title: Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study.
abstract: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non-response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting.
  
  
  
  We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations.
  
  
  
  One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n=93, 67.4%), followed by antipsychotics (n=28, 20.3%), benzodiazepines and hypnotics (n=13, 9.4%), and psychostimulants (n=4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n=68, 49.3%) or non-response (n=46, 33.3%). Inter-rate reliability of the scoring system between the pharmacologists was excellent (kappa=0.94). The probability of an association between ADR, TDM or non-response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non-response and ADR respectively.
  
  
  
  When indicated by clinical pharmacologists, ADR, TDM or non-response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland; INSERM UMR-S1144, Paris, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Lloret-Linares
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Victoria
authors.initials: V
authors.lastname: Rollason
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Kuntheavy Ing
authors.initials: KI
authors.lastname: Lorenzini
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Samer
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Daali
authors.affiliation: Division of Psychiatric Specialties, Department of Psychiatry and Mental Health, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gex-Fabry
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Aubry
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland. Electronic address: marie.besson@hcuge.ch.
authors.forename: Marie
authors.initials: M
authors.lastname: Besson
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions; D005838:Genotype; D006801:Humans; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003577:Cytochrome P-450 Enzyme System
keywords: Adverse drug reaction; Citalopram; Cytochrome P450; Duloxetine; Fluoxetine; Paroxetine; Personalized medicine; Psychotropic drugs; Risperidone; Venlafaxine