title: Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study.
abstract: Pharmacogenetic-based dosing support tools have been developed to personalize antidepressant-prescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants.
  
  
  
  To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission.
  
  
  
  A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n=119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission.
  
  
  
  Among remitters (n=95), there was a strong concordance (Kendall's τ-b=0.84, P=0.0001; Cohen's κ=0.82, P=0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool.
  
  
  
  Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing.
authors: Departments of aPsychiatry bGeneral Practice cFlorey Institute of Neuroscience and Mental Health, University of Melbourne dDepartment of Psychological Sciences, Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorne eMolecular Genetics, Healthscope Pathology fSchool of Medicine, IMPACT Strategic Research Centre, Deakin University, Geelong, Victoria, Australia gCentre for Addiction and Mental Health, Campbell Family Research Institute hDepartment of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors: Chad A
authors: CA
authors: Bousman
authors: Daniel J
authors: DJ
authors: Müller
authors: Chee H
authors: CH
authors: Ng
authors: Keith
authors: K
authors: Byron
authors: Michael
authors: M
authors: Berk
authors: Ajeet B
authors: AB
authors: Singh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D000069468:Desvenlafaxine Succinate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D000071184:Pharmacogenomic Variants; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000928:Antidepressive Agents; D000069468:Desvenlafaxine Succinate; D014453:Glucuronosyltransferase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000099148:UGT1A1 Enzyme; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1