Pharmacogenomic Testing Reduced Prescribing of Medications with Predicted Drug-Gene Interaction among Veterans with Depression
Pharmacogenomic (PGx) testing is receiving increased attention as a mechanism to personalize medication selection. In theory, PGx testing may improve drug selection or dosing in patients with genetic variation that alters pharmacokinetics (what the body does to the drug) or pharmacodynamics (what the drug does to the body). PGx testing may be particularly helpful in the treatment of major depressive disorder (MDD) where initial treatment response can be expected in only 28-33% of patients. The Precision Medicine in Mental Health Care (PRIME Care) randomized clinical trial was designed to evaluate clinical outcomes related to PGx testing in routine clinical practice. Investigators compared treatment for MDD guided by PGx testing to usual care. Conducted at 22 VA medical centers between 2017 and 2021, the trial included 1,944 Veterans with a diagnosis of MDD, along with 676 frontline mental health and primary care clinicians. Results from a PGx test were given to clinicians in the pharmacogenomic-guided group (n=966), with the comparison group receiving usual care and access to PGx results after 24 weeks (n=978). Outcomes were assessed by blinded raters at 4, 8, 12, 18, and 24 weeks, and included the proportion of prescriptions with a predicted drug-gene interaction as well as any reduction in symptom severity.
- Among Veterans with MDD, the provision of PGx testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care.
- The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59%, 30%, and 11% compared to 26%, 55%, and 20% in the usual care group.
- Remission of symptoms reached a maximum difference of 17% among the PGx group vs 11% in the usual care group at 12 weeks – but was not significantly different at 24 weeks. There were no identified harms to patients related to the intervention.
- There was no attempt to blind either the clinician or patient in the study. Thus, the modest effects in the pharmacogenomic-guided group could be a placebo type effect.
- The trial used a proprietary pharmacogenomic test; therefore, results may not translate to other commercial products.
This study was funded by HSR&D (SDR 16-348). Dr. Oslin is the Director, and several authors are part of the VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC). Dr. Oslin is also part of HSR&D’s Center for Health Equity, Research and Promotion (CHERP).
Oslin D, Lynch K, Shih M-C, et al., and the PRIME Care Research Group. 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. JAMA. July 12, 2022;328(2):151-16.