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.


OBJECTIVE
To investigate whether actions of antidepressant drugs on emotional processing are a mediating factor in the effects of these drugs in depression.


METHODS
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.
Harmer
Catherine J
CJ
University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK. Catherine.harmer@psych.ox.ac.uk
Goodwin
Guy M
GM
Cowen
Philip J
PJ
D000339:Affect / Q000187:drug effects; D000928:Antidepressive Agents / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004644:Emotions / Q000187:drug effects*; D005149:Facial Expression; D006801:Humans; D008032:Limbic System / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008959:Models, Neurological; D008960:Models, Psychological; D009341:Negativism; D013997:Time Factors
D000928:Antidepressive Agents