Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression

B G Pollock; R E Ferrell; B H Mulsant; S Mazumdar; M Miller; R A Sweet; S Davis; M A Kirshner; P R Houck; J A Stack; C F Reynolds; D J Kupfer

doi:10.1016/S0893-133X(00)00132-9

Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression

Neuropsychopharmacology. 2000 Nov;23(5):587-90. doi: 10.1016/S0893-133X(00)00132-9.

Authors

B G Pollock¹, R E Ferrell, B H Mulsant, S Mazumdar, M Miller, R A Sweet, S Davis, M A Kirshner, P R Houck, J A Stack, C F Reynolds, D J Kupfer

Affiliation

¹ Intervention Research Center for Late-Life Mood Disorders and the Geriatric Psychopharmacology Program, Graduate School of Public Health, Pittsburgh, PA 15213, USA.

PMID: 11027924
DOI: 10.1016/S0893-133X(00)00132-9

Abstract

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.

Publication types

Clinical Trial
Randomized Controlled Trial
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adrenergic alpha-Agonists / pharmacology
Aged
Alleles
Antidepressive Agents, Tricyclic / therapeutic use
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Depressive Disorder / drug therapy*
Depressive Disorder / genetics*
Depressive Disorder / psychology
Double-Blind Method
Female
Genotype
Humans
Lymphocytes / drug effects
Lymphocytes / metabolism
Male
Membrane Glycoproteins / genetics*
Membrane Glycoproteins / metabolism
Membrane Transport Proteins*
Middle Aged
Nerve Tissue Proteins*
Norepinephrine / pharmacology
Nortriptyline / therapeutic use
Paroxetine / therapeutic use*
Polymorphism, Genetic / genetics
Promoter Regions, Genetic
Psychiatric Status Rating Scales
Selective Serotonin Reuptake Inhibitors / therapeutic use*
Serotonin Plasma Membrane Transport Proteins

Substances

Adrenergic alpha-Agonists
Antidepressive Agents, Tricyclic
Carrier Proteins
Membrane Glycoproteins
Membrane Transport Proteins
Nerve Tissue Proteins
SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Paroxetine
Nortriptyline
Norepinephrine

Grants and funding

etc