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We read with great interest the letter by Van Kerkhoven et al (this issue) concerning a recent article published by our group (Gut 2006;55:1095–103). We thank the authors for their interest in our work. In this study, we found that treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram markedly improves symptoms, including abdominal pain, compared with placebo in non‐depressed patients with irritable bowel syndrome (IBS). Moreover, this effect on core IBS symptoms was found to be independent of effects on anxiety and depression as measured by self‐report questionnaires.
We agree that there are several previous studies investigating the effect of tricyclic antidepressants on functional gastrointestinal disorders.1,2 However, although SSRIs are widely used in the treatment of IBS in clinical settings, there is a paucity of randomised controlled trials studying their effectiveness in this indication, as pointed out in our study, by Dr Creed in his commentary to our study and also in recent excellent reviews regarding this topic.1,2,3 Only four previous trials have been identified by Creed, and by ourselves in the Discussion section of the article. Moreover, we believe that this study may be important as it is one of the first to show a considerable effect not only on overall well‐being and quality of life but also on core IBS symptoms including abdominal pain and bloating. Furthermore, this was observed in a study that excluded patients with high anxiety and depression levels.
We agree that this study has important limitations, as dealt with in the discussion section of the original article, and reiterated in the commentaries by Creed and in the letter by Van Kerkhoven et al. We agree that the analysis of the first phase as a parallel group design study in a smaller patient group and the recruitment of patients from a tertiary care setting are all limitations. However, the study was principally designed to provide mechanistic insight into the mode of action of SSRIs; it was not designed to be the definitive clinical study. Therefore, we excluded patients with high anxiety and depression levels and we performed assessments of the effect of the SSRI on colonic sensorimotor function. Hence, although the number of patients included in this demanding trial is small, the patients were exceptionally well characterised in terms of symptoms, colonic sensorimotor function and psychosocial profile. Moreover, the participation rate throughout the study remained high, and the study remained double blind throughout its long course. The cross‐over design was also chosen to allow close correlation of (effects of citalopram on) colonic sensorimotor function and symptomatic outcome. As such, this study is the first one to show efficacy on core IBS symptoms, which cannot be attributed to peripheral effects in colonic sensorimotor function, nor to effects on anxiety, depression or somatisation.
It is crystal clear that this needs confirmation in a larger, placebo‐controlled parallel group trial in a non‐tertiary care setting, as we already indicated in the final sentence of the paper: “Larger scale studies will be required to study the efficacy of citalopram or other SSRIs in the IBS patient population seen in primary practice and in secondary care”. When designing such a large trial, our study provides important insights on which symptoms to assess, what dose of citalopram to use, which symptoms respond over which time course of response, and shows that results can be obtained even when excluding patients with high anxiety or depression levels. However, it is generally extremely difficult to obtain funding for therapeutic trials in patients with functional bowel disorders with existing psychotropic drugs, and we believe this is the main reason that such information is lacking. If Van Kerkhoven et al were to succeed in organising such a large multicentre trial, we would be more than happy to contribute by including carefully selected and well‐characterised patients with IBS.
Competing interests: None.