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RATIONALE: Single-dose administration of selective serotonin and noradrenaline reuptake blockers has been shown to alter emotional processing in both behavioral and fMRI studies in healthy volunteers. Mirtazapine is a clinically established antidepressant with different pharmacological actions from monoamine reuptake inhibitors, involving blockade of noradrenaline α(2)-adrenoceptors and multiple 5-HT receptor subtypes. The aim of this study was to investigate the effect of a single dose of mirtazapine on the neural processing of emotional faces in healthy volunteers. METHODS: Twenty-eight participants were randomized to receive either a single dose of mirtazapine (15 mg) or placebo. Two hours later, participants underwent an fMRI scan, in which they classified fearful and happy faces on the basis of gender. Mood and subjective experience were also measured. RESULTS: Whole-brain analysis showed significant group × emotion interactions in a right amygdala-hippocampal region and left fronto-striatal cortex. Post hoc analyses revealed significantly reduced activation to fear and greater activation to happy faces in both regions under mirtazapine. CONCLUSIONS: Our findings indicate that a single dose of mirtazapine modulates neural activity to affective stimuli. Mirtazapine was found to decrease neural responses to fear and increase responses to happy facial expressions in regions implicated in the processing of emotional faces. These effects may be important for our understanding of the neural mechanisms of antidepressant action in anxiety and depression.

Original publication




Journal article


Psychopharmacology (Berl)

Publication Date





625 - 634


Adolescent, Adrenergic alpha-2 Receptor Antagonists, Adult, Affect, Analysis of Variance, Antidepressive Agents, Tricyclic, Brain Mapping, Double-Blind Method, England, Expressed Emotion, Facial Expression, Fear, Female, Happiness, Humans, Magnetic Resonance Imaging, Male, Mianserin, Mirtazapine, Neural Pathways, Placebo Effect, Serotonin Antagonists, Young Adult