Extra digestive manifestations of irritable bowel syndrome: intolerance to drugs?

Patients with IBS frequently complain of medication side effects. The goals of this study were to assess the prevalence of drug intolerance as an extra GI manifestation in patients with IBS and to verify the association between drug intolerance and psychological comorbidity. Female patients followed in a tertiary care center completed questionnaires assessing the presence of drug intolerance as well as somatic and psychological extra GI conditions. IBS patients (Rome II criteria; n = 71) were compared to inflammatory bowel disease patients (IBD; n = 96) or to healthy controls (HC; n = 67). The relationship to psychological comorbidity was verified in two different paradigms: (1) by looking at the statistical correlation between drug intolerance and the psychological extra GI symptoms in our IBS patients, and (2) by comparing in a meta-analysis the side effects to placebo (the nocebo effect is presumably increased due to hypervigilance or amplification in psychological disorders) in IBS patients or in patients with comparable medical conditions included in various drug trials approved by Health Canada. Our results show that prevalence of drug intolerance was significantly more elevated in IBS (41% patients) than in HC (7%) or in IBD (27%); somatic and psychological extra GI symptoms were also markedly increased in IBS. In addition, drug intolerance in our IBS patients was significantly associated with somatic comorbidities such as fatigue or multiple symptoms (P < 0.001), but not with psychological factors such as depression, anxiety, mood instability, or sleep disorder. A meta-analysis revealed that the nocebo effect was not different in patients with IBS than in control patients. In conclusion, drug intolerance is a frequent extra GI manifestation of IBS that is not associated with psychological comorbidity; thus, a somatic origin must be explored.