Concordance between actual and pharmacogenetic predicted desvenlafaxine dose needed to achieve remission in major depressive disorder: a 10-week open-label study

Pharmacogenet Genomics. 2017 Jan;27(1):1-6. doi: 10.1097/FPC.0000000000000253.

Abstract

Background: 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.

Objective: To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission.

Materials and methods: 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.

Results: 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.

Conclusion: Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Adult
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / pharmacokinetics
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics
  • Desvenlafaxine Succinate / administration & dosage*
  • Desvenlafaxine Succinate / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Humans
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Pharmacogenomic Variants
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Treatment Outcome
  • White People / genetics

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antidepressive Agents
  • Multidrug Resistance-Associated Proteins
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • multidrug resistance-associated protein 1
  • Desvenlafaxine Succinate