Prevalence and Factors Associated with Clozapine-Related Constipation

Background Despite being a very effective treatment for resistant schizophrenia and bipolar disorder, use of clozapine is limited by adverse effects. Constipation is a common but potentially life-threatening adverse effect of clozapine that is understudied. The objective was to study the prevalence and factors associated with constipation in those receiving clozapine compared with control subjects. Methods Fifty patients in age group of 18 to 55 years receiving clozapine were compared with 50 patients in the same age group receiving medications other than clozapine. Presence of constipation was ascertained using the World Gastroenterology Organization Practice Guidelines definition. The severity of constipation was assessed using Constipation Assessment Scale and Bristol Stool Form Scale, and anticholinergic burden was assessed using Anticholinergic Burden Scale. Results Among clozapine-treated patients, 28 (56%) had constipation as compared with 11 (22%) in the control subjects (P < 0.001); the odds of developing constipation was 4.5 (95% confidence interval, 1.9-10.8). Kaplan-Meier survival analysis showed median time to onset of constipation in clozapine-treated patients was 60 days (SE, 13.1 days; 95% confidence interval, 34.3-85.7 days) and median dose of clozapine was 300 mg/d (interquartile range, 312 mg/d). Clozapine group had high Constipation Assessment Scale scores (P = 0.005, Cohen d = 1.17) and higher prevalence of types 1 and 2 Bristol stool types (Fisher exact P = 0.005, Cramer V = 0.59). Conclusions Constipation was prevalent in more than half of patients receiving clozapine, which was severe and took longer time for recovery. Limitations include using a hospital-based sample and that dietary habits and lifestyle factors were not studied.