An updated systematic review and meta-analysis [ 31 ] identified 17 separate trials of antidepressants with an overall beneficial effect on IBS symptoms: RR of remaining symptomatic 0.67 (95% CI 0.58 to 0.77), and an NNT of 4. However, only three of the RCTs were of high-quality—the majority of trials were conducted in secondary or tertiary care, and there was evidence of heterogeneity between studies and possible publication bias. In addition, two of the studies conducted in Iran, may have been atypical with placebo response rate of 14% [ 32 ], or “complete” response to amitriptyline of 63% [ 33 ], which seems unusually high. Therefore, the estimated NNT of 4 for the antidepressant class may be overestimated in this meta-analysis.

Antidepressant efficacy appears more convincing for TCAs, with an NNT of 4 and no heterogeneity between the 11 studies, compared with SSRIs with an NNT of 4 but significant heterogeneity between the seven trials. Seven RCTs (with 182 patients on antidepressants and 169 patients on placebo) reported the effect on abdominal pain, and the RR of abdominal pain persisting was significantly lower compared with placebo (0.62; 95% CI 0.43 to 0.88); however, there was considerable heterogeneity between studies (I= 72.4%). Effectiveness according to IBS subtype has only been assessed in two RCTs to date [ 32 33 ]. It is unclear whether the efficacy of antidepressants in IBS results from the treatment of co-existent depression. Three of the identified studies reported that there was no correlation between improvement in IBS symptoms and depression scores [ 34 36 ], and a fourth trial reported that the benefit of desipramine (a TCA) was greater in non-depressed individuals [ 37 ]. However, in an RCT by Ladabaum and colleagues [ 38 ], which excluded participants with depression, there was no benefit of citalopram. A 12-week, open-label trial of the SSRI, duloxetine, was conducted in 13 subjects with IBS and generalized anxiety disorder and showed improvement in overall and severity scales of IBS as well as symptoms of anxiety and QOL [ 39 ]. Effectiveness of antidepressants in relation to co-existent anxiety or other mental health conditions was seldom assessed in the literature. For example, beneficial therapeutic effect of citalopram was independent of effects on anxiety [ 35 ]. However, cognitive factors (sense of control over the condition, positive relationship with therapist or study coordinator, confidence in treatment, improvement in maladaptive cognitions, and quality of life during treatment) were all significant predictors of treatment response to medical and psychological treatments (deipramine, education and cognitive behavioral therapy) in functional bowel disorders, in contrast to demographic and other clinical variables which were not predictive [ 40 ].