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Is amitriptyline really effective in diarrhoea‐predominant irritable bowel syndrome?

Is amitriptyline really effective in diarrhoea-predominant irritable bowel syndrome? SIRS, Vahedi et al. reported that amitriptyline is effective in diarrhoea-predominant irritable bowel syndrome (IBS). Such a claim is weakened by several methodological weaknesses. One of the reasons invoked for performing a new clinical trial with an antidepressant in IBS, apart from evaluating a lower dosage of amitriptyline, is that most previous studies had a small sample size. It is therefore surprising that Vahedi et al. included only 50 patients, whereas in most circumstances several hundred of patients are needed. Six IBS symptoms with binary answers were self-assessed daily during 2 months. The definition for a complete response (absence of all symptoms) remains unclear: does that mean absence of symptoms only on the last day of the study, or a repeated absence of symptoms during several days (how many days? consecutive or not?)? Diarrhoea-predominant IBS was not defined. If based on more than three bowel movements per day or on loose stools, then at maximum, only 76% (placebo) and 84% (amitriptyline) of patients had such a diagnosis at baseline. The authors reported comparability of groups at baseline. However, there was not enough power with only 50 patients to show any statistical difference. Indeed, there is a clinically relevant difference between groups for age (6 years difference), duration of IBS (7 years), presence of flatulence (24%), and loose stools (16%). The mean score of the six symptoms, although similar at baseline, is made of different symptoms between placebo and amitriptyline. This precludes any statistical analysis, on the mean score and on most of the symptoms. However, there was no statistical difference between groups on abdominal pain. Recent meta-analyses challenge the efficacy of antidepressants. 3 The Cochrane review did not demonstrate benefit for global assessment or abdominal pain. Several studies included in other meta-analyses were excluded from this review because of major methodological weaknesses. It is well established that smaller studies are, on average, conducted and analysed with less methodological rigour than larger studies and tend to show larger effects. 6 Given these above major flaws, it is unlikely that amitriptyline is superior to placebo by a 40% difference on complete response, as shown by Vahedi et al. O. CHASSANY* & M. DURACINSKY *Département de la Recherche Clinique, Assistance Publique – Hôpitaux de Paris & Université Denis-Diderot, Paris; Service de Médecine Interne, Hôpital Bicêtre, Assistance Publique – Hôpitaux de Paris, Kremlin-Bicêtre, France. E-mail: olivier.chassany@sls.aphp.fr