Cognitive-behavioural therapy has no effect on disease activity but improves quality of life in subgroups of patients with inflammatory bowel disease: a pilot randomised controlled trial

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal (GI) tract, with a rising incidence worldwide. IBD’s aetiology is thought to involve a deregulated immune response to intestinal microbiome, triggered by environmental factors, in those with a genetic susceptibility. In addition, a psycho-neuro-immunological view of IBD has developed in recent years due to intriguing observations that psychological status can directly influence inflammatory lesions in the gut [1]. Although IBD has not, to date, been confirmed to be causally linked to psychological factors, psychological stress has been reported to be one of the strongest predictors of symptomatic disease course [2,3] and also linked to increased inflammation [4]. A review by Graff et al. has demonstrated that depression negatively influences IBD course [5]. However, it needs to be acknowledged that in the majority of the available studies, reported symptoms rather than actual inflammation (measured e.g. using fecal calprotectin or histology scores) are the outcome measure and thus it remains unclear how much of this relationship is explained by symptom perception versus inflammatory activity. Further to this, although the research on stress, depression and inflammation in animals has provided more than convincing evidence of their inter-relationships in IBD, replicating these observations in humans is challenging for ethical reasons. Hence, the question of this relationship needs to be addressed indirectly by testing whether delivering a therapy known to enhance psychological wellbeing (i.e. psychotherapy) may protect against IBD-related inflammation and prevent flares.

Given the observed relationship between stress, depression and IBD disease course and also the encouraging data on the treatment of functional gut disorders with psychotherapy [6], interest in the possible efficacy of psychological interventions in IBD has been growing. In recent years, several reviews have been published on the efficacy of psychotherapy for QoL, emotional status and remission/flare status in IBD [7-10]. A Cochrane meta-analysis of randomized controlled trials found no evidence for the efficacy of psychotherapy in improving QoL, emotional status or proportion of patients not in remission in the short term or at 12 months in unselected adults with IBD, although it suggested that psychotherapy may result in benefits for subgroups of patients [8]. However, here, ideologically dissimilar psychological interventions were grouped together possibly clouding the conclusions. One of the recent reviews [9] has addressed this weakness of the previous review and concluded that cognitive-behavioural therapy (CBT) - a psychotherapy where people are taught to identify and modify unhelpful thinking styles and maladaptive behaviours - is associated with improvement in distress, although it has resulted in benefits with respect to IBD symptoms only in some reports.

Thus, the present trial aimed to investigate whether CBT in addition to standard medical therapy prolongs remission in IBD in comparison with standard therapy alone. As IBD is a life-long condition [11] and there is the potential for a bidirectional interaction between psychological status and disease relapse [12], and the additional factor that life stresses and psychological status are not constant over time, we chose to examine the effect of CBT in a general cohort of IBD patients in remission rather than only those with current depression and/or anxiety. Given the primary outcome measure and the main focus of the trial was on disease activity over time rather than treating anxiety or depression, this was considered the most optimal approach.

It was hypothesised that the benefits of adding CBT would be two-fold:

Patient recruitment is presented in Figure 1. Overall, 174 patients participated in the study: 90 in the +CBT group and 84 in SC.

This trial is the largest to date to explore the potential usefulness of CBT in managing disease activity and mental health in IBD. A pragmatic approach to its delivery was chosen, offering participants a choice between face-to-face and online CBT, designed to mirror each other.

The most important finding of the study is that adding CBT to standard care was not found protective of IBD remission over a period of 12 months. Further to this observation, participants who received CBT were not found to differ in their scores on anxiety, depression and coping measures at 6 months when controlling for baseline, a finding in contrast to previous small studies [36-40] and unusual given the high efficacy of CBT in treating anxiety and depression [41]. It can perhaps be explained by low anxiety and depression scores at baseline, and thus since the mental health of these participants was generally good at the outset, there was little that could be gained from the intervention. A subgroup analysis of participants ‘in need’ (with high scores on mental health subscales), showed that CBT was effective in improving this group’s QoL at 6 months, thus confirming that CBT works in those who need it. At 12 months, due to attrition, the comparison was underpowered and thus future studies should establish long-term effect of CBT on QoL in the subgroups of IBD classified as ‘in need’. A study using psychodynamic therapy for a similar unselected sample also showed no relationship between psychotherapy and disease activity in IBD, although unlike in our study, theirs showed trends towards improved disease activity and fewer surgical interventions [42]. On the other hand Keefer et al. [43] showed that gut-directed hypnotherapy prolongs clinical remission in IBD. Though Keefer et al.’s study [43] had a small sample size, their promising results may indicate that hypnotherapy rather than therapies such as CBT or psychodynamic may play a role in maintenance of IBD remission.

Regarding the participants ‘in need’, this group was identified based on the recommendations from previous papers [8,44]. Indeed, looking at this subgroup separately, we showed that CBT does improve mental QoL at least at short-term. Curiously, no improvements in anxiety or depression were observed in the group ‘in need’, however, given its size (34 CBT and 40 controls), it is possible that if the sample had been larger these improvements would have appeared and possibly a longer observation period could also verify this finding. Future studies should focus on targeting psychotherapeutic interventions at the group ‘in need’ rather than the general IBD population and should confirm these results on a larger sample to allow for significant attrition.

Interestingly, this trial did not show F2F to be significantly different to cCBT in efficacy, with the exception of one dimension of coping (showing F2F group to fare better at 12 months), although, admittedly the trial was not powered for this subgroup analysis. Participants nearly always preferred the online CBT delivery as it fitted with their life style and commitments and thus it is reassuring that the efficacy of the modalities was similar. This mode of delivery also allowed for recruiting participants who usually do not take part in trials as they live in remote areas, increasing the generalisibility of our data. However, the attrition in the online CBT group was significantly larger than in the F2F group and the ways to address high attrition should be examined in future studies. Alternatively larger samples could be utilised.

Further, and interestingly, we observed no marked relationship between the amount of CBT used and the outcomes. Only when we compared users to non-users (in the CBT group but not using the program) we showed some difference in the IBDSCCQ subscale of Contemplation at 6 and 12 months, demonstrating that those who used CBT improved their coping with IBD. However, we failed at demonstrating that a particular dose of CBT is effective as all the comparisons between users and controls were not statistically significant.

Finally, while this trial is the largest to date, it unavoidably has limitations. Its design does not comply with the classic RCT requirements in which participants are aware they may be offered an intervention or the placebo. Given impossibility of blinding the intervention, we decided to withdraw the information regarding the intervention from the controls. Thus, the controls had been informed they participated in an observational study on mental health in IBD. Further, having extensive clinical experience with this population who is in the productive age, often in full-time employment but also frequently caring for young families, we gave participants the option of choosing the mode of CBT delivery. If the study was to be conducted using the classical RCT design, we should have randomly allocated participants to each mode of delivery. In addition, while we conducted the analysis of CBT usage, there is no certainty that our statistics on the online CBT usage are 100% reflective of the actual use. A significant number of patients, particularly, the older ones, preferred to print the materials and work on them offline and thus the short time spent on a given activity may not be a reflection of it not being read or acted on. Perhaps because of it we did not show a significant relationship between CBT usage and the outcomes. Disease activity throughout the trial was measured using disease activity indices and monitoring blood. Future studies could use calprotectin and/or endoscopy to monitor disease activity, although the latter would likely lead to low participation and drop-out due to participant burden. Using calprotectin was not possible in this trial as calprotectin had not been available at the participating hospitals when we commenced the study and the study only received a limited funding. Further, the sample size calculation was prepared for the main group comparisons only and the study was not powered for the subgroup analyses. However, no good estimates for what to base the subanalysis predictions on had been available and the future trials can use the present study data to provide adequate power calculations. Finally, although the attrition in this trial was approximately 30% at 6 months and nearly 40% at 12 months, significantly more CBT users than control group participants withdrew from the study, possibly reflecting the study burden. However, high attrition is a known phenomenon in the self-directed psychotherapy studies for those in the intervention group [18,45], and thus our study does not differ in respect to this from other research in the field.

CBT does not seem to improve disease activity at 12 months since baseline in the unselected patients with IBD although it offers promise to patients ‘in need’. Future studies should direct psychological interventions to patients ‘in need’ and attempt to recruit larger samples to compensate for significant attrition when using online CBT. Longer follow-up is needed to clarify any potential longitudinal effect of CBT in IBD management.