LAUSR

Functional dyspepsia (FD) is a chronic functional disorder of the upper gastrointestinal (GI) tract affecting approximately 10–20% of the global population. As there is no cure, its persistent symptoms are recognized to have a significant impact from a societal and quality of life perspective. The mainstay of therapy has been directed at the upper GI tract in the form of acid suppression (proton pump inhibitors) and prokinetic agents, but these medications have been shown to benefit only 30% of FD patients at best. The modest effects of a purely “gut-directed” pharmacotherapy are due to the fact that the pathophysiology of FD is complex and heterogeneous, involving bidirectional pathways between the upper GI tract and the brain. The gut and brain communicate through the enteric nervous system and the hypothalamic–pituitary–adrenal axis. Epidemiological studies have demonstrated that individuals with anxiety are eight times more likely to develop FD compared with those without any psychological morbidity. Stress and anxiety are recognized to cause a disordered gut–brain axis, leading to alterations in GI motility and enhanced visceral hypersensitivity. For this reason, pharmacological agents such as tri-cyclic antidepressants, with their central and peripheral neuromodulating action, have been shown to be effective in some patients with FD. Mirtazapine, an antidepressant and antagonist of the histamine receptor H1, the α2 adrenergic receptor, and the serotonin receptors 5-HT2C and 5-HT-3, has been shown to improve symptoms and weight loss in FD. However, anti-psychotropic drugs have been associated with considerable adverse events, which limit their widespread use in FD. At present, pharmacological-based therapies which can modulate a disordered gut–brain axis without significant adverse effects in FD appear to be lacking. Psychological therapies are defined as non-pharmacologic, talking-based approaches aimed at treating diseases of mental health. The most often used therapy is that of cognitive behavioral therapy (CBT), which is a short-term form of psychotherapy that focuses on stressful problems that come up in a patient’s day-to-day experiences. In this issue of JGH, two articles demonstrating the efficacy psychological therapies in FD have been published. A systematic review and meta-analysis by Rodrigues et al. identified nine randomized controlled trials (RCTs) comparing various psychotherapies against a control (mainly acid suppressive pharmacotherapy). Although there was considerable heterogeneity among the studies, the random effects meta-analysis showed a significant improvement in FD symptoms favoring psychological therapy compared with control treatment. Most of the psychological interventions were either CBT or derivatives of it. In a single-center pilot RCT, Teh et al. compared the efficacy of mindfulness-based CBT and standard pharmacological therapy for 8 weeks in 28 FD patients. The results showed a trend towards subjective FD symptom improvement and significant improvements in the short-form Nepean Dyspepsia Index and the Depression/Anxiety/Stress scale. The reports from both these articles indicate that psychological therapy may be more effective than gut-directed pharmacotherapy in FD. Interestingly, the benefit of psychological therapy has been shown in other disorders of the gut–brain axis such as irritable bowel syndrome. However, a major concern with RCTs of psychological therapy in FD is the lack of appropriate control groups. It is well recognized that greater communication and support provided in psychological therapy regimens, compared with limited contact time with a doctor in standard therapy, may result in a placebo effect in FD. The placebo effect in functional GI disorders is well recognized, and it has been shown to lead to considerable symptom and even GI motility improvement in FD. Three studies included in the meta-analysis by Rodrigues et al. performed a sham-type intervention as a control, but the lack of such controls in the other six studies and in the pilot RCT by Teh et al. may have led to a performance bias for psychological therapy in FD. Despite some of these concerns, the evidence for the efficacy of psychological therapy in FD is encouraging. However, there are several major challenges to its implementation in clinical practice. Psychological therapies are time-intensive (between 1.5 and 2 h per week sessions) and require active participation by the patient (e.g. homework assignments). Approximately 20% of patients dropped out from the pilot RCT by Teh et al., due to time commitments and difficulty in following instructions. The availability of psychologists is lacking, but multidisciplinary clinics have been suggested as an alternative. However, most importantly would be the acceptance of this therapy by patients with FD, who are often unable to perceive a “non-organic” cause for their symptoms. In the study by Teh et al. again, 50% of FD patients who were eligible declined to participate in the study, presumably for this very reason. Thus, it appears that psychological therapy will likely be reserved for a subset of willing FD patients, who have the time and commitment to completing it.