Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial.
BACKGROUND
Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).


OBJECTIVE
To test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants.


METHODS
In an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163).


RESULTS
Altogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI -2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype.


CONCLUSIONS
It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.
School of Social and Community Medicine, University of Bristol, UK. Glyn.lewis@bristol.ac.uk
Glyn
G
Lewis
Jean
J
Mulligan
Nicola
N
Wiles
Philip
P
Cowen
Nick
N
Craddock
Masashi
M
Ikeda
Detelina
D
Grozeva
Victoria
V
Mason
David
D
Nutt
Deborah
D
Sharp
Debbie
D
Tallon
Laura
L
Thomas
Michael C
MC
O'Donovan
Tim J
TJ
Peters
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D000077593:Reboxetine; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
D000928:Antidepressive Agents; D009025:Morpholines; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D000077593:Reboxetine