The British Journal of Psychiatry (2009) 195: 102-108. doi: 10.1192/bjp.bp.108.051193
© 2009 The Royal College of Psychiatrists
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SPECIAL ARTICLE

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

Catherine J. Harmer, DPhil, Guy M. Goodwin, DPhil, FRCPsych and Philip J. Cowen, MD, FRCPsych

University Department of Psychiatry, Warneford Hospital, Oxford, UK

Correspondence: Catherine Harmer, Warneford Hospital, Oxford OX3 7JX, UK. Email: Catherine.harmer{at}psych.ox.ac.uk

Declaration of interest

G.M.G. and P.J.C. have been members of advisory boards of pharmaceutical companies marketing antidepressants. C.J.H. has acted as a paid consultant for Lundbeck and Merck Sharp & Dohme and is on the advisory board of P1vital.

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.


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