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

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 >80years (the oldest old) with MDD. 35Nineteen patients ≥80 years-old, 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 SSRI treatment, conditional on their rs6295 genotype?’. Individuals with a CC genotype showed a significant improvement in their Geriatric Depression Score (p=0.020) and cognition (p=0.035) compared to 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% HDI 0.7-3.5), compared to 0.52 (95% HDI 0.1-1.0) for the CG 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.