IBS (Irritable Bowel Syndrome)
Author: Dr Wendy M Gonsalkorale, PhD, Dept of Medicine
University Hospital of South Manchester, UK
ABSTRACT
Objectives: Hypnotherapy has been shown to be effective in the treatment of irritable bowel syndrome in a number of previous research studies. This has led to the establishment of the first Unit in the UK staffed by six therapists which provides this treatment as a clinical service. This study presents an audit on the first 250 unselected patients treated, and these large numbers have also allowed analysis of data in terms of a variety of other factors, such as gender and bowel habit type, that might affect outcome.
Methods: Patients underwent 12 sessions of hypnotherapy over a 3-month period and were required to practise techniques in between sessions. At the beginning and end of the course of treatment, patients completed questionnaires to score bowel and extra-colonic symptoms, quality of life, anxiety and depression, allowing comparisons to be made.
Results: Marked improvement was seen in all symptom measures, quality of life, anxiety and depression (all p<0.001), in keeping with previous studies. All subgroups of patients appeared to do equally well with the notable exception of males with diarrhoea who improved far less than other patients (p<0.001). No factors, such as anxiety and depression or other pre-hypnotherapy variables could explain this lack of improvement.
Conclusions: This study clearly demonstrates that hypnotherapy remains an extremely effective treatment for irritable bowel syndrome which should prove more cost-effective as new, more expensive drugs come on to the market. It may be less useful in males with diarrhoea-predominant bowel habit, a finding that may have pathophysiological implications.
INTRODUCTION
Irritable bowel syndrome (IBS) is a functional bowel disorder, characterised by abdominal pain, distension and altered bowel habit. In addition, patients commonly complain of a variety of extra-colonic symptoms which include nausea, lethargy, backache and urinary symptoms (1) This common condition is estimated to affect 15-20% of the general population at any one time (2) and although only a small proportion (as few as 4% of all IBS sufferers) see a hospital specialist (3), they account for approximately half of the gastroenterologist’s workload (4,5). It is claimed that IBS is much more common in females, since, in the hospital clinic, women outnumber men by as much as 4:1 (2,5) although a recent survey has shown this difference is probably less marked in the general population, being roughly twice as common in women (6). In some cases, symptoms can be so severe and intrusive that they interfere with a person’s quality of life and ability to cope with work, which can result in much time off work (1,6). Such patients are often refractory to current conventional treatment, such that they fail to improve despite a variety of therapeutic interventions (7). It is not uncommon for patients to have undergone repeated investigations and to have been referred to other specialities to seek a cause for their problem, and some may have undergone surgery, such as cholecystectomy and hysterectomy, without symptomatic relief. Patients also tend to consult their own general practitioner for other minor ailments more frequently than other people (8). Thus, for a whole variety of reasons, IBS patients not only continue to suffer from their symptoms but can also be a significant drain on healthcare resources (9).
Hypnotherapy has been shown to be extremely effective in the treatment of IBS, with up to 80% of patients showing improvement in symptoms and overall well-being (10), an effect that is usually sustained (11). A more recent study has demonstrated that hypnotherapy also reduces extra-colonic symptoms, improves quality of life and can help patients return to work (12). In addition, the effectiveness of hypnotherapy has been confirmed by independent studies (13,14).
This work has led to the establishment of the first Hypnotherapy Unit within the National Health Service in the UK devoted to the treatment of patients with IBS, which is currently staffed by a team of six (non-medical) therapists. Since its inception, several hundred patients have already received treatment and this study represents an audit of the first 250 patients treated at this Unit. The large number of patients evaluated in this audit allowed not only classic symptomatology to be assessed but also, unlike in the earlier controlled trials (10, 12, 14), data to be analysed in terms of factors such as age, gender, bowel habit type and psychological status that might affect or predict outcome.
METHODS
Patients
250 patients (aged 19-79 years, 50 male), with IBS of at least two years’ duration and refractory to previous treatment, received a course of hypnotherapy. All patients were on a waiting list for 3 months prior to this and reported that they had had no symptomatic improvement during this time. IBS was defined as the presence of abdominal pain, distension and disturbed bowel habit, together with normal haematology, biochemistry and sigmoidoscopy, in accordance with the Rome I Criteria adopted by the International IBS Working Party (15), with all patients having been previously evaluated by a gastroenterologist. Treatment was offered to patients attending Gastroenterology Clinics at this hospital and other centres in the region whose symptoms continued to be unresponsive to conventional treatment, e.g. laxatives, antidiarrhoeals, antispasmodics or antidepressants, as was deemed appropriate.
Procedure
Patients were seen in consecutive order and treated by the next available therapist. At the first visit, patients completed questionnaires to measure severity of IBS symptoms, associated features and psychological status over the preceding one month. Patients then attended for 12 sessions of hypnotherapy, over a three-month period, usually at weekly intervals, after which they completed questionnaires identical to those before treatment to reflect overall symptom severity after finishing therapy.
Hypnotherapy
Hypnotherapy was carried out based on techniques previously described (10). Briefly, this involved hypnotic induction using progressive relaxation and other procedures to deepen the hypnotic state. This was followed by suggestions, imagery and other techniques appropriate to the individual, such as inducing warmth through the patient’s hands on the abdomen, directed towards control and normalisation of gut function in addition to relevant ego-strengthening interventions. Patients were asked to practise these hypnotic skills on a daily basis with the help of an audio-tape as well as to use them as necessary to relieve symptoms. At each session, interventions were reinforced or modified according to the patient’s needs. After the last session, all patients were asked to contact the Unit at any time for an additional session if they felt they needed further help.
Questionnaires
Questionnaires completed both before and at the end of the course of hypnotherapy included a validated IBS questionnaire (16) rating IBS symptoms, extra-colonic features and quality of life measures, together with the Hospital Anxiety and Depression (HAD) Scale (17).
Analysis of Data
All individual symptoms and quality of life measures were scored in the IBS questionnaire by means of a visual analogue scale (0-100 mm). Increased severity of IBS and extra-colonic symptoms was indicated by a higher score, whereas increased impairment of quality of life measures was denoted by a lower score. Overall scores were calculated as the sum of the following individual items, and this was then adjusted as necessary to give a maximum score as indicated below:
Overall IBS Score (Sum of 5 items; maximum score 500): – pain severity, pain frequency, abdominal bloating, bowel habit dissatisfaction, life interference (extent to which symptoms interfere with life);
Overall Extra-Colonic Score (Sum of 10 items ¸ 2; maximum score 500): – nausea/vomiting, early satiety, headaches, backache, excess wind, heartburn, bodily aches, urinary symptoms, thigh pain, lethargy;
Quality of Life :
– Psychic well-being (coping with problems, confidence, usefulness, security)
– Physical well-being (sleep, energy levels, aches and pains, feeling physically well)
– Mood (irritability, worrying, hopefulness, enjoyment of life)
– Locus of control (feeling in control of life, helplessness, ability to make decisions)
– Social/Relationship (relationships with family/partner, ability to maintain friendships,
feeling of inferiority, feeling wanted, enjoyment of leisure)
– Work (coping with work, satisfaction with work)
The value of each quality of life measure was derived from the mean of the individual items shown indicated in parentheses, to give a maximum score of 100.
Calculation of improvement in scores after hypnotherapy
Improvement in scores after hypnotherapy was calculated as the percentage (%) change in score as follows:
(Pre-hypnotherapy score – post-hypnotherapy score) x 100
pre-hypnotherapy score
with positive values representing improvement and negative values representing deterioration of symptoms.
Improvement in bowel habit
Patients also rated bowel habit in the IBS questionnaire in terms of stool frequency (maximum and minimum number of bowel movements/day), stool consistency (occurrence as ‘often’, ‘occasionally’ or ‘never’ of stools as ‘normal’, ‘hard’, ‘pellety’, ‘stringy’, ‘mushy’, ‘watery’) and other measures (the presence or absence of: mucus, blood, urgency, straining, rectal dissatisfaction). Overall change in bowel habit was assessed by comparing pre- and post-hypnotherapy scores for the above measures independently of the other questionnaire scores. An integer score of 0, 1, 2 or 3 was given to denote the degree of change in bowel habit after hypnotherapy (where 1= slight, 2 = moderate, 3 = marked, and each assigned with either a negative (-) value, for deterioration, or a positive (+) value for improvement, and zero representing no overall change).
Statistical Analysis
Many individual symptom scores followed a non-normal distribution and a suitable ‘normalising’ transformation could not be found. Hence, median values (with interquartile range, IQR) were used for symptom scores, and mean values (with 95% confidence intervals, CI) for HAD (anxiety and depression) scores. Intraindividual pre- and post-hypnotherapy scores were compared using the Wilcoxon Pairs test, the paired t-test or McNemar’s test, as appropriate. Comparison between independent groups was carried out using the Mann Whitney ‘U’ test, t-test, or Chi-square test (two groups) together with the Kruskal-Wallis test or analysis of variance (more than two groups). Spearman (r) correlation coefficients were calculated to assess relationships between variables. For the purposes of further analysis, patients were also subdivided according to gender and bowel-habit type, based on Rome criteria I. Multiple regression was performed on pre-hypnotherapy measures to identify any factors affecting improvement in symptom scores.
Overall scores for IBS and extra-colonic features and quality of life measures, were treated as the primary outcomes, and therefore no adjustment was made for multiple comparisons. However, for the purpose of comparing secondary endpoints (i.e. individual measures making up overall scores), only differences at the 0.1% level (p<0.001) were interpreted as showing reasonable evidence of a true difference because of the large number of multiple comparisons made.
RESULTS
232 of the 250 patients in this series completed the full course of 12 sessions of hypnotherapy. The remaining 18 discontinued before this (having from 8 to 10 sessions) because they had achieved marked improvement and felt confident that they no longer needed to attend. These patients completed the post-hypnotherapy questionnaires within two weeks of their last session and the data treated as if this was after 12 sessions. No patients discontinued before completing 12 sessions for other reasons.
IBS Symptomatology and Extra-Colonic Features
Following hypnotherapy, improvement was seen in the overall IBS score (p<0.001) and in all individual features measured, namely pain severity, pain frequency, bloating, bowel habit dissatisfaction and life interference (all p<0.001; Figure 1).
Improvement in bowel habit scores, based on data for stool frequency and consistency from pre- and post-hypnotherapy questionnaires, revealed that 78% of patients had improved bowel habit after hypnotherapy (bowel habit scores ³1), while approximately 13% had no overall change and 9% suffered slight deterioration. Furthermore, there was a direct correlation between this in bowel habit score and change in patients’ reported dissatisfaction with bowel habit (r=0.537; p<0.001).
The prevalence of individual extra-colonic features varied, with those of lethargy, bodily aches, backache, urinary urgency and excess wind being the most common and severe. However, all individual extra-colonic symptoms, as well as the overall extra-colonic score, improved significantly after hypnotherapy (all p<0.001; Figure 2).
Quality of Life, Anxiety and Depression
Hypnotherapy significantly improved all measures of quality of life (all p<0.001), as shown in Figure 3. There was also a reduction in both anxiety [HAD ‘A’ (anxiety) score pre- v post-hypnotherapy (HT), mean (95% CI): 11.1(10.5-11.6) v 7.4(6.9-7.9), p<0.001] and depression [HAD ‘D’ (depression) score: 7.2(6.7-7.7) v 4.1(3.6-4.5), p<0.001]. Moreover, after treatment, fewer patients were classified as clinically anxious (HAD ‘A’ score >9, pre-HT v post-HT: 69.3% v 34.3%, p<0.001) or depressed (HAD ‘D’ score >9: 36.1% v 14.6%, p<0.001).
In addition, improvement (% change) in overall IBS score directly correlated with improvement (% change) in i) overall quality of life score (r=0.577, p<0.001), ii) anxiety (r=0.526, p<0.001) and iii) depression (r=0.530, p<0.001).
Analysis with respect to age
There was only a weak association between improvement in IBS symptoms and age, as shown by the very low negative correlation coefficient (r= -0.132, p=0.038). This would indicate that age could account for less than 2% of the variance in symptomatic improvement.
Analysis with respect to gender and bowel habit type
Patients were subdivided according to gender and bowel habit type based on the Rome I Criteria to allow further comparisons to be made. The overall ratio of females to males was 4:1 (200 females, 50 males) with no difference in age range between the two sexes [mean (95%CI): males (M) v females (F), F: 45.1(41.1,49.1) v 44.5(42.5,46.5), p=0.802]. Proportionately more males had diarrhoea-predominant bowel habit and fewer were in the constipation-predominant group, compared with females (M v F: diarrhoea-predominant: 44% v 26%, constipation-predominant: 16% v 26%, alternating: 40% v 48%, p=0.02).
Pre-Hypnotherapy Scores
It can be seen from Table 1 that prior to hypnotherapy, females generally had a higher overall IBS score than males [M v F, median: 300 v 343, p<0.005] and, in terms of the individual components of this score, they complained of more severe bloating (p<0.001). Inspection of data from the different bowel habit types revealed that in the diarrhoea-predominant group males had less severe pain than the females (p<0.001). In addition, patients with diarrhoea (males and females, collectively) were significantly more dissatisfied with their bowel habit than patients with other bowel habit types [diarrhoea v constipation v alternating, median(IQR): 90(67,100) v 67(55,96) v 67(48,94), p<0.001].
Females as a whole had more severe extra-colonic symptoms than males, as shown by the higher overall score [M v F, median: 191 v 236, p<0.001]. In particular, they had significantly more thigh pain and bodily aches (both p<0.001), differences which were most evident in the constipation and alternating bowel habit groups. Females also tended to complain of more nausea (p<0.005).
With regard to levels of anxiety and depression, males with constipation and alternating bowel habit, but not those with diarrhoea, were less anxious than females [HAD ‘A’ scores, mean (95%CI): constipation: M: 7.8(5.7,9.8), F: 11.7(10.4, 13.0); alternating: M: 9.3(7.2, 11.4), F: 11.7(10.8,12.6); diarrhoea: M: 11.6(9.4,13.8), F: 10.5(9.2,11.8), sex/bowel habit interaction p=0.02].
Post-hypnotherapy Scores
Scores for individual IBS symptoms, overall IBS and extra-colonic scores are shown in Table 2. Although the overall IBS score was higher in females than males before hypnotherapy, it was lower in females by the end of treatment [M v F: median 178 v 151, p<0.05) and this was reflected in greater overall improvement (% change) in this score, being 52% in females compared with 33% for males (p<0.001). However, this difference in response was determined by the fact that males with diarrhoea in particular did less well, having a higher overall IBS score after therapy and showing less improvement than either females with diarrhoea [M v F: overall IBS score, median: 229 v 159, p<0.001; improvement in IBS score (% change): 20% v 53%, p<0.001] or patients in the other bowel habit groups (p<0.001). This higher IBS score in males with diarrhoea was due largely to ratings for interference with life and possibly bowel habit dissatisfaction remaining higher than patients in other groups (p=0.002). Indeed, stool frequency remained greater for these patients than for females with diarrhoea [M v F: maximum/week: 28(14,42) v 21(14,28), p<0.01], and correlated with bowel habit dissatisfaction and life interference (r=0.644 and r=0.389, respectively, both p<0.001). Furthermore, improvement in actual bowel habit was also significantly lower in males with diarrhoea, with only 54% of these patients, compared with 82% of females with diarrhoea, having improved bowel habit (Bowel habit improvement rating, M with diarrhoea v F with diarrhoea (% of patients): marked improvement (bowel habit score +3): 4% v 4%; moderate improvement (+2): 9% v 32%; slight improvement (+1): 41% v 46%; no overall change (0): 27% v 8%; slight deterioration (-1): 18% v 0%, p<0.001). This measure also correlated directly with improvement in bowel habit dissatisfaction and life interference (r=0.667 and r=0.748, respectively; both p<0.001).
Improvement in the overall extra-colonic score was also significantly less in males with diarrhoea, compared with females in the same group [improvement (% change), median : M v F: 16% v 42%, p<0.001) and other bowel habit types (p<0.001). There was a trend towards the individual symptoms of lethargy, excess wind and heartburn remaining higher in these male patients compared with females with diarrhoea [M v F: Lethargy, median(IQR): 63(35,75) v 27(21,73), p=0.034; Excess wind: 56(40,75) v 25(13,65), p=0.005; Heartburn: 21(5,40) v 6(1,25), p=0.008] and males in the other bowel habit groups (all p<0.05). In addition, males with diarrhoea retained higher scores for depression than the other groups [HAD ‘D’ score, mean (95% CI): constipation: M: 3.1(0.0,7.3), F: 3.7(2.8,4.7); alternating: M: 4.4(2.9,5.8), F: 4.0(3.3,4.8); diarrhoea: M: 6.8(5.2,8.4), F: 4.0(3.3,4.8), sex/bowel habit interaction p=0.011].
Further analysis was undertaken to identify any possible factors or variables measured prior to hypnotherapy that might explain or be associated with poor outcome in males with diarrhoea. Multiple regression analysis confirmed that males with diarrhoea had a significantly lower improvement score compared with other bowel habit categories and females as a whole (p=0.001). However, this lack of improvement could not be explained by any factors, such as anxiety or depression, included as other predictor variables in the regression analysis. In female patients only, improvement in symptoms was found to be directly related to pre-hypnotherapy levels of bowel habit dissatisfaction (p=0.020) and inversely related to depression (p=0.021).
Discussion
This audit is the first large scale review of hypnotherapy in IBS which not only confirms earlier findings that it is an effective treatment for this condition (10-14) but adds some important new observations. The most interesting finding in this respect was that males with diarrhoea-predominant bowel habit did far less well with hypnotherapy than the other patient groups.
In the patients as a whole group, IBS symptoms of abdominal pain, bloating and bowel habit disturbance, together with all extra-colonic symptoms, were significantly reduced after hypnotherapy and were considered to interfere with life far less than before. The subjective rating of bowel habit dissatisfaction used in the symptom questionnaire to assess bowel habit disturbance proved to be a simple yet reasonably accurate measure, since changes in dissatisfaction after treatment directly correlated with actual changes in bowel habit. In addition, patients’ quality of life improved and ratings for anxiety and depression were lower, with fewer patients remaining significantly anxious or depressed after treatment. Furthermore, the improvement seen in IBS symptomatology was related to improvement both in quality of life and psychopathology (anxiety and depression). It is reasonable to conclude that this association indicates that improvement in patients’ quality of life and psychological well-being occurred as a consequence of reducing symptoms. However, one cannot rule out that hypnotherapy could have had at least some partial effect by directly reducing anxiety and depression. This in itself could also help to improve symptomatology, particularly if psychological factors played a role in triggering or exacerbating symptoms.
The possibility that the results of this audit are influenced at least in some way by expectations that patients had about the outcome of treatment cannot be entirely ruled out. However, less than 10 patients had actively sought out hypnotherapy treatment, and it is of interest that in our own Gastroenterology Clinic it is estimated that less than 2% turn down hypnotherapy when it is offered. Thus, selection bias should not be a major problem associated with this report.
The results in this study represent an audit of patients undergoing hypnotherapy as part of the clinical service now offered routinely on the basis of favourable outcome in previous research studies. Since this was not a clinical trial, no control group was included here for comparison, but previous studies that have included control groups have demonstrated that hypnotherapy was superior to placebo or non-treatment (10,12,14). In addition, all patients in the present study had waited at least 3 months for treatment, and patients reported that no improvement in symptoms occurred during this time. The outcome of therapy was measured soon after the last therapy session and no longer term follow-up has systematically been pursued at this stage since obtaining data on such a large scale would present difficulties. However, it has been shown previously that improvement in symptoms with hypnotherapy is largely sustained (11,12,14), although some patients may require occasional ‘top-up’ sessions to maintain improvement (11).
The possible effect of age on response to therapy was assessed since it had been observed in an earlier study that patients over 50 years of age improved less than younger patients (11). In this present study, however, the association between age and degree of symptomatic improvement was found to be very weak and reached statistical significance only because of the very large numbers of patients involved. Therefore, it seems reasonable to conclude that age is not a significant factor affecting outcome and that older patients could generally be expected to benefit as much as younger patients.
There were fewer male patients than females, but the ratio of males to females was 1:4, which is in keeping with the pattern seen in most hospital out-patient departments (2,5). Although the numbers in some subsets were small, particularly the constipated males, it was considered that they were sufficient for further analysis. Analysis of pre-hypnotherapy measures revealed some differences in the pattern of symptoms between the various patient groups. Females, particularly those with constipation and alternating bowel habit, complained of more bloating and had more extra-colonic symptoms than males. An earlier study reported a greater incidence of these symptoms in constipated patients compared with patients with diarrhoea, but with no apparent effect of gender (18). In the diarrhoea-predominant group, males had less severe pain than females, and both males and females in this group were more dissatisfied with their bowel habit than other patients. Males, except for those with diarrhoea, were also less anxious than females.
Males with diarrhoea, as a group, improved far less than other patient groups with hypnotherapy, as evidenced by a much smaller degree of change in the overall IBS score. This was largely determined by the fact that ratings for bowel habit dissatisfaction and life interference remained higher after treatment, and these in turn were associated with greater continued disturbance in bowel habit, as measured by stool frequency and consistency. In addition, males with diarrhoea retained more extra-colonic symptoms and a higher score for depression than other patients after treatment. The failure of males with diarrhoea to respond as well to treatment was not obviously connected with any of the variables measured before hypnotherapy. Although males with diarrhoea were more anxious than other males, their levels of anxiety were similar to females, and no association was found between pre-hypnotherapy scores of anxiety and symptomatic improvement. Depression was found to be a significant factor in outcome only for females but not males. Furthermore, improvement of IBS symptoms was not associated with any of the other pre-hypnotherapy measures. In seeking other explanations for this lack of improvement, one possibility is that males generally have somewhat lower hypnotic or imaginative abilities than females, so that they would be not as well suited to a hypnotherapeutic approach. Alternatively, males may have been less amenable to this intervention because it was delivered by a female therapist. However, if either explanation is true, one would have expected males in the other bowel habit groups also to have done less well, which is clearly not the case.
Hypnotic ability was not measured in patients in this study using formal hypnotic susceptibility testing since it is time-consuming and is generally regarded as not being necessarily predictive of how well patients respond in the clinical setting (19). However, hypnotic susceptibility testing was conducted in a recent controlled trial of hypnotherapy in IBS patients (14) and no association was found between hypnotic ability and response to treatment.
Another possibility to be considered is whether males with diarrhoea do in fact represent a somewhat different group of patients with regard to the pathophysiological mechanisms underlying symptoms, which may be less amenable to modification using hypnotherapy. A differential response was also observed in preliminary clinical trials with a 5-HT3 antagonist for use in non-constipated patients which showed that females responded significantly better than males (20,21). These findings suggest that there might be pathophysiological differences between males and females with diarrhoea and therefore one might speculate that, in some way, this could be the reason for the reduced responsiveness of males with diarrhoea to hypnotherapy.
In conclusion, this study clearly demonstrates that hypnotherapy remains an extremely effective treatment for IBS, even in the more challenging environment of a general service from which no referral is excluded from treatment. One new observation emerging from the data is that hypnotherapy may be less useful in males with diarrhoea-predominant bowel habit, a finding that warrants further study. Lastly, new, more expensive drugs are likely to come on to the market in the near future. However, it has been shown that their beneficial effect is lost shortly after cessation of treatment (22,23) which is in sharp contrast to hypnotherapy where the symptomatic improvement is longlasting. Thus, hypnotherapy will also become a much more cost-effective option in the treatment of irritable bowel syndrome.
Acknowledgements
We thank the other Hypnotherapy Unit staff who treated some of the patients used in this study: Mrs P. Cooper, Mrs P. Cruickshanks, Mrs V Miller, Mrs J Randles and Mrs V Whelan. We also thank Mrs Julie Morris, Head of Medical Statistics, University Hospital of South Manchester, for help with statistical analysis.
Conflicts of interest – none
REFERENCES
1 Whorwell PJ, McCallum M, Creed FH, et al. Non-colonic features of irritable bowel syndrome. Gut 1986;27:37-40.
2 Thompson WG. Irritable bowel syndrome: prevalence, prognosis and consequences. Canadian Medical Association Journal 1986;134:111-3.
3 Thompson WG, Heaton KW, Smyth T, et al. Irritable bowel syndrome: the view from general practice. Eur J Gastroenterol Hepatol 1997;9:689-92.
4 Switz DM. What the gastroenterolgoist does all day. A survey of a state society’s practice. Gastroenterology 1976;70:1048-50.
5 Harvey RF, Salih SY, Read AE. Organic and functional disorders in 2000 gastroenterology outpatients. Lancet 1983;i:632-4.
6 Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders: prevalence, sociodemography and health impact. Dig Dis Sci 1993;38:1569-80.
7 Holmes KM, Salter RH. Irritable bowel syndrome – a safe diagnosis. Br Med J 1982; 285:1533-4.
8 Maxton DG, Whorwell PJ. Use of medical resources and attitudes to health care of patients with ‘chronic abdominal pain’. Br J Med Econ 1992;2:75-9.
9 Talley NJ, Gabriel SE, Harmsen WS, et al. Medical costs in community subjects with irritable bowel syndrome. Gastroenterology 1995;109:1736-41.
10 Whorwell PJ, Prior A, Faragher EB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable bowel syndrome. Lancet 1984;ii:1232-4.
11 Whorwell PJ, Prior A, Colgan SM. Hypnotherapy in severe irritable bowel syndrome: further experience. Gut 1987;28:423-5.
12 Houghton LA, Heyman DJ, Whorwell PJ. Symptomatology, quality of life and economic features of irritable bowel syndrome – the effect of hypnotherapy. Aliment Pharmacol Ther 1996;10:91-5.
13 Harvey R, Hinton RA, Gunary RM, et al. Individual and group hypnotherapy in the treatment of refractory irritable bowel syndrome. Lancet 1989;i:424-5.
14 Galovski TE, Blanchard EB. The treatment of irritable bowel syndrome with hypnotherapy. Appl Psychophysiol Biofeedback 1998;23:219-32.
15 Thompson WG, Creed F, Drossman DA, et al. Functional bowel disorders and functional abdominal pain. Gastroenterol Int 1992;5:75-91.
16 Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997;11:395-402.
17 Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67:361-70.
18 Schmulson M, Lee OY, Chang L, et al. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol 1999;94:2929-35.
19 Yapko M. Trancework: an introduction to the practice of clinical hypnosis, 2nd ed. 1990. New York: Brunner/Mazel, 1990.
20 Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999;13:1149-59.
21 Bardhan KD, Bodemar G, Geldof H, et al. A double-blind, randomised placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2000;14:23-4.
22 Jones RH, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999;13:1419-27.
23 Camilleri M, Northcutt AR, Kong S, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000;355:1035-40.