Pharmacogenetics of venlafaxine response in older adults with depression and chronic lower back pain

BACKGROUND: Late-life depression (LLD) and chronic low back pain frequently co-occur and exacerbate one another. Outcomes with antidepressant treatment in this population are often suboptimal. Pharmacogenetic factors may help explain variability in antidepressant response. Building on prior findings suggesting that SLC6A2 variation predicts venlafaxine response in LLD, we examined whether such genetic associations extend to older adults with chronic low back pain in the ADAPT study (Addressing Depression and Pain Together). METHODS: Older adults with LLD and chronic low back pain received venlafaxine treatment over 20 weeks. The primary analysis focused on the SLC6A2 rs2242446 variant, whereas secondary analyses evaluated 37 variants across 14 candidate genes implicated in depression or pain. Outcomes included percentage improvement in PHQ-9 scores, remission, and time to remission. RESULTS: Genotype data were available for 101 participants. Primary analyses showed no association between SLC6A2 rs2242446 and any outcome measure. In secondary analyses, the serotonin 1A receptor gene (HTR1A) variant rs6295 emerged as the most consistent nominal genetic signal. CONCLUSION: Previously reported pharmacogenetic signal involving SLC6A2 did not extend to a more clinically complex population, whereas exploratory serotonergic variation showed a nominal association. Findings inform pharmacogenetic research in late-life depression with comorbid pain.Clinical trial registration identifier is NCT01124188.