Evidence map›Paper›PMID 21105279›Full record

Trial reportJournal of clinical psychopharmacology2010

Relation of serotonin transporter genetic variation to efficacy of escitalopram for generalized anxiety disorder in older adults.

Eric J Lenze, Alison M Goate, Petra Nowotny, David Dixon, Peichang Shi, Robert R Bies, Francis K Lotrich, Bruce L Rollman, M Katherine Shear, Paul A Thompson and 2 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of clinical psychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Genetics of generalized anxiety disorder and related traits.Dialogues in clinical neuroscience · 2017
    Review
  4. Article
  5. Review
  6. Anxiety disorders: new developments in old age.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2011
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Eric J LenzeDepartment of Psychiatry, Washington University School of Medicine, 660 S Euclid, Box 8134, St Louis, MO 63110, USA. lenzee@wustl.edu
Alison M Goate
Petra Nowotny
David Dixon
Peichang Shi
Robert R Bies
Francis K Lotrich
Bruce L Rollman
M Katherine Shear
Paul A Thompson
Carmen Andreescu
Bruce G Pollock

Funding

OPERATIONS CORE (285-351)P30MH068579 · NIMH · WASHINGTON UNIVERSITY · PI MCMILLEN, J. CURTIS · 2004 to 2008
$7.0M
Research Network Development Core (pages 329-374)P30MH071944 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REYNOLDS, CHARLES F. · 2005 to 2009
$6.7M
Risk Genes for Late-Life Depression after Hip FractureR01MH074596 · NIMH · WASHINGTON UNIVERSITY · PI LENZE, ERIC J · 2007 to 2011
$1.9M
Pharmacotherapy of Latelife Generalized Anxiety DisorderR01MH070547 · NIMH · WASHINGTON UNIVERSITY · PI LENZE, ERIC J · 2005 to 2009
$1.3M
NIMH NIH HHS P30 MH068579NIMH NIH HHS P30 MH071944NIMH NIH HHS P30 MH71944NIMH NIH HHS R01 MH070547NIMH NIH HHS R01 MH074596
6 · The paper itself

Abstract

objectiveGeneralized anxiety disorder (GAD) is common in older adults and can be treated with selective serotonin reuptake inhibitors (SSRIs). Genetic variation in the serotonin transporter gene promoter region is posited to be associated with SSRI efficacy: 2 polymorphisms (5-HTTLPR S/L and rs25531 g/a) form a haplotype with the La combination having higher transcription activity than other haplotypes. We hypothesized that GAD patients with no La haplotypes (La⁻) have lower SSRI treatment efficacy than those with 1 to 2 La haplotypes (La+).

methodThe study enrolled subjects aged 60 years or older with a principal diagnosis of GAD into a 12-week, randomized trial of escitalopram versus placebo. One hundred fifty subjects were genotyped for the serotonin transporter promoter region haplotype and were divided into La⁻ and La+ genotype groups; the primary analyses were done in European Americans only (n = 125; n = 59 with escitalopram and n = 66 with placebo).

resultsEscitalopram had no efficacy in the La⁻ group versus moderate efficacy in the La+ group. This genetic moderation of SSRI efficacy was due to a higher placebo response in La⁻ subjects, compared with La+ subjects. Drug concentration did not affect the genetic results. Exploratory analyses suggest that La⁻ subjects had greater variability of anxiety symptoms unrelated to treatment.

conclusionsThe serotonin transporter promoter haplotype is associated with variability in SSRI efficacy for late-life GAD. The variability may result from a genetic effect on anxiety symptom variability unrelated to treatment, rather than a pharmacodynamic effect that has been previously assumed. Further research is needed to understand the pharmacogenetic mechanism of this haplotype.

Indexed as

AgedAged, 80 and overAge FactorsAnxiety DisordersCitalopramFemaleGenotypeHaplotypesHumansMaleMiddle AgedPolymorphism, GeneticSelective Serotonin Reuptake InhibitorsSerotonin Plasma Membrane Transport ProteinsTreatment OutcomeCitalopramSelective Serotonin Reuptake InhibitorsSerotonin Plasma Membrane Transport Proteins

Identifiers

PMID21105279
PMCPMC3059101

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.