Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.
Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.
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DOI：
10.1097/yic.0b013e328333ee10
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发表时间：
2010-01
影响因子：
2.6
通讯作者：
Pollock BG
中科院分区：
文献类型：
--
作者：
Dombrovski AY;Mulsant BH;Ferrell RE;Lotrich FE;Rosen JI;Wallace M;Houck PR;Mazumdar S;Pollock BG
The risk/benefit ratio of pharmacotherapy for behavioral symptoms of dementia is questionable: second-generation antipsychotics (SGAs) are poorly tolerated, and efficacy of alternative treatments, e.g. selective serotonin-reuptake inhibitors (SSRIs), is uncertain. Biomarkers of treatment response may improve this risk/benefit ratio. The length polymorphism of the serotonin transporter promoter gene (5-HTTLPR/SLC6A4) may moderate tolerability of SSRIs and expression of behavioral symptoms in dementia. We assessed the effect of 5-HTTLPR on tolerability and efficacy of citalopram and risperidone in a 12-week randomized controlled trial which included non-depressed patients with dementia hospitalized for behavioral or psychotic symptoms. Genotypes including the A/G polymorphism of the L allele (rs25531) were determined for 92/103 participants. We used pattern-mixture models to account for dropout. Low-expression alleles (S and Lg) predicted greater early and overall side effects of citalopram and early treatment discontinuation, These results held after excluding African-American participants and in covariate analyses. Unexpectedly, low-expression alleles seemed to predict greater early side effects of risperidone (but not early discontinuation) and poorer early response of psychosis symptoms to risperidone. 5-HTTLPR may be a useful biomarker of SSRI intolerance in dementia. Our findings of intolerance of an SGA and persistence of psychosis in patients with low-expression alleles needs to be replicated.
