Chronic constipation is an undertreated disorder. Only 26% of patients meeting the Rome II diagnostic criteria for this condition are thought to seek medical attention.

Many patients mistakenly believe that constipation is a temporary and personal problem rather than a medical problem. In addition, the social stigma and embarrassment surrounding discussions of bodily functions may deter some people from seeking medical help. Attempts to self-treat with over-the-counter products resulted in slightly more than $700 million in sales of laxatives in 2004.

For those who do eventually seek medical care for this disorder, there are currently three treatment options: lifestyle and dietary changes, pharmacological treatments, and bio-feedback.

Lifestyle and Dietary Alterations

Lifestyle adjustments are typically suggested as a first line of treatment; these usually entail an increase in fluid intake, fiber consumption, and exercise. There is a shortage of adequately controlled trials evaluating the efficacy of these lifestyle changes. Habit training to achieve a regular bowel movement schedule has been studied primarily in children. Increasing fluid intake does not appear to affect stool volume output, probably because most of the ingested water is absorbed in the small intestine before it can enter the colon. Similarly, regular exercise (as perceived by the average person) has no established link to constipation relief.
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Dietary fiber, believed to alleviate constipation by improving gastrointestinal transit and producing larger, softer stools, can be increased with the addition of high-fiber foods (such as vegetables and whole grains) to the diet or by taking commercially available supplements. Unfortunately, increasing fiber has a tendency to cause undesirable side effects, such as bloating and increased flatulence, that make long-term patient compliance less likely.

Pharmacological Agents

 

Bulking Agents

Bulking agents are concentrated forms of fiber and are composed of naturally occurring psyllium or synthetic poly-saccharides or cellulose derivatives. They add water and additional solid material to stool, which may improve chronic constipation in a manner similar to that of fiber naturally contained in the diet. Fluid intake should be increased. The side effects are similar to those associated with dietary fiber (i.e., bloating and flatulence).

Osmotic Laxatives

Osmotic laxatives are hypertonic agents that draw water into the colon. They include saline laxatives such as magnesium hydroxide (milk of magnesia) and sodium phosphate (phosphate soda). Both oral and rectal forms of sodium phosphate (such as a Fleet enema) are available. However, a small amount of magnesium and phosphate is actively absorbed in the small intestine, and hypermagnesemia and hyperphosphatemia can occur, especially in patients with renal failure.

Other osmotic laxatives include lactulose, sugar alcohols (sorbitol or mannitol), and polyethylene glycol (PEG).

Lactulose is a synthetic disaccharide that is broken down by bacteria in the colon to yield organic acids and carbon dioxide to lower the pH and soften the stool. The main disadvantages of lactulose are abdominal distention, flatulence, and its overly sweet taste.

Sorbitol and mannitol, like lactulose, are poorly absorbed in the small intestine and produce abdominal distention and flatus.

Polyethylene glycol is an inert polymer that is not absorbed by the gut; it is excreted unchanged in the feces. It opposes the absorption of water, which results in loose stools. The PEG solution is formulated alone or with electrolyte solutions. It is commonly used for bowel cleaning before colon-oscopy (e.g., CoLyte, Schwarz; GoLytely, Braintree Labs). Smaller-dose packets are available and are used in the treatment of constipation (e.g., MiraLax, Braintree Labs).

A sufficient amount of water must be used with MiraLax to avoid dehydration. It is recommended that 250 ml of water ingested with 17 g of MiraLax, although it might be difficult for some patients to consume this much water. This osmotic laxative is indicated for short-term, intermittent use only (up to two weeks). Nausea, abdominal bloating, cramping, and flatulence may occur with PEG formulations. Prolonged, frequent, or excessive use of PEG solutions may lead to electrolyte imbal-ance.

Glycerine is an osmotic agent that is absorbed well in the small intestine and is therefore used as a suppository. It draws water into the rectum to produce a bowel movement.

Stimulant Laxatives

Stimulant laxatives not only stimulate intestinal motility but also affect mucosal transport. Examples include docusate sodium (Colace), diphenyl methanes (bisacodyl), anthraquinones (Cascara sagrada and senna), and castor oil. The docusates were designed to lower surface tension and soften the stool. They also stimulate intestinal fluid and water secretion. In a placebo-controlled study, docusate had no effect on stool weight, stool frequency, stool water, or mean transit time.
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Bisacodyl is available in both tablet form and as suppositories. The laxative effect of the anthra-quinones is secondary to net water secretion and the stimulation of colon motility. The side effects of stimulant laxatives include abdominal cramping and melanosis coli with anthraquinones.

A randomized double-blind, placebo-controlled, crossover study in patients with chronic idiopathic constipation demonstrated that colchicine increased the number of bowel movements and accelerated colon transit time compared with placebo. Abdominal pain was more common in the treatment group. Similarly, misoprostol stimulates intestinal transit time and has been shown to be effective in the treatment of chronic constipation. However, side effects can be a limiting factor in the use of these agents for long-term therapy.

Limitations of Current Treatments

Both physicians and patients are aware of the limitations of the current laxative treatment options for chronic constipation (Figure 3). In a 2004 report, 91% of primary care physicians expressed a wish for better treatment options for constipation. Only 50% of patients being treated for chronic constipation were satisfied with their current laxative treatment. Taken together, these statistics demonstrate the need for more satisfactory therapeutic options.
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FIGURE 3 Level of satisfaction with laxative treatment options

FIGURE 3 Level of satisfaction with laxative treatment options.

Ideal treatments would address the lack of consistent efficacy and potential side effects associated with these agents, such as electrolyte imbalance. They would also be available to the large numbers of patients with chronic constipation, independent of age or sex.