Patients with major depressive disorder (MDD) often face prolonged periods before achieving remission or a noticeable treatment response due to the trial-and-error nature of prescribing effective medications. Pharmacogenomic testing, which tailors drug selection based on genetic profiles, has demonstrated improvements in remission and response rates, yet its long-term effects remain unclear. This study aimed to investigate whether pharmacogenomic-guided therapy enhances remission and response over time in MDD patients and whether these benefits are sustained. This research involved a prespecified post hoc analysis of the PRIME Care (Precision Medicine in Mental Healthcare) randomized clinical trial, a pragmatic study comparing pharmacogenomic-guided therapy with standard care among veterans diagnosed with depression. Participants were enrolled across 22 Department of Veterans Affairs medical centers by 676 clinicians and randomized to either the pharmacogenomic-guided treatment group or usual care. Multivariate Cox proportional hazards models were applied to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to assess the association between treatment approach and the first occurrence of response or remission as measured by the Patient Health Questionnaire-9 (PHQ-9). Of the 1,944 veterans in the PRIME Care trial, 1,764 (90.7%) had adequate follow-up data for analysis. Those receiving pharmacogenomic-guided therapy showed higher rates of remission (HR [95% CI] = 1.27 [1.05, 1.53]; p = 0.015) and response (HR [95% CI] = 1.21 [1.05, 1.40]; p = 0.010) compared to usual care. Analysis of Schoenfeld residuals revealed no significant changes in proportional hazards for remission (p = 0.931) or response (p = 0.112), indicating that the treatment benefit remained stable over the 24-week observation period. Use of pharmacogenomic-guided treatment led to quicker initial remission and response in patients with MDD, with these advantages persisting over six months and showing no evidence of diminishing over time.
