Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action.

BACKGROUND The neuropharmacological actions of antidepressants are well characterised but our understanding of how these changes translate into improved mood are still emerging. AIMS To investigate whether actions of antidepressant drugs on emotional processing are a mediating factor in the effects of these drugs in depression. METHOD We examined key published findings that explored the effects of antidepressants on behavioural and functional magnetic resonance imaging (fMRI) measures of emotional processing. RESULTS Negative emotional bias has been reliably associated with depression. Converging results suggest that antidepressants modulate emotional processing and increase positive emotional processing much earlier than effects on mood. These changes in emotional processing are associated with neural modulation in limbic and prefrontal circuitry. CONCLUSIONS Antidepressants may work in a manner consistent with cognitive theories of depression. Antidepressants do not act as direct mood enhancers but rather change the relative balance of positive to negative emotional processing, providing a platform for subsequent cognitive and psychological reconsolidation.