Does the 5-HT1A rs6295 polymorphism influence the safety and efficacy of citalopram therapy in the oldest old?

Scutt, Greg, Overall, Andrew, Scott, Railton, Patel, Bhavik, Hachoumi, Lamia, Yeoman, Mark and Wright, Juliet (2018) Does the 5-HT1A rs6295 polymorphism influence the safety and efficacy of citalopram therapy in the oldest old? Therapeutic Advances in Drug Safety, 9 (7). pp. 355-366. ISSN 2042-0986

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Major depressive disorder (MDD) in older people is a relatively common, yet hard to treat problem. In this study, we aimed to establish if a single nucleotide polymorphism in the 5-HT1A receptor gene (rs6295) determines antidepressant response in patients aged > 80 years (the oldest old) with MDD.

Nineteen patients aged at least 80 years with a new diagnosis of MDD were monitored for response to citalopram 20 mg daily over 4 weeks and genotyped for the rs6295 allele.

Both a frequentist and Bayesian analysis was performed on the data. Bayesian analysis answered the clinically relevant question: ‘What is the probability that an older patient would enter remission after commencing selective serotonin reuptake inhibitor (SSRI) treatment, conditional on their rs6295 genotype?’

Individuals with a CC (cytosine–cytosine) genotype showed a significant improvement in their Geriatric Depression Score (p = 0.020) and cognition (p = 0.035) compared with other genotypes. From a Bayesian perspective, we updated reports of antidepressant efficacy in older people with our data and calculated that the 4-week relative risk of entering remission, given a CC genotype, is 1.9 [95% highest-density interval (HDI) 0.7–3.5], compared with 0.52 (95% HDI 0.1–1.0) for the CG (cytosine–guanine) genotype. The sample size of n = 19 is too small to draw any firm conclusions, however, the data suggest a trend indicative of a relationship between the rs6295 genotype and response to citalopram in older patients, which requires further investigation.

Item Type: Article
Keywords: ageing, Bayesian analysis, depression, pharmacogenomics
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Depositing User: Marie Shelton
Date Deposited: 10 Apr 2018 08:42
Last Modified: 01 Jul 2019 12:46

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