Medications that stimulate gastrointestinal motility primarily through neuromodulation of acetycholine levels include metoclopramide, cisapride, cholinergic agonists (bethanechol), cholinesterase inhibitors (neostigmine), and serotonin agonists. Their efficacy in the treatment of chronic idiopathic constipation is uncertain. Metoclopramide is better for upper gastrointestinal motility disorders, whereas cisapride appears to exert its effect at the level of the colon (162–164).
Behavioral Approaches Behavioral techniques such as biofeedback and bowel regimens may have a role in certain conditions associated with constipation and defecatory dysfunction. Overall, these approaches have far less application to disordered defecation than to fecal incontinence. Biofeedback is important in the treatment of dyssynergic defecation. Relaxation techniques and behavioral modification may be helpful for IBS. Bowel regimens in conjunction with laxatives, suppositories, and enemas can facilitate emptying by optimizing the gastrocolic reﬂex and increased peristaltic activity.
Efficacy of Nonsurgical Treatment Irritable Bowel Syndrome
The most commonly used first-line treatment for the constipation variant of IBS is fiber supplementation and osmotic laxatives. The efficacy of bulking agents for this condition is controversial, and many studies, including meta-analyses, exhibit an effect similar to placebo. There may be benefit to the use of fiber because of the high placebo effect with IBS treatment and lack of serious adverse events associated with its use. However, patients may experience exacerbation of bloating and abdominal discomfort with fiber therapy. Randomized trials and meta-analysis revealed a beneficial effect of polyethylene glycol (MiraLAX) over placebo for the treatment of chronic constipation. In addition, polyethylene glycol was better than tegaserod and lactulose for chronic constipation (165–167). They can be useful as adjunctive treatment options, but can also exacerbate abdominal pain and discomfort. A newer class of drugs, serotonin 5HT4 agonist tegaserod (Zelnorm), stimulates peristalsis, increases colonic motility, decreases intestinal transit times, and reduces visceral hypersensitivity. The recommended dose is 6 mg twice daily. Randomized trials have consistently shown an approximately 10% greater improvement in global IBS symptoms when compared with placebo. Improvement in the bloating and pain symptoms also occurred. No episodes of ischemic colitis or cardiac toxicity have been reported with the use of this medication, and the most common side effects are diarrhea and headache. Cisapride, a 5HT4 agonist with partial 5HT3 antagonist actions, has been withdrawn from use secondary to rare cardiac toxicity. Additional 5HT4 agonists, 5HT3 agonists, and cholecystokinin antagonists are in development (95,96).
Patients with slow-transit constipation tend to respond poorly to fiber supplementation, although most have already tried an empiric trial of fiber before testing to confirm the diagnosis (160). Some patients may benefit from regular toileting, either in the morning or after meals when there is increased colonic motor activity. Biofeedback may have modest short-term benefits, but the long-term effect is questionable (168). Enemas and suppositories can be used in conjunction with bowel regimens. It is also reasonable to attempt a trial of any of the laxatives listed in Table 28.10. Stimulant laxatives are commonly used, but questions remain about the development
Table 28.10 Laxatives for the Treatment of Disordered Defecation
PO, by mouth; PR, per rectum. From Wald A. Approach to the patient with constipation. In: Yamada T, ed. Textbook of gastroenterology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1999:921, with permission.