orlistat and Constipation

Obesity in adolescents presents many challenges for the patient, family, and physician. The myriad problems involving the GI tract will be managed more effectively when the treating physician has an understanding of the presentations, pathophysiology, appropriate laboratory evaluation, and approaches to treatment for these complications. In addition to being familiar with the pharmacotherapeutic options available, having an approach to behavioral change, such as MI, can be an extremely useful tool.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Constipation; Contraceptives, Oral, Combined; Diabetes Mellitus, Type 2; Digestive System Diseases; Fecal Incontinence; Gallstones; Gastroesophageal Reflux; Humans; Hypoglycemic Agents; Lactones; Metformin; Non-alcoholic Fatty Liver Disease; Orlistat; Pancreatitis; Pediatric Obesity

Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Colon; Constipation; Cross-Sectional Studies; Diarrhea; Double-Blind Method; Finland; Humans; Incidence; Lactones; Laxatives; Obesity; Olanzapine; Orlistat; Overweight; Patient Dropouts; Prevalence; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Weight Loss

Endocannabinoids are a family of lipid mediators involved in the regulation of gastrointestinal (GI) motility. The expression, localization and function of their biosynthetic enzymes in the GI tract are not well understood. Here, we examined the expression, localization and function of the enzyme diacylglycerol lipase-α (DAGLα), which is involved in biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG).. Cannabinoid CB1 receptor-deficient, wild-type control and C3H/HeJ mice, a genetically constipated strain, were used. The distribution of DAGLα in the enteric nervous system was examined by immunohistochemistry. Effects of the DAGL inhibitors, orlistat and OMDM-188 on pharmacologically induced GI hypomotility were assessed by measuring intestinal contractility in vitro and whole gut transit or faecal output in vivo. Endocannabinoid levels were measured by mass spectrometry.. DAGLα was expressed throughout the GI tract. In the intestine, unlike DAGLβ, DAGLα immunoreactivity was prominently expressed in the enteric nervous system. In the myenteric plexus, it was colocalized with the vesicular acetylcholine transporter in cholinergic nerves. In normal mice, inhibiting DAGL reversed both pharmacologically reduced intestinal contractility and pharmacologically prolonged whole gut transit. Moreover, inhibiting DAGL normalized faecal output in constipated C3H/HeJ mice. In colons incubated with scopolamine, 2-AG was elevated while inhibiting DAGL normalized 2-AG levels.. DAGLα was expressed in the enteric nervous system of mice and its inhibition reversed slowed GI motility, intestinal contractility and constipation through 2-AG and CB1 receptor-mediated mechanisms. Our data suggest that DAGLα inhibitors may be promising candidates for the treatment of constipation.

Topics: Animals; Arachidonic Acids; Constipation; Endocannabinoids; Gastrointestinal Motility; Glycerides; Isoleucine; Lactones; Lipoprotein Lipase; Male; Mass Spectrometry; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Orlistat; Receptor, Cannabinoid, CB1; Scopolamine