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| Articles
by
A Placentino |
Total Records (
3 ) for
A Placentino |
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R Uher
,
N Perroud
,
M. Y. M Ng
,
J Hauser
,
N Henigsberg
,
W Maier
,
O Mors
,
A Placentino
,
M Rietschel
,
D Souery
,
T Zagar
,
P. M Czerski
,
B Jerman
,
E. R Larsen
,
T. G Schulze
,
A Zobel
,
S Cohen Woods
,
K Pirlo
,
A. W Butler
,
P Muglia
,
M. R Barnes
,
M Lathrop<
,
A Farmer
,
G Breen
,
K. J Aitchison
,
I Craig
,
C. M Lewis
and
P. McGuffin
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Objective
The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs.
Method
High-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial.
Results
Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline. Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene. A set of 72 a priori-selected candidate genes did not show pharmacogenetic associations above a chance level, but an association with response to escitalopram was detected in the interleukin-6 gene, which is a close homologue of IL11.
Conclusions
While limited statistical power means that a number of true associations may have been missed, these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates. Genome-wide studies, if properly replicated, may thus be important steps in the elucidation of the genetic basis of pharmacological response.
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P Huezo Diaz
,
R Uher
,
R Smith
,
M Rietschel
,
N Henigsberg
,
A Marusic
,
O Mors
,
W Maier
,
J Hauser
,
D Souery
,
A Placentino
,
A Zobel
,
E. R Larsen
,
P. M Czerski
,
B Gupta
,
F Hoda
,
N Perroud
,
A Farmer
,
I Craig
,
K. J Aitchison
and
P. McGuffin
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Background
There have been conflicting reports on whether the length polymorphism in
the promoter of the serotonin transporter gene (5-HTTLPR) moderates the
antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We
hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by
gender, age and other variants in the serotonin transporter gene.
Aims
To test the hypothesis that the 5-HTTLPR differently influences response to
escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake
inhibitor).
Method
The 5-HTTLPR and 13 additional markers across the serotonin transporter
gene were genotyped in 795 adults with moderate-to-severe depression treated
with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for
Depression (GENDEP) project.
Results
The 5-HTTLPR moderated the response to escitalopram, with long-allele
carriers improving more than short-allele homozygotes. A significant three-way
interaction between 5-HTTLPR, drug and gender indicated that the effect was
concentrated in males treated with escitalopram. The single-nucleotide
polymorphism rs2020933 also influenced outcome.
Conclusions
The effect of 5-HTTLPR on antidepressant response is SSRI specific
conditional on gender and modulated by another polymorphism at the 5'
end of the serotonin transporter gene. |
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R Uher
,
A Farmer
,
N Henigsberg
,
M Rietschel
,
O Mors
,
W Maier
,
D Kozel
,
J Hauser
,
D Souery
,
A Placentino
,
J Strohmaier
,
N Perroud
,
A Zobel
,
A Rajewska Rager
,
M. Z Dernovsek
,
E. R Larsen
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P Kalember
,
C Giovannini
,
M Barreto
,
P McGuffin
and
K. J. Aitchison
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Background
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.
Aims
To evaluate a simple self-report measure and describe adverse reactions to
antidepressants in a large sample.
Method
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.
Results
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.
Conclusions
Adverse reactions to antidepressants can be reliably assessed by
self-report. Attention to specific adverse reactions may improve adherence to
antidepressant treatment. |
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