Does the 5-HT_1A rs6295 polymorphism influence the safety and efficacy of citalopram therapy in the oldest old?

Abstract

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-HT 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 ( = 0.020) and cognition ( = 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 = 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.

Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm

“…22 In small studies of the elderly, the C allele was protective against depressed mood in healthy athletes compared to nonathletes (n = 55 v. 58) 84 and enhanced remission to 4-week citalopram treatment in people recently diagnosed with depression (n = 19). 85 In addition, the G allele was inversely correlated with parasympathetic tone, which was associated with reduced anxiety in healthy participants (n = 1141). 86 Thus, the rs6295 G allele associates with depression and anxiety phenotypes, while the C allele may be protective.…”

Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder

“…A meta‐analysis showed that the G allele was present in 50% of Caucasians but only in 21% of Asians, but only the Asians studies showed a significant association of the polymorphism with treatment response (Kato & Serretti, 2010). Another study showed an association of the C/C genotype and response to treatment with Citalopram in geriatric patients (Scutt et al., 2018). While there are a lot of unexplained inconsistencies between studies, some studies (Lemonde et al., 2004; Serretti et al., 2004) have made a strong argument regarding the contribution of the polymorphism to pharmacogenetics of antidepressants.…”

The Influence of Pharmacogenetics in the Clinical Use of Antidepressants

“…In a study conducted with 65 patients, the results showed that the G allel carriers of 5HT1A receptors might be more resistant to antidepressant treatment (15). In a study on 19 geriatric patients using citalopram, remission rates were found different in diverse 5HT1A genotypes (16). On the other hand in other clinical studies, no relationship was found with SSRI treatment success and 5HT1A receptor polymorphism (17,18).…”