Selective Serotonin Reuptake Inhibitors (Ssris) for Irritable Bowel Syndrome

In a controlled crossover study 1, 23 non-depressed patients with irritable bowel syndrome (IBS) were recruited from a tertiary care centre for 6 weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) and with placebo, respectively. At 6 weeks, citalopram had significantly improved abdominal pain, bloating, impact of symptoms on daily life and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement.

In a randomized controlled trial 2, 257 patients with severe IBS received either 8 sessions of individual psychotherapy, SSRI antidepressant paroxetine 20 mg daily or routine care by a gastroenterologist and general practitioner. Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life (SF-36 physical component score improvement 5.2 [standard error of mean, SEM 1.26], 5.8 [SEM 1.0], and -0.3 [SEM 1.17]; P < 0.001, respectively), but there was no difference in the psychological component. During the follow-up year, severity and frequency of abdominal pain had improved similarly in all groups, and psychotherapy but not paroxetine was associated with a significant reduction in health care costs compared with treatment as usual.

In a randomized controlled trial 3, 40 non-depressed IBS patients received either fluoxetine 20 mg or placebo for 6 weeks. Patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after the treatment period. At baseline, 21 of 40 patients showed hypersensitivity to rectal distention. Fluoxetine did not significantly alter the threshold for discomfort/pain relative to placebo, either in hypersensitive or in normosensitive IBS patients. Overall, 53% of fluoxetine-treated patients and 76% of placebo-treated patients reported significant abdominal pain scores after 6 weeks (NS). In hypersensitive patients only, fluoxetine significantly reduced the number of patients reporting significant abdominal pain. Gastrointestinal symptoms, global symptom relief, and psychologic symptoms were not altered.

In a randomized controlled trial 4, 81 patients with IBS received either paroxetine (10 or 20 mg) or placebo for 12 weeks. High-fibre diet was instituted in all participants and those not responding to fibre were recruited to the drug trial. In the group continuing on the high-fibre diet only, overall wellbeing improved in 26% patients, and abdominal pain and bloating decreased in 22% and 26% patients, respectively. In the drug treatment groups, overall well-being improved more with paroxetine than with placebo (63.3%vs 26.3%; p= 0.01), but abdominal pain, bloating, and social functioning did not. With paroxetine, food avoidance decreased (p= 0.03) and work functioning was marginally better (p= 0.08). Before unblinding, more paroxetine recipients than placebo recipients wanted to continue their study medication (84%vs 37%; p < 0.001).

In a randomized controlled trial 5, 44 patients with pain and constipation-predominant IBS received either fluoxetine or placebo for 12 weeks. Fluoxetine was significantly more effective than placebo in decreasing abdominal discomfort, relieving feeling and sense of bloating, increasing frequency of bowel movements and decreasing consistency of stool. Mean number of symptoms per patient (Rome II criteria) decreased from 4.6 to 0.7 in the fluoxetine group vs. 4.5 to 2.9 in controls (P <0.001).

In a randomized controlled trial 6, 51 mainly diarrhoea-predominant IBS patients received either imipramine (50 mg), citalopram (40 mg) or placebo. Adequate relief of IBS symptoms was similar for each treatment arm. Improvements in bowel symptom severity rating for interference (P = 0.05) and distress (P = 0.02) were greater with imipramine versus placebo, but improvements in abdominal pain were not. There was a greater improvement in depression score (P = 0.08) and in the SF-36 Mental Component Score (P = 0.07), with imipramine. Citalopram was not superior to placebo.

Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies, heterogeneity in interventions and outcomes) and by imprecise results (limited study size for each comparison).

References

• Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 2006 Aug;55(8):1095-103. [PubMed] http://gut.bmj.com/cgi/content/full/55/8/1095
• Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B; North of England IBS Research Group. The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology 2003 Feb;124(2):303-17. [PubMed]
• Kuiken SD, Tytgat GN, Boeckxstaens GE. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study. Clin Gastroenterol Hepatol 2003 May;1(3):219-28. [PubMed]
• Tabas G, Beaves M, Wang J, Friday P, Mardini H, Arnold G. Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial. Am J Gastroenterol 2004 May;99(5):914-20. [PubMed]
• Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther 2005 Sep 1;22(5):381-5. [PubMed]
• Talley NJ, Kellow JE, Boyce P, Tennant C, Huskic S, Jones M. Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Dig Dis Sci 2008 Jan;53(1):108-15. [PubMed]