title: Prediction of early weight gain during psychotropic treatment using a combinatorial model with clinical and genetic markers.
abstract: BACKGROUND
  Psychotropic drugs can induce significant (>5%) weight gain (WG) already after 1 month of treatment, which is a good predictor for major WG at 3 and 12 months. The large interindividual variability of drug-induced WG can be explained in part by genetic and clinical factors.
  
  
  OBJECTIVE
  The aim of this study was to determine whether extensive analysis of genes, in addition to clinical factors, can improve prediction of patients at risk for more than 5% WG at 1 month of treatment.
  
  
  METHODS
  Data were obtained from a 1-year naturalistic longitudinal study, with weight monitoring during weight-inducing psychotropic treatment. A total of 248 Caucasian psychiatric patients, with at least baseline and 1-month weight measures, and with compliance ascertained were included. Results were tested for replication in a second cohort including 32 patients.
  
  
  RESULTS
  Age and baseline BMI were associated significantly with strong WG. The area under the curve (AUC) of the final model including genetic (18 genes) and clinical variables was significantly greater than that of the model including clinical variables only (AUCfinal: 0.92, AUCclinical: 0.75, P<0.0001). Predicted accuracy increased by 17% with genetic markers (Accuracyfinal: 87%), indicating that six patients must be genotyped to avoid one misclassified patient. The validity of the final model was confirmed in a replication cohort. Patients predicted before treatment as having more than 5% WG after 1 month of treatment had 4.4% more WG over 1 year than patients predicted to have up to 5% WG (P≤0.0001).
  
  
  CONCLUSIONS
  These results may help to implement genetic testing before starting psychotropic drug treatment to identify patients at risk of important WG.
authors.affiliation: aUnit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Centre for Psychiatric Neuroscience bDepartment of Psychiatry, Center for Psychiatric Epidemiology and Psychopathology cDepartment of Psychiatry, Service of Old Age Psychiatry dDepartment of Psychiatry, Service of General Psychiatry, Lausanne University Hospital, Hospital of Cery, Prilly eDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Frederik
authors.initials: F
authors.lastname: Vandenberghe
authors.forename: Núria
authors.initials: N
authors.lastname: Saigí-Morgui
authors.forename: Aurélie
authors.initials: A
authors.lastname: Delacrétaz
authors.forename: Lina
authors.initials: L
authors.lastname: Quteineh
authors.forename: Séverine
authors.initials: S
authors.lastname: Crettol
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ansermot
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gholam-Rezaee
authors.forename: Armin
authors.initials: A
authors.lastname: von Gunten
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011619:Psychotropic Drugs / Q000009:adverse effects*; D015430:Weight Gain
chemical_list: D005819:Genetic Markers; D011619:Psychotropic Drugs