BACKGROUND AND PURPOSE:

• Only approximately 30% of patients with major depressive disorder (MDD) respond to the first treatment
• Oslin et al. (JAMA, 2022) determined whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes

METHODS:

• Pragmatic, randomized clinical trial
  • The Precision Medicine in Mental Health Care (PRIME Care) Trial 
• Participants
  • Patients at Department of Veterans Affairs medical centers with MDD who were initiating or switching treatment with a single antidepressant
  • Exclusions: Active substance use disorder | Mania | Psychosis | Concurrent treatment with a specified list of medications
• Intervention
  • Clinicians given access to pharmacogenomic testing
  • Usual care with access to pharmacogenomic results revealed >24 weeks
• Study design
  • Remission was measured with the Patient Health Questionnaire–9 (PHQ-9; remission was defined as PHQ-9 ≤ 5)
  • Remission was analyzed as a repeated measure across 24 weeks by blinded raters
• Primary outcomes
  • The proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization
  • Remission of depressive symptoms

RESULTS:

• Pharmacogenomic-guided group: 966 patients | Usual care group: 978 patients
  • Mean age: 48 years | 25% women | 79% completed 24-week assessment
• Estimated risk of receiving antidepressants with
  • No drug-gene interactions
    • Pharmacogenomic-guided group: 59.3%
    • Usual care group: 25.7%
  • Moderate drug-gene interactions
    • Pharmacogenomic-guided group: 30.0%
    • Usual care group: 54.6%
  • Substantial drug-gene interactions
    • Pharmacogenomic-guided group: 10.7%
    • Usual care group: 19.7%
• The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction
  • No drug-gene vs moderate/substantial interaction
    • OR 4.32 (95% CI, 3.47 to 5.39); P<0 .001
  • No/moderate vs substantial interaction
    • OR 2.08 (95% CI, 1.52 to 2.84); P=0.005
  • P<0.001 for overall comparison
• Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care
  • OR 1.28 (95% CI, 1.05 to 1.57); P=0.02
  • Risk difference 2.8% (95% CI, 0.6 to 5.1)
• Remission rates at week 24 weeks were not significantly different
  • Pharmacogenomic-guided group: 17.2%  
  • Usual care: 16.0%
  • Estimated risk difference 1.5% (95% CI, −2.4% to 5.3); P=0.45

CONCLUSION:

• Compared to usual care, pharmacogenomic testing reduced that risk that patients with MDD would be prescribed an antidepressant that would have moderate or substantial drug-gene interactions
• Symptom remission was higher in patients who underwent pharmacogenomic testing, but this effect was small and nonpersistent
• The authors state

Overall, there were small positive effects on symptom remission over the 24 weeks with peak differences early in the trial and no significant difference in remission at 24 weeks

The negative consequences of pharmacogenomic testing are low and relate principally to cost

While the benefit on a population level may be limited, there may be value in the aggregate and to the individual patient

Learn More – Primary Sources:

Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial

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