POLYMORPHISM WITHIN THE PROMOTER OF THE SEROTONIN TRANSPORTER GENE AND ANTIDEPRESSANT EFFICACY OF FLUVOXAMINE

Depression with psychotic features has been shown to respond to select ive serotonin reuptake inhibitors (SSRIs), The serotonin transporter ( 5-HTT) is a prime target for SSRIs, A functional polymorphism within t he promoter region of the 5-HTT gene, leading to different transcripti onal efficiency, was recently reported, We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antide pressant response to fluvoxamine and/or augmentation with pindolol (a serotonin autoreceptors antagonist) which has been suggested as an aug mentation therapy for nonresponders, One hundred and two inpatients wi th major depression with psychotic features were randomly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindo lol for 6 weeks. Depression severity was assessed once a week using th e Hamilton Depression Rating Scale. Allelic variation in each subject was determined using a PCR-based method. Data were analyzed with a thr ee-way repeated measures analysis of variance, Both homozygotes for th e long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) sho wed a better response to fluvoxamine than homozygotes for the short va riant (s/s), In the group treated with fluvoxamine plus pindolol all t he genotypes acted like l/l treated with fluvoxamine alone. Fluvoxamin e efficacy in delusional depression seems to be related to allelic var iation within the promoter of the 5-HTT gene. Even though other factor s may be implicated, genotyping at 5-HTT promoter may represent a prom ising tool to individualize the pharmacological treatment of depressio n.