Colonic Transit Diagnostic Test Shows Significant Gastrointestinal Hypomotility in Clozapine-treated Patients in Comparison with Subjects Treated with Other Antipsychotics

Background: Constipation occurs in 25-60% of the subjects during administration of the antipsychotic drug (AP) clozapine (CLZ).

Methods: We used a colonic transit diagnostic test that quantifies in a single abdominal X-ray the number of silver O-ring markers out of 25 units ingested five days before. The quantity of markers is directly proportional to the degree of gastrointestinal hypomotility, and elimination of over 80% of the markers is considered normal. The test was applied to three groups of AP-treated subjects for at least three consecutive months: CLZ alone (n=45), CLZ+Other APs (n=28), and Other APs (n=64).

Results: The number of remaining markers at day 5 (mean±S.D.) was significantly higher in the CLZ alone (10.8±10.6) and in the CLZ+Other APs (9.7±9.7) groups than in the Other AP group (4.5±6.7), Kruskal-Wallis test: p=0.004. No significant associations were found between the number of markers, age, AP dose and treatment duration. All subjects who passed <80% of markers - which approximately corresponds to the 60th percentile of marker elimination - showed a scattered marker distribution along the colon, thus suggesting colon inertia. In subjects with hypomotility, 38.5% of the CLZ group, 25% of the CLZ+Other APs group, and 25% of the Other APs group were negative for the Rome III clinical criteria of constipation, thus showing objective, not subjective, hypomotility.

Conclusions: This study objectively confirms significant gastrointestinal hypomotility associated with CLZ administration.