Acute Neural Effects of Selective Serotonin Reuptake Inhibitors versus Selective Noradrenaline Reuptake Inhibitors of Emotion Processing: Implications for Differential Treatment Efficacy

Citation: Outhred, T., Hawkshead, B. E., Wager, T. D., Das, P., Malhi, G. S., & Kemp, A. H. (2013). Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy. Neuroscience & Biobehavioral Reviews, 37(8), 1786-1800.

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Clinical research has demonstrated differential efficacy of selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which may relate to differential neural effects these medications have on emotional brain processes. Functional neuroimaging studies have examined the impact of either SSRIs or NRIs on emotion processing tasks, but their effects have not been directly contrasted. Here we present findings from a meta-analysis integrating and contrasting the findings from these disparate studies in order to examine whether SSRIs and NRIs have different effects on emotion processing. We employed Multi-Level Kernel Density Analysis, a whole-brain based quantitative meta-analysis technique on fMRI studies that have examined the effects of a single dose of an SSRI or NRI on the processing of emotional faces or pictures in healthy participants. Seven SSRI and four NRI studies were eligible for inclusion. Faces increased activity in the amygdala, while pictures increased dorsolateral prefrontal cortex, mid-cingulate cortex, and thalamus activation. SSRIs decreased amygdala responses, suggesting reduced emotional automaticity and reactivity to emotion stimuli, whereas NRIs increased activation in the dorsolateral prefrontal cortex, mid- and posterior cingulate cortex and thalamus, suggesting increased emotion regulation. As hypothesised, an interaction of antidepressant and task type was found, such that SSRIs modulated limbic and frontal activity during both the presentation of faces and pictures, whereas NRIs only modulated the activation in mid-brain and frontal regions during the presentation of pictures. Findings are interpreted within a novel model of the differential effects of SSRIs and NRIs on emotion processing.