title: An observational study of clozapine induced sedation and its pharmacological management.
abstract: Clozapine induced sedation is common but its management is unclear. We analyzed the factors associated with clozapine-induced sedation and the efficacy of common pharmacological strategies. We conducted a naturalistic observational study using two years electronic records of a cohort patients and three analyses: a cross sectional analysis of factors associated with total number of hours slept (as an objective proxy of sedation), and two prospective analyses of which factors were associated with changes in hours slept and the efficacy of two pharmacological strategies. 133 patients were included, of which 64.7% slept at least 9h daily. Among monotherapy patients (n=30), only norclozapine levels (r=.367, p=.03) correlated with hours slept. Using the prospective cohort (n=107), 42 patients decreased the number of hours slept, due to decreasing clozapine (40%) or augmenting with aripiprazole (36%). These two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects respectively but the majority (81.8% and 73.9%) did not reduce number of hours slept. Thus, pharmacological and non-pharmacological factors are involved in sedation. Norclozapine plasma levels correlated with total sleeping hours. Reducing clozapine and aripiprazole augmentation were associated to amelioration of sedation, although both strategies were effective only in a limited numbers of subjects.
authors.affiliation: Institut de Neuropsiquiatria i Adiccions, Parc de Salut Mar and Fundacio IMIM, Barcelona, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Ramos Perdigués
authors.affiliation: Centre de Salut Mental Horta, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sauras Quecuti
authors.affiliation: Institut de Neuropsiquiatria i Adiccions, Parc de Salut Mar and Fundacio IMIM, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Mané
authors.affiliation: Cambridgeshire and Peterborough NHS Foundation Trust, UK.
authors.forename: Louisa
authors.initials: L
authors.lastname: Mann
authors.affiliation: Cambridgeshire and Peterborough NHS Foundation Trust, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Mundell
authors.affiliation: Cambridgeshire and Peterborough NHS Foundation Trust, UK; Department of Psychiatry, Behavioural and Clinical Neuroscience Institute (BCNI), University of Cambridge, UK; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain. Electronic address: ef280@cam.ac.uk.
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Egea
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D003024:Clozapine / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D011446:Prospective Studies; D012559:Schizophrenia / Q000188:drug therapy; D012890:Sleep / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D000068180:Aripiprazole; D003024:Clozapine
keywords: Clozapine; Drowsiness; Management; Schizophrenia; Sedation; Treatment