Expert commentary--new developments in the treatment of constipation.

Most available treatments for constipation have not been tested. In 2002, Jones and colleagues[1] reported their meta-analysis of published evidence on the efficacy of laxatives in constipation. They found a lack of large, well-controlled published studies. In fact, their experience led them to conclude that there is no “unequivocal evidence that laxatives are actually an efficacious treatment of chronic constipation.” A systematic review by Tramonte and colleagues[2] in 1997 concluded that the actual indications and benefits of laxative therapies were poorly characterized. In the elderly, there have been even less comparative studies, and trials have been so small that the UK National Health Service Center for Reviews and Dissemination Health Technology Assessment Programme similarly found it difficult to determine what constitutes effective treatment of constipation.[3] Indeed, most available treatments for constipation have not been tested in modern, well-designed studies and their use depends more on “custom than science.”[4,5] Drugs in development and recently introduced to the therapeutic armamentarium for constipation bring a new scientific rigor to the field. Table 1 lists most of the currently available and investigational laxatives; some of the more common agents used in this setting are herein discussed. Tegaserod, a 5-HT (hydroxytryptamine)4 receptor agonist, recently received US Food and Drug Administration (FDA) approval for the treatment of chronic constipation. No other agent has yet been approved for treatment of chronic constipation. The meta-analyses have shown, in general, that fiber and laxatives increase bowel movement frequency compared with placebo.[2,3] Fiber has been shown to consistently decrease abdominal pain and improve stool consistency. Cisapride, lactulose, and lactitol have been shown to improve stool consistency, and reviews show inadequate evidence to establish whether fiber is superior to laxatives or whether one laxative class is superior to another (cisapride was withdrawn from the market because of cardiac side effects of “torsades de pointes,” particularly when used in combination with antibiotics such as macrolides).[2] Table 1 Laxatives New Developments Polyethylene Glycol Laxative High-molecular-weight polyethylene glycol (PEG) obligates intraluminal water and has been used with success for treatment of constipation.[6] PEG 3350 laxative is a large, chemically inert polymer with substantial osmotic activity. It does not contain any salt that can be absorbed, as can occur when using PEG electrolyte solutions. One hundred and fifty-one subjects were enrolled in a 14-day trial involving this agent. Bowel movement frequency, stool consistency, ease of passage of stool, and effectiveness, as rated by investigators and study subjects, were improved after treatment with PEG 3350 compared with placebo.[7] Other work[6] and a Cochrane Review-based meta-analysis of “high-quality” studies[8] confirm the safety and efficacy of PEG laxative for the treatment of constipation. Additional long-term comparative trials and studies comparing PEG laxative with other laxative products are currently in progress.