What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans.

Background: Clonidine is considered an alternative treatment for refractory diarrhoea. The evidence in the literature is scarce and not conclusive. The present paper's purpose is to gather available evidence and provide a systematic answer regarding the effectiveness of clonidine for diarrhoea. Method: We performed a systematic review of clonidine and its effect on diarrhoea. Meta-analysis was performed with a random effects model of the standardized mean difference (SMD) or the weighted mean difference and heterogeneity was quantified with I-2 and publication bias was assessed with Egger's and Begg's test. Subgroup analyses and meta-regression were performed to investigate sources of heterogeneity. Any empirical study describing use of clonidine for diarrhoea in humans independent of age was included. For the meta-analysis, papers had to provide sufficient data to produce an effect measure, while case reports were not included in the meta-analysis and are discussed narratively only. Results: A total of 24 trials and seven case reports were identified. Clonidine (median dose 300 g/day) has been used for treatment of diarrhoea in irritable bowel syndrome, faecal incontinence, diabetes, withdrawal-associated diarrhoea, intestinal failure, neuroendocrine tumours and cholera; studies were also performed on healthy volunteers. Results indicate a strong effect of clonidine on diarrhoea (SMD = -1.02, 95% confidence interval [CI] -1.46 to -0.58) with a decrease of stool volume by 0.97 l/day, stool frequency by 0.4 times/day and increase in transit time by 31 minutes. In a sensitivity analysis of studies with functional diarrhoea and sample size over 10 subjects, the effect was similar -0.99 (95% CI -1.54 to -0.43). There is however significant heterogeneity and publication bias. Heterogeneity decreased in subgroup analyses by condition but not with other factors examined. A limitation of the present study includes small study effects. Conclusion: Clonidine is effective for treatment of diarrhoea and should be considered as an alternative when all other medications have failed.