Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial

Abstract

It is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.

Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial

“…It is of note, however, that baseline severity in CoBalT was similar to other RCTs of depression in the UK. 109,185,186 The CoBalT sample was nevertheless more ill in terms of chronicity, number of previous episodes, comorbidities and non-response to medication. This suggests that to capture the extent of illness that we see clinically then we need to account for both severity and chronicity, especially in those whose symptoms are resistant to antidepressants.…”

A Neurobiological Hypothesis of Treatment-Resistant Depression – Mechanisms for Selective Serotonin Reuptake Inhibitor Non-Efficacy

“…In addition, a more recent larger meta-analysis supported the hypothesis that 5-HTTLPR is involved in the interaction between stress and depression (Karg et al, 2011). Superior response to SSRIs in depressed patients with the long allele versus short allele has been reported (Smits et al, 2008; Gressier et al, 2009; Huezo-Diaz et al, 2009; Min et al, 2009; Illi et al, 2011), although some studies fail to show allelic effects (Lewis et al, 2011). Although description of the functional attributes of the serotonin polymorphism have been contradictory (Karg et al, 2011), clinical data would prompt us to suspect that the short allele is associated with an inability of the serotonin transporter to cope with excess synaptic 5-HT in the somatodendritic raphe area but this statement remains speculative.…”

Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response

“…However, there are also contradictory studies of no influence of 5-HTT gene variation on response to SSRIs in Caucasian patients with MDD (e.g. Lewis et al, 2011), and in none of the three available genome-wide association studies (GWAS) on antidepressant treatment response was 5-HTT gene variation found to be associated with treatment response (see meta-analysis by GENDEP Investigators, 2013). Besides ethnicity, etiological heterogeneity, high complexity of the clinically defined phenotype, environmental factors, low statistical power of the individual studies and random error in the absence of a true effect, another potential confounder of the presently available pharmacogenetic studies might be epigenetic processes such as methylation of the cytosine pyrimidine ring in CpG dinucleotides, which are flexible, temporally dynamic and functionally highly relevant mechanisms suggested to shape disease risk as well as treatment response in MDD (Menke et al, 2012;Schroeder et al, 2012;Frieling and Tadic, 2013).…”