Irritable Bowel Syndrome Remains a Difficult Condition to Manage

Nicholas J. Talley, MD, PhD

Disclosures
In This Article

Antidepressants

The tricyclic antidepressants have anticholinergic and central analgesic actions, and they are widely used for patients with moderate to severe IBS who have failed to respond to initial medical therapy.[1,2] A number of randomized controlled trials have evaluated tricyclic antidepressants in the treatment of IBS,[27,28,29,30,31,32] and meta-analyses support their efficacy.[33,34] The highest-quality trial available was conducted by Drossman and colleagues[35] but was not included in the previously mentioned meta-analyses: in a comparison of desipramine versus placebo in patients with IBS, a benefit with desipramine was reported. Overall, there was a 60% response to desipramine compared with a 47% response to placebo by the intention-to-treat analysis, although this difference was not significant; the per-protocol analysis, however, did show a significant benefit (number needed to treat, 5).[35]

All of the other trials have been small and of variable quality. One meta-analysis showed tricyclic antidepressants were superior to placebo (number needed to treat, 3).[34] However, the ACG Task Force concluded that the evidence was inadequate to support the effectiveness of tricy clics for improvement of global IBS symptoms despite the fact that pain seemed to improve.[3] It is also unclear whether some bowel-pattern subgroups respond better than others to a tricyclic. Drossman and coauthors[35] reported that patients who have IBS with diarrhea and more severe IBS symptoms were more likely to respond positively to desipramine. Despite the strong clinical impression that this class of drugs is useful, the exact benefit remains controversial.[3,33,34,35]

The selective serotonin reuptake inhibitors (SSRIs) have been much less studied in IBS. Results of one report were that paroxetine was superior to usual care in IBS in terms of improving some quality-of-life components; but the effect on pain was limited, and the lack of a placebo control group inhibits interpretation of these data.[36] In another study, 40 patients with IBS were randomized to receive fluoxetine (20 mg) or placebo.[37] After 6 weeks, 76% of persons taking placebo still experienced abdominal pain compared with 53% of those taking fluoxetine, but this finding was not significant.[37] Also, global symptoms did not change significantly.[37] Despite the lower rate of side effects for SSRIs and their widespread use by IBS patients, the evidence base for this class of agents remains inadequate.[1,38] Furthermore, there are no head-to-head trials comparing tricyclic antidepressants with SSRIs to date.

Anxiolytic agents have seldom been tested in IBS, although some small, older trials suggested possible benefit.[1,2] However, habituation and interaction with other drugs have limited their use. Thus, use of anxiolytic agents in patients with IBS is not recommended.

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