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J Psychopharmacol. 2011 Jul;25(7):867-74. doi: 10.1177/0269881110376683. Epub 2010 Sep 8.

Variation in GNB3 predicts response and adverse reactions to antidepressants.

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MRC SGDP Centre, Institute of Psychiatry, King's College London, UK.


There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response.

[Indexed for MEDLINE]
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Br J Psychiatry. 2009 Sep;195(3):202-10. doi: 10.1192/bjp.bp.108.061960.

Adverse reactions to antidepressants.

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P080 SGDP, Institute of Psychiatry, King's College London, London SE5 8AF, UK.

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  • Br J Psychiatry. 2010 May;196(5):417.



Adverse drug reactions are important determinants of non-adherence to antidepressant treatment, but their assessment is complicated by overlap with depressive symptoms and lack of reliable self-report measures.


To evaluate a simple self-report measure and describe adverse reactions to antidepressants in a large sample.


The newly developed self-report Antidepressant Side-Effect Checklist and the psychiatrist-rated UKU Side Effect Rating Scale were repeatedly administered to 811 adult participants with depression in a part-randomised multicentre open-label study comparing escitalopram and nortriptyline.


There was good agreement between self-report and psychiatrists' ratings. Most complaints listed as adverse reactions in people with depression were more common when they were medication-free rather than during their treatment with antidepressants. Dry mouth (74%), constipation (33%) and weight gain (15%) were associated with nortriptyline treatment. Diarrhoea (9%), insomnia (36%) and yawning (16%) were more common during treatment with escitalopram. Problems with urination and drowsiness predicted discontinuation of nortriptyline. Diarrhoea and decreased appetite predicted discontinuation of escitalopram.


Adverse reactions to antidepressants can be reliably assessed by self-report. Attention to specific adverse reactions may improve adherence to antidepressant treatment.

[Indexed for MEDLINE]
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