Trino Baptista1, Edgardo Carrizo2, Erika Fernandez2, Lisette Connell2, Mercedes Servigna3, Agner Parra2, Jesus Quintero2, Albis Pabón4, Ignacio Sandia4, Euderruh Uzcáteguid4, Ana Serrano4, Natacha Pirela5, Lisbeth Villarreal6. 1. Department of Physiology, Los Andes University Medical School, Av. Tulio Febres Cordero, Mérida 5101-A, Venezuela. Electronic address: trinbap@yahoo.com. 2. Clinical Investigation Institute "Dr. Américo Negrette", Zulia University Medical School, Maracaibo, Venezuela. 3. Center for the Attention of Schizophrenics and their Families (CATESFAM), Maracaibo, Venezuela. 4. Department of Psychiatry, Los Andes University Medical School, Mérida, Venezuela. 5. Department of Chemistry, Bioanalysis Section, Zulia University Medical School, Maracaibo, Venezuela. 6. Maracaibo University Hospital, Maracaibo, Venezuela.
Abstract
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.
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.
Authors: Domenico De Berardis; Gabriella Rapini; Luigi Olivieri; Domenico Di Nicola; Carmine Tomasetti; Alessandro Valchera; Michele Fornaro; Fabio Di Fabio; Giampaolo Perna; Marco Di Nicola; Gianluca Serafini; Alessandro Carano; Maurizio Pompili; Federica Vellante; Laura Orsolini; Giovanni Martinotti; Massimo Di Giannantonio Journal: Ther Adv Drug Saf Date: 2018-02-06
Authors: Susanna Every-Palmer; Pete M Ellis; Mike Nowitz; James Stanley; Eve Grant; Mark Huthwaite; Helen Dunn Journal: CNS Drugs Date: 2017-01 Impact factor: 5.749
Authors: Ayala Shirazi; Brendon Stubbs; Lucia Gomez; Susan Moore; Fiona Gaughran; Robert J Flanagan; James H MacCabe; John Lally Journal: Int J Mol Sci Date: 2016-06-02 Impact factor: 5.923
Authors: Susanna Every-Palmer; Roger G Lentle; Gordon Reynolds; Corrin Hulls; Paul Chambers; Helen Dunn; Pete M Ellis Journal: Front Pharmacol Date: 2017-04-24 Impact factor: 5.810
Authors: Susanna Every-Palmer; Mike Nowitz; James Stanley; Eve Grant; Mark Huthwaite; Helen Dunn; Pete M Ellis Journal: EBioMedicine Date: 2016-02-15 Impact factor: 8.143