Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine.
Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors (SSRIs). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was recently reported. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and/or augmentation with pindolol (a serotonin autoreceptors antagonist) which has been suggested as an augmentation therapy for nonresponders. One hundred and two inpatients with major depression with psychotic features were randomly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks. Depression severity was assessed once a week using the Hamilton Depression Rating Scale. Allelic variation in each subject was determined using a PCR-based method. Data were analyzed with a three-way repeated measures analysis of variance. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to fluvoxamine than homozygotes for the short variant (s/s). In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone. Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene. Even though other factors may be implicated, genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression.
Smeraldi
E
E
Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, and Università di Milano, School of Medicine, Italy.
Zanardi
R
R
Benedetti
F
F
Di Bella
D
D
Perez
J
J
Catalano
M
M
D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010869:Pindolol / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D010869:Pindolol; D016666:Fluvoxamine