Review Article: The Role of Serotonergic Agents in the Treatment of Patients With Primary Chronic Constipation

Conclusion

Our understanding of the pathophysiology of chronic constipation continues to evolve. Serotonin appears to play an important role in a number of physiological functions relevant to the symptoms of chronic constipation. As a consequence, drugs that accentuate the effects of serotonin, such as the 5-HT₄ receptor agonists, are attractive treatment candidates for patients with chronic constipation. Of the 5-HT₄ agonists that have been developed, tegaserod has been shown to accelerate gut transit and to improve the symptoms of chronic constipation while it retains an attractive safety profile in recent large, methodologically rigorous clinical trials. Although the exact mechanisms for these benefits remain unclear, it appears that the promotility effect of tegaserod, rather than its prosecretory effects or its amelioration of heightened visceral sensation, are largely responsible for the clinical effects of this medication. Although clearly superior to placebo, tegaserod improves symptoms in only a subset of patients with chronic constipation. This suggests that serotonin plays a critical role in some, but not all, patients with chronic constipation. Though unproven, it may be that patients with subtle or overt pelvic floor dysfunction are less likely to respond to serotonergic agents than patients with normal or delayed colonic transit. The roles of other serotonergic agents, including the 5-HT₃ agonists, the mixed 5-HT₃ antagonists/5-HT₄ agonists and agents that affect SERT, in the treatment of patients with chronic constipation remain to be determined.

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The authors would like to acknowledge the editorial assistance of Maribeth Bogush PhD and Sophia Shumyatsky, PharmD, in the preparation of this manuscript.

Aliment Pharmacol Ther. 2005;22(11):1047-1060. © 2005  Blackwell Publishing