Meta-Analysis: The Treatment of Irritable Bowel Syndrome

Mechanism of Action: Two-thirds of patients perceive their IBS symptoms as food-related.^[8] Postprandial worsening of symptoms^[171] as well as intolerance to one or more nutrients^[172] are commonly described by IBS patients. Several pathological mechanisms may be responsible for this intolerance, such as visceral hypersensitivity,^[173,174] motility disturbances,^[175] sugar malabsorption,^{[176,177,178]} gas-handling disturbances^[41,179] and abnormal colonic fermentation.^[39,40] However, anxiety or depression greatly affect the reporting of food-related symptoms.^[8,180] This speaks, at present, against a major role of food intolerance in the pathogenesis of IBS.

Clinical Evidence: Elimination diets in IBS have yielded conflicting results.^[181] Identifying offending dietary substances, e.g. lactose, caffeine, fatty foods, alcohol, gas-producing foods, sorbitol, etc. can help some patients^[182] but overly zealous dietary restrictions are harmful, as patients may begin a process of dietary elimination that can lead to severely unbalanced nutrition or an obsessive preoccupation with diet.

Mechanism of Action: The rationale for the use of probiotics in IBS is its association with infectious diarrhoea. It is generally accepted that IBS-like symptoms are highly prevalent in the months after cure from infectious enteritis, in particular associated after travel to tropical countries. About 7-30% of patients with infectious diarrhoea can develop IBS.^{[6,183,184,185]} Inflammatory infiltration of the intestinal mucosa was observed in IBS subjects after infectious gastroenteritis^[6,186] as well as in other IBS patients.^[187] Among the possible mechanisms of probiotic therapy is the promotion of the endogenous defence barrier of the gut. These include normalization of increased intestinal permeability and altered gut microecology as well as improvement of the intestine immunological barrier.

Clinical Evidence: Some probiotics, including acidophilus or bifidus milk, were reported to relieve constipation in an uncontrolled study with a small number of patients.^[188] In a randomized, placebo-controlled study, probiotics containing Saccharomyces boulardii decreased functional diarrhoea but did not influence other IBS symptoms.^[189] Several recent, double-blind placebo-controlled studies showed no effect of probiotic preparations on symptoms or bowel habit in IBS-D^[190] or IBS-C subjects.^[191] In other studies, probiotics were more efficient than placebo in relieving IBS symptoms.^{[192,193,194]} However, these studies suffer from methodological inadequacies, including a small number of patients, low compliance and poor statistical analysis. Thus, there is not enough clinical evidence to recommend the use of probiotics in the treatment of IBS.

Mechanism of Action: Psychological factors such as stressful or traumatic life events are reported by up to 60% of IBS patients, and are associated with the first onset of symptoms or with symptom exacerbation^[7,195] (Figure 1). Harmful events such as abuse, neglect or loss of a parent have been described in IBS patients^[196,197] and, to a certain degree, also in animals models.^[198] The aggregation of IBS in families of patients with IBS might also be due to learned responses which are transmitted in early childhood.^[3] These responses may imply a tendency towards anxiety, depression and somatization.^[196]

Thus, it has been suggested that reducing the severity of psychological distress by will alleviate the symptoms of IBS. Psychotherapy, such as cognitive-behavioural therapy,^[199] dynamic/interpersonal psychotherapy, hypnotherapy,^[200] and stress management^[201] may reduce autonomic arousal and anxiety and thus reduce the frequency and severity of symptoms.

There are a number of pathophysiological studies directly evaluating the effect of psychotherapy on GI motility or visceral sensitivity. Most of these studies are related to hypnotherapy. Some controlled studies with IBS patients reported reductions in fasting colonic motility^[202] or improvements in abnormal sensory perception in IBS patients^[203,204] with hypnotherapy compared with no treatment or supportive psychotherapy. However, others failed to find such an effect and attributed the improvement of IBS symptoms to reduction in psychological distress and somatization by psychotherapy.^[205]

Clinical Evidence: There have been numerous trials of psychological treatment in IBS. Many suffer of methodological inadequacies.^[206] The main problem of these studies are the absence of a true control group and lack of adequate blinding, leading to a bias assessment.^[206]

For example, hypnotherapy was reported to improve IBS symptoms compared with supportive psychotherapy^[207], symptom-monitoring wait-list condition^[208] or no treatment.^[209] However, some measures such as the therapist contact time or degree of attention to symptoms are lower with these therapeutic procedures than with hypnotherapy. Thus, given the generous placebo response that accompanies trials of functional bowel disorders,^[130] the absence of adequate control groups may account for the favourable effect obtained with psychotherapy.^[206] Accordingly, in a adequately controlled trial in IBS subjects comparing cognitive behaviour and relaxation therapy to standard care alone showed a reduction in anxiety, depression, social functioning scale and bowel symptoms, with, however, no difference between the three approaches.^[210] In addition, similar therapies have been successfully used in organic disorders such as breast cancer.^[211] Thus, this type of therapy might simply modify illness behaviour, thus improving the handling of the disorder by the patient. Moreover, while some therapies such as cognitive behaviour therapy, appear efficacious in IBS patients, they are not cost-effective.^[212] In conclusion, the role for psychotherapy in IBS has not been established.^[206]