Escitalopram but not placebo modulates brain rhythmic oscillatory activity in the first week of treatment of Major Depressive Disorder

Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5-8 Hz) and the alpha (8-12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms. Prefrontal delta-theta and alpha power were calculated for 194 subjects with moderate MDD prior to and one week after start of treatment. Changes at one week in delta-theta and alpha power, as well as the delta-theta/alpha ratio, were examined in three cohorts: initial (N = 70) and replication (N = 76) cohorts treated with escitalopram, and a cohort treated with placebo (N = 48). Mean delta-theta power significantly increased and alpha power decreased after one week of escitalopram treatment, but did not significantly change with placebo treatment. The delta-theta/alpha ratio change was a specific predictor of the likelihood of remission after seven weeks of medication treatment: a large increase in this ratio was associated with non-remission in escitalopram-treated subjects, but not placebo-treated subjects. Escitalopram and placebo treatment have differential effects on delta-theta and alpha frequency oscillations. Early increase in delta-theta/alpha may constitute a replicable biomarker for non-remission during SSRI treatment of MDD.