Original Articles
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,☆☆,,★★

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Abstract

Background & Aims: Although widely prescribed, the evidence for the use of antidepressants for the treatment of irritable bowel syndrome (IBS) is limited. In this study, we hypothesized that fluoxetine (Prozac), a selective serotonin reuptake inhibitor, has visceral analgesic properties, leading to increased sensory thresholds during rectal distention and improvement of symptoms, in particular in IBS patients with visceral hypersensitivity. Methods: Forty non-depressed IBS patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after 6 weeks of treatment with fluoxetine 20 mg or placebo. Abdominal pain scores, individual gastrointestinal symptoms, global symptom relief, and psychologic symptoms were assessed before and after the intervention. Results: 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 (19 ± 3 vs. 22 ± 2 mm Hg above MDP) or in normosensitive (34 ± 2 vs. 39 ± 4 mm Hg above MDP) IBS patients. Overall, 53% of fluoxetine-treated patients and 76% of placebo-treated patients reported significant abdominal pain scores after 6 weeks (not significant). In contrast, 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. Conclusions: Fluoxetine does not change rectal sensitivity in IBS patients. Possible beneficial effects on pain perception need to be confirmed in larger trials.

Section snippets

Study subjects

Forty patients with IBS (18 men and 22 women; age, 18-59 years; mean age, 40 ± 2 years) participated in the study. On the basis of their clinical history, 16 of 40 (40%) patients were considered as having diarrhea predominant, 11 of 40 (28%) constipation predominant, and 13 of 40 (32%) alternating type IBS. The mean duration of symptoms at entry was 5.9 ± 1 years (range, 0.3-27 years). All patients had been unsuccessfully treated previously; 32 (80%) had received bulking agents, 24 (60%)

Pressure sensitivity

In HV, MDP was 6 ± 1 mm Hg. Thresholds for first sensation, urge, and discomfort/pain during phasic, isobaric distention were 6 ± 1, 14 ± 2, and 39 ± 3 mm Hg above MDP, respectively (Table 1). The lower limit of normal for discomfort/pain, defined as the 10th percentile of the threshold for discomfort/pain in HV, was 25 mm Hg (Figure 1).

. Individual thresholds (mm Hg above MDP) for discomfort/pain during phasic, isobaric rectal distention in 12 HV and 40 IBS patients with no active treatment

Discussion

Our study demonstrates that fluoxetine has no effects on visceral sensitivity, questioning its visceral analgesic properties in nondepressed IBS patients. In addition, no effect on IBS symptoms could be demonstrated in the entire group of treated patients. However, in patients with hypersensitivity to rectal distention, fluoxetine reduced the number of patients reporting significant abdominal pain, which was not observed in patients with normal rectal sensitivity. Future, larger clinical trials

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    Address requests for reprints to: Guy Boeckxstaens, M.D., Ph.D., Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. e-mail: [email protected]; fax: (31) 20-691-7033.

    ☆☆

    Sponsored by Eli Lilly and Company, the Netherlands, and supported by a grant from the Netherlands Digestive Diseases Foundation (MLDS), grant number WS 99-38 (to S.D.K.).

    Parts of the study have previously been published in abstract form (Gastroenterology 2002;122:A551).

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