Previous studies have indicated that
antidepressants that inhibit the
serotonin transporter reduces oxidative stress.
DNA and
RNA damage from oxidation is involved in aging and a range of age-related pathophysiological processes. Here, we studied the urinary excretion of markers of
DNA and
RNA damage from oxidation,
8-oxodG and
8-oxoGuo, respectively, in the NeuroPharm cohort of 100 drug-free patients with
unipolar depression and in 856 non-psychiatric community controls. Patients were subsequently treated for 8 weeks with
escitalopram in flexible doses of 5-20 mg; seven of these switched to
duloxetine by week 4, as allowed by the protocol. At week 8, 82 patients were followed up clinically and with measurements of 8-oxodG/8-oxoGuo. Contextual data were collected in patients, including markers of
cortisol excretion and low-grade
inflammation. The intervention was associated with a substantial reduction in both 8-oxodG/8-oxoGuo excretion (25% and 10%, respectively). The change was not significantly correlated to measures of clinical improvement. Both markers were strongly and negatively correlated to
cortisol, as measured by the area under the curve for the full-day salivary
cortisol excretion. Surprisingly, patients had similar levels of
8-oxodG excretion and lower levels of
8-oxoGuo excretion at baseline compared to the controls. We conclude that intervention with
serotonin reuptake inhibitors in
unipolar depression is associated with a reduction in systemic
DNA and
RNA damage from oxidation. To our knowledge, this to date the largest intervention study to characterize this phenomenon, and the first to include a marker of
RNA oxidation.