Escitalopram Treatment Improves Self-Referential Processing in Depression

boy about to take pills
boy about to take pills
Treatment with escitalopram potentiates positive self-processing, which may lead to normalization of increased and negatively biased self-focus.

According to a study recently published in the Journal of Affective Disorders, short-term escitalopram treatment decreased self-focus and negative self-concept in patients with major depressive disorder. Additionally, escitalopram’s direct effect on self-referential processing, which preceded any effect on depressive symptoms, exposed different factors at play in the mechanism of action of antidepressants.

The double-blind, randomized, placebo-controlled study included 32 patients diagnosed with major depressive disorder according to criteria established by the DSM-IV who had received no antidepressant therapy for at least 4 months prior to starting the study. Participants were randomly assigned to a group receiving placebo or a group receiving 10 mg of escitalopram for 1 week. Magnetic resonance imaging was used to measure the neural response to positive and negative self-referential adjectives, as well as to neutral adjectives, that were assessed daily in a questionnaire adapted from Russel’s circumplex model of affect. Healthy volunteers were matched to the placebo and escitalopram groups to serve as a study control.

Escitalopram decreased the neural response to self-referential words relative to the neutral control stimuli, and it increased the neural response to positive words relative to negative words. The placebo group showed decreased neural response to positive self-referential words relative to the healthy control group. The most interesting finding of the study was that changes in neural response from escitalopram were observed before any effects on depressive symptoms were noted.

The opposite effect of escitalopram on placebo and esitalopram groups (both with major depressive disorder), along with the direct effect of escitalopram on changes in neural response, reveal different influences in the mechanism of action of antidepressants on self-referential processing. The escitalopram group did not see any improvement in depressive systems in the study’s short timeframe; however, neural responses in this group were normalized in comparison with the unmedicated, healthy control group.

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Limitations of the study include a sample of mostly university students, hampering the generalizability of the study outcome on an older, less educated population. Differences in self-reported depression symptoms may have affected the results.

Researchers conclude “[escitalopram] seems to improve the regulation of self-referential processing, shifting attention from the internal to the external milieu. It also seems to specifically potentiate positive self-processing, possibly leading to normalization of increased and negatively biased self-focus. This finding contributes to the understanding of the mechanism of action of antidepressants.”


Komulainen E, Heikkilä R, Nummenmaa L, et al. Short-term escitalopram treatment normalizes aberrant self-referential processing in major depressive disorder.. J Affect Disord. 2018; 236:222-229.