Serotonin transporter genotype interacts with paroxetine plasma levels to influence depression treatment response in geriatric patients.
OBJECTIVE
To investigate whether variable antidepressant response may be influenced by an interaction between the serotonin transporter promoter polymorphism (5-HTTLPR) and antidepressant concentration.


METHODS
Elderly subjects with depression treated with paroxetine (n = 110) were genotyped and assessed with the Hamilton Rating Scale for Depression (HAMD). A mixed-effect analysis of repeated measures was used.


RESULTS
There was an interaction between early paroxetine concentration and 5-HTTLPR genotype on symptomatic improvement over 12 weeks (F(18,59.5) = 1.8, p < 0.05), as well as main effects of both paroxetine concentration (F(68,55.3) = 2.4, p < 0.005) and genotype (F(2,74.2) = 5.7, p < 0.005). Paroxetine concentrations were correlated with change in HAMD scores after 2 weeks of treatment in subjects with the short (s) allele (r = 0.31, p < 0.05) but not in subjects homozygous for the long (l) allele.


CONCLUSIONS
The results demonstrate a concentration-response relation for paroxetine in late-life depression and support the hypothesis for both a direct main effect and a moderating influence of 5-HTTLPR alleles on this concentration-response relation.
Lotrich
Francis E
FE
NIMH Advanced Center in Interventions and Services Research for Late-Life Mood Disorders and the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. lotrichfe@upmc.edu
Pollock
Bruce G
BG
Kirshner
Margaret
M
Ferrell
Robert F
RF
Reynolds Iii
Charles F
CF
D000368:Aged; D000483:Alleles; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood* / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000627:therapeutic use*; D016896:Treatment Outcome
D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human