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


Dombrovski, Alexandre Y., Mulsant, Benoit H., Ferrell, Robert E., Lotrich, Francis E., Rosen, Jules I., Wallace, Meredith, Houck, Patricia R., Mazumdar, Sati, Pollock, Bruce G.


International Clinical Psychopharmacology, Volume: 25, No.: 1, Pages.: 37-45

Year of Publication



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.;

Bibtex Citation

@article{Dombrovski_2010, doi = {10.1097/yic.0b013e328333ee10}, url = {}, year = 2010, month = {jan}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, volume = {25}, number = {1}, pages = {37--45}, author = {Alexandre Y. Dombrovski and Benoit H. Mulsant and Robert E. Ferrell and Francis E. Lotrich and Jules I. Rosen and Meredith Wallace and Patricia R. Houck and Sati Mazumdar and Bruce G. Pollock}, title = {Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms}, journal = {International Clinical Psychopharmacology} }


adverse effects, aged, aged, 80 and over, alleles, and, antipsychotic agents, behavioral symptoms, citalopram, complications, dementia, drug, drug therapy, female, genetics, genotype, humans, male, polymorphism genetic, psychotic disorders, risperidone, serotonin plasma membrane transport proteins, serotonin uptake inhibitors, therapeutic use, tolerance, treatment outcome

Countries of Study


Types of Dementia

Dementia (general / unspecified)

Types of Study

Randomised Controlled Trial

Type of Outcomes



Hospital Inpatient Care

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Antipsychotics and antidepressants