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Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.

ABSTRACT: The risk/benefit ratio of pharmacotherapy for behavioral symptoms of dementia is questionable: second-generation antipsychotics are poorly tolerated, and the efficacy of alternative treatments, for example, 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 nondepressed patients with dementia hospitalized for behavioral or psychotic symptoms. Genotypes including the A/G polymorphism of the L allele (rs25531) were determined in 92 of 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 remained unchanged 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. In conclusion, 5-HTTLPR may be a useful biomarker of SSRI intolerance in dementia. Our findings of intolerance of a second-generation antipsychotics and persistence of psychosis in patients with low-expression alleles needs to be replicated.

SUBMITTER: Dombrovski AY

PROVIDER: S-EPMC2887732 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.

Dombrovski Alexandre Y AY Mulsant Benoit H BH Ferrell Robert E RE Lotrich Francis E FE Rosen Jules I JI Wallace Meredith M Houck Patricia R PR Mazumdar Sati S Pollock Bruce G BG

International clinical psychopharmacology 20100101 1

The risk/benefit ratio of pharmacotherapy for behavioral symptoms of dementia is questionable: second-generation antipsychotics are poorly tolerated, and the efficacy of alternative treatments, for example, 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 ...[more]

PMID: 19996755

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Project description:BACKGROUND:The serotonin (5-HT) transporter-linked polymorphic region (5-HTTLPR) moderates the relationship between stressful life events and depression. Given the high prevalence of depression in chronic pain, the primary aim of this preliminary study was to investigate the associations between the 5-HTTLPR and the severity of depressive symptoms in a cohort of adults with chronic pain. METHODS:Adults with chronic pain who were consecutively admitted to an outpatient pain rehabilitation program and met inclusion criteria were recruited for study participation (n=277). Individuals were genotyped for the 5-HTTLPR (including rs25531) and categorized as high, intermediate, or low expressors of the 5-HT transporter. The severity of depressive symptoms at admission was measured by using the Center for Epidemiologic Depression scale (CES-D). RESULTS:The distribution of the high-, intermediate-, and low-expressing genotypes was 61 (22%), 149 (54%), and 67 (24%), respectively. The Hardy-Weinberg P-value was 0.204, which indicated no departure from equilibrium. A main effect of 5-HTTLPR was observed for depressive symptoms (P=0.040) where Center for Epidemiologic Depression scale (CES-D) scores were significantly greater in the low-expressing group compared to the high- (P=0.019) and intermediate (P=0.029)-expressing groups. In multivariate multinomial logistic regression analysis adjusted for age, sex, pain severity, pain catastrophizing, and pain anxiety, greater CES-D scores were significantly associated with the 5-HTTLPR low-expressing group compared to the high-expressing group (P=0.023), but not for the low-expressing group compared to the intermediate-expressing group (P=0.056). CONCLUSION:These preliminary findings suggest that the triallelic 5-HTTLPR could influence the severity of depressive symptoms in adults with chronic pain. Individuals with chronic pain may be particularly vulnerable to the moderating effects of 5-HTTLPR due to high levels of pain-related stress that are inherently present in this population.

Dataset Information

Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.

Publications

Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms.

Similar Datasets

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