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Genetic polymorphisms in the treatment of depression: Speculations from an augmentation study using atomoxetine
- Source :
-
Psychiatry Research . Jan2010, Vol. 175 Issue 1/2, p67-73. 7p. - Publication Year :
- 2010
-
Abstract
- Abstract: Treatment-resistant depression may be related to polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) or dysregulation of noradrenergic systems. To examine 5-HTTLPR genotypes and responses to treatment, adult patients (N =261) with current major depression and a symptom severity rating ≥18 on the 17-item Hamilton Depression Rating Scale (HAMD17) were treated for 8 weeks with open-label sertraline (100–200 mg/d). Patients remaining symptomatic (total score >4, or >1 on any item of the HAMD17 Maier–Philipp subscale) were randomly assigned to double-blind therapy with sertraline plus either atomoxetine (40–120 mg/d) or placebo for 8 additional weeks. 5-HTTLPR genotype did not predict responses to sertraline monotherapy or discontinuation rates. Among the 138 patients remaining symptomatic after sertraline monotherapy (L/L=21%, S/L=50%, S/S=29%), significantly more S/S-genotype patients achieved remission under combined sertraline/atomoxetine treatment relative to the other genotypes (S/S=81.8%; non-S/S=32.7%), but not under sertraline/placebo treatment (S/S=35.7%; non-S/S=37.7%). Minor genotypic differences were noted in adverse event profiles. In patients with poor responses to sertraline monotherapy for depression, addition of atomoxetine may improve responses to treatment of depression in S/S-genotyped patients. Although this study is speculative, it represents a pharmacologically and genotypically well-defined patient population. Clinical Trials Registry #: NCT00485862. URL where available: http://www.clinicaltrials.gov/ct/show/NCT00485862?order=1. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 01651781
- Volume :
- 175
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- Psychiatry Research
- Publication Type :
- Academic Journal
- Accession number :
- 47055700
- Full Text :
- https://doi.org/10.1016/j.psychres.2009.01.005