title: Use of very-high-dose olanzapine in treatment-resistant schizophrenia.
abstract: Schizophrenia is a chronic illness with a progressive course that can be marked by resistance to antipsychotic treatment. This can make therapeutic support challenging for the practitioner, with results that are partial and unsatisfactory. In the literature, treatment with high-dose olanzapine (>20mg/day) appears to be a good alternative to clozapine, the gold standard for treatment-resistant schizophrenia. In the present observational prospective study, we studied the clinical and biological profiles of patients treated with olanzapine doses up to 100mg/day. In total, 50 patients were clinically and biologically assessed. We found a linear relationship between oral dose and serum concentration (Pearson's r=0.83, p<0.001) with effects of tobacco (p<0.05) and of coffee and tea consumption (p<0.01). Tolerance seemed to be good regardless of dose. No link was found between concentration and efficiency. Despite a nonexhaustive assessment of pharmacokinetic parameters, not least pharmacogenetic data (e.g., genotyping of cytochrome P450-1A2 or glycoprotein P Abcb1a), pharmacokinetic aspects alone cannot account for why the disease may sometimes be resistant to 20mg of olanzapine but respond to higher doses. A nuclear imaging study exploring brain occupancy by high-dose olanzapine, coupled with the abovementioned pharmacokinetic assessment, may prove a relevant experimental paradigm for studying the pathophysiological mechanisms of resistant schizophrenia.
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France; EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, France. Electronic address: jeanmariebatail@gmail.com.
authors.forename: J-M
authors.initials: JM
authors.lastname: Batail
authors.affiliation: Pharmacy Department, Centre Hospitalier Guillaume Régnier, Rennes, France; Laboratory of Experimental and Clinical Pharmacology, Rennes 1 University, Faculty of Medicine, Rennes, France; Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France.
authors.forename: B
authors.initials: B
authors.lastname: Langrée
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France; EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, France.
authors.forename: G
authors.initials: G
authors.lastname: Robert
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France; EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, France.
authors.forename: S
authors.initials: S
authors.lastname: Bleher
authors.affiliation: Rennes University Hospital, Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes, France; Laboratory of Experimental and Clinical Pharmacology, Rennes 1 University, Faculty of Medicine, Rennes, France; Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France.
authors.forename: M-C
authors.initials: MC
authors.lastname: Verdier
authors.affiliation: Rennes University Hospital, Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes, France; Laboratory of Experimental and Clinical Pharmacology, Rennes 1 University, Faculty of Medicine, Rennes, France; Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France.
authors.forename: E
authors.initials: E
authors.lastname: Bellissant
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France; EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, France.
authors.forename: B
authors.initials: B
authors.lastname: Millet
authors.affiliation: Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France; EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, France.
authors.forename: D
authors.initials: D
authors.lastname: Drapier
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011618:Psychotic Disorders / Q000188:drug therapy*; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: High dose; Olanzapine; Schizophrenia; Therapeutic drug monitoring; Therapeutic resistance