To the Editor:
Constipation has been defined as a frequency of defecation of twice weekly or less with lumpy or hard stools (Eastwood & Avunduk, 1994). Functional constipation, a common clinical condition (Eastwood & Avunduk), is defined by the presence of two or more of the following symptoms according to the Rome criteria: sensation of blockage during defecation, lumpy or hard stool, sensation of incomplete evacuation, and fewer than three bowel movements per week (Thompson, Longstreth, Drossman et al., 1999). Rome-2 criteria added the need of "the presence of constipation during previous 12 weeks and no structural or biochemical etiology can be defined during consecutive 12 weeks" (Thompson et al.).
Constipation is not the name of an illness; it is only a symptom. It may be functional, or it may be associated with organic diseases in which bowel movements may be affected (Eastwood & Avunduk, 1994;Verne, Eaker, Davis, & Sninsky, 1997). Lifestyle variables such as diet and exercise are believed to play an important role in the etiology of functional constipation. In the treatment of functional constipation, routine laxatives have been the most commonly used medications in addition to lifestyle changes (Eastwood & Avunduk). Unfortunately, functional constipation frequently does not respond to these routine therapeutic measures.
Routine laxatives can provide a satisfactory result in long-term use only in the minority of patients with functional constipation (Loening-Baucke, 1995). It is known that colchicine stimulates intestinal motility and commonly causes diarrhea in patients taking the drug for either gouty arthritis or familial Mediterranean fever (Ehrenfeld, Levy, Sharon, Rachmilewitz, & Eliakim, 1982). The first study of colchicine in the treatment of constipation was from Sandyk and Gillman. They used colchicine in the treatment of constipation in patients with Parkinson's disease and found it was effective for this purpose (Sandyk & Gillman, 1984). Recently, more authors have been interested in this subject (Frame, Dolan, Kohli, & Eberly, 1998;Verne, Eaker, Davis, & Sninsky, 1997).
We aimed to study the efficacy of colchicine in the treatment of patients with functional constipation who were refractory to routine laxative therapy. Patients with the pathologies that may affect the bowel movement and colonic transit were excluded from our study. We also excluded patients with a history of previous abdominal surgery and patients on long-term medication.
Patients with functional constipation were advised of recommended lifestyle changes and given laxatives such as lactulose, short-term enemas, senna glycosides, or phenolphthalein for 8 weeks. Patients with a frequency of defecation less than three times a week after this routine treatment were identified as resistant cases and were then treated with oral colchicine 0.5 mg three times a day for 12 weeks. Twenty-one patients (13 male, 8 female) with chronic functional constipation resistant to laxatives were enrolled into our study. The mean number of spontaneous bowel movements were 1.2 +/- 0.7 per week initially, and 1.7 +/- 0.9 per week during routine therapy of constipation with laxatives and enemas. The mean number increased to 5.2 +/- 1.3 per week after 12 weeks of colchicine treatment (p <.05) (Figure 1).
Some adverse effects were seen during therapy with laxatives and enemas like abdominal pain (28.5%), bloating (38%), meteorism (33.3%), nausea (14.2%), and vomiting (9.5%). These symptoms significantly improved during therapy with colchicine at a rate of 14.2%, 19%, 14.2%, 4.7% and 0% respectively (p < .05). No patients were discontinued on colchicine therapy because of adverse effects.
Colchicine stimulates the adenylate cyclase activity and increased the concentrations of both mucosal prostaglandin E2 and cAMP, which was more evident in jejunal mucosa (Rachmilewitz & Karmeli, 1980). As a result of the increase in the levels of mucosal prostaglandin E2 and cAMP, water accumulates in the lumen and induces diarrhea. The hypothesis was supported when nonsteroidal anti-inflammatory drugs or steroids were noted to inhibit the prostaglandin E2 synthesis and stop diarrhea (Rachmilewitz & Karmeli).
Our results are similar to those of previously mentioned trials in which colchicine was revealed as an effective drug in the treatment of functional constipation (Verne, Eaker, Davis, & Sninsky, 1997). We conclude colchicine 0.5 mg three times a day seems effective and safe in the treatment of chronic functional constipation. Colchicine improves the constipation effectively while it does not cause an increase in abdominal symptoms which were commonly seen during therapy with routine laxatives. We suggest larger, long-term, double-blind, multicenter studies are needed to confirm these results.
Murat Saruc, MD
Aysen Sertdemir, RN
Hakan Yuceyar, MD
References