title: 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.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, Advanced Center for Interventions and Services Research in Late-Life Mood Disorders, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Alexandre Y
authors.initials: AY
authors.lastname: Dombrovski
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.forename: Jules I
authors.initials: JI
authors.lastname: Rosen
authors.forename: Meredith
authors.initials: M
authors.lastname: Wallace
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Houck
authors.forename: Sati
authors.initials: S
authors.lastname: Mazumdar
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001526:Behavioral Symptoms / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D015283:Citalopram / Q000009:adverse effects* / Q000627:therapeutic use; D003704:Dementia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D015283:Citalopram; D018967:Risperidone; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors