% or more in their pain score was calculated from the pain components of the IBS-SSS.3Gonsalkorale W.M. et al.Am J Gastroenterol. 2002; 97: 954-961Crossref PubMed Google Scholar Noncolonic symptoms are highly intrusive and debilitating for patients. Improvement in these symptoms is considered to be an important outcome of therapy.3Gonsalkorale W.M. et al.Am J Gastroenterol. 2002; 97: 954-961Crossref PubMed Google Scholar The noncolonic score consists of 10 items (nausea/vomiting, early satiety, headaches, backache, lethargy, excess flatulence, heartburn, urinary symptoms, thigh pain, and pains in muscles and joints), which each provide a score out of 100, the sum of which is divided by 2 to give a maximum score out of 500. This consists of 15 items (coping with problems, confidence and security, quality of sleep, feelings of irritability, frequency of worrying, enjoyment of life, feelings of hopefulness, physical well-being, relationships with others, maintaining friendships, feelings of inferiority, feeling wanted, feelings of helplessness, difficulty making decisions, and enjoyment of leisure time), which are scored on a 0–100 scale with higher scores indicating a better quality of life.3Gonsalkorale W.M. et al.Am J Gastroenterol. 2002; 97: 954-961Crossref PubMed Google Scholar The sum of these 15 components is divided by 3 to give a maximum quality of life score out of 500. The HAD scale is a validated instrument used to assess both anxiety and depression. This HAD scale provides an anxiety score out of a maximum of 21 points and, similarly, a depression score with a maximum score of 21.4Miller V. et al.Aliment Pharmacol Ther. 2015; 41: 844-855Crossref PubMed Scopus (59) Google Scholar,5Vasant D.H. et al.Frontline Gastroenterol. 2020; (Epub ahead of print. https://doi.org/10.1136/flgastro-2020-101679)PubMed Google Scholar A HAD score of ≥10 for either domain was used as an indicator of either clinically significant anxiety or depression for the purposes of this study. The EQ-5D questionnaire, an instrument comprising 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) provides a score calculated in such a way that a score of 1 equals full health. In addition, it also includes a visual analog scale to record a self-rated health state from worst imaginable to best imaginable.6EuroQol Research Foundation. EQ-5D-5L user guide; 2019. Available at: https://euroqol.org/publications/user-guides. Accessed April 10, 2021.Google Scholar The study was approved by a Research Ethics Committee (REC, 07/Q1403/108; trial registration number, ISRCTN61738583) and was conducted between October 2009 and August 2014. All authors had access to the study data and reviewed and approved the final manuscript. Values are n (%) unless otherwise defined. SD, standard deviation.

Topics & Concepts