Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression.
The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.
Pollock
B G
BG
Intervention Research Center for Late-Life Mood Disorders and the Geriatric Psychopharmacology Program, Graduate School of Public Health, Pittsburgh, PA 15213, USA.
Ferrell
R E
RE
Mulsant
B H
BH
Mazumdar
S
S
Miller
M
M
Sweet
R A
RA
Davis
S
S
Kirshner
M A
MA
Houck
P R
PR
Stack
J A
JA
Reynolds
C F
CF
Kupfer
D J
DJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000368:Aged; D000483:Alleles; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000494:pharmacology; D009661:Nortriptyline / Q000627:therapeutic use; D017374:Paroxetine / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D000316:Adrenergic alpha-Agonists; D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine; D009661:Nortriptyline; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human