Controlled clinical comparison of paroxetine and fluvoxamine considering the serotonin transporter promoter polymorphism

Abstract

The present study aimed to compare the effects of two currently used selective serotonin reuptake inhibitors (SSRIs) in Japan taking the individual background in 5-HTT gene-linked polymorphic region (5HTTLPR) genotype into account. Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression. Patients with the l allele had a greater percentage reduction on the total score (P=0.059) and somatic anxiety items (P=0.026) of the 21-item Hamilton Depression Rating Scale (HAM-D) score compared to s/s genotype carriers. Paroxetine was significantly more effective than fluvoxamine in the s/s carriers, as evaluated on the percentage reduction in total score (P=0.012) and core (P=0.049) HAM-D after 4 weeks of medication, but not in the l/s carriers. These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs, and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis.

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

“…Indeed some evidence suggest that the association between 5-HTTLPR and treatment response is due to acceleration, more than overall response rate. 24,32,46 The results of our study suggest the period of assessment could be an important factor to evaluate the response rate, while on the other hand the remission rate seemed less influenced by the period of assessment because our results showed no heterogeneity in all remission comparison. This could be due to the fact that remission was evaluated in a longer length of observation: only two studies within 4 weeks.…”

Pharmacogenetics of antidepressant response

“…[176][177][178][179][180] On the other hand, studies involving Asian populations usually report conflicting results: some studies reported that the short 5-HTTLPR allele was associated with better outcomes, [181][182][183][184] some found no effect of 5-HTTLPR genotype on treatment efficacy 121,185,186 and some reported that the long 5-HTTLPR allele was associated with better outcomes. 83,[187][188][189][190][191] Interestingly, Lotrich and colleagues 192 recently reported that paroxetine blood concentration was positively associated with HAM-D response in a sample of elderly patients, but this association was found to be significant only in carriers of the short allele. In contrast, when augmentation strategies have been investigated, the short allele has been associated with a better response in patients prescribed pindolol or lithium.…”

“…As a consequence, most of the published papers appear to be biased toward the items they considered poorly. Moreover, the question of phenotype resurfaces, as genetic variations have been shown to be more strictly associated with clusters of symptoms (e.g., somatic complaints) than with complex phenotypes (e.g., MDD), 187,189,353 which could also be responsible for the inconsistent findings in literature. A more strict control for endophenotypes may then be suggested.…”

Effects of the Serotonin Type 2A, 3A and 3B Receptor and the Serotonin Transporter Genes on Paroxetine and Fluvoxamine Efficacy and Adverse Drug Reactions in Depressed Japanese Patients

“…A functional polymorphism was identified in the upstream regulatory region of the serotonin transporter gene (SERTPR) [8] . In many studies, including one of our group [9] , the long variant of SERTPR has been associated with a good response to SSRIs [10][11][12][13][14] , although conflicting results have also been reported in Asian populations [15,16] . This discrepancy has not yet been addressed but may be due to the influence of other molecules, which might modulate serotonergic neurotransmission.…”