Genotyping the serotonin transporter gene polymorphism could be a tool for predicting response to a certain treatment pathway. Patients with the s/s genotype who according to the literature seem to be at risk for a less favorable response to antidepressant monotherapy might particularly benefit from augmentation strategies.
Thus, early lithium augmentation in these patients (with the s/s genotype) could be a promising strategy and might help to reduce the occurrence of treatment resistance in depressive disorders.
Serotonin is an important neurotransmitter believed to play an important role in depression. The variant of this gene affects how much serotonin transporter protein is produced. This protein is involved in reuptake of serotonin in the synaps. Individuals with the short allelic form of this variant showed an increased risk of depression compared to those carrying the long allele but only when exposed to adverse life events or maltreatment. There have been some nonreplications, but these have been outnumbered by the number of replicated findings.
Moreover having the two short alleles of this serotonin transporter gene (s/s) results in poorer response to an antidepressant. According to this new research two short alleles also predict a better response to lithium addition if the antidepressant fails.
Although the definition of treatment resistant depression is not always clear, there are several options for treatment resistant depression resulting in 9 possible steps for treatment resistant depression. I am convinced that especially lithium addition is a very effective treatment strategy if an antidepressant fails and should be preferred above more experimental addition strategies such as atypical antipsychotics. Lithium addition can result in a response rate up to 50% in treatment resistant depression and has been studied in many RCT’s, reviews and meta analysis.
In this published research patients had not responded to several antidepressants during an average of 32 days (SD 12.9):14 patients (30%) received tricyclic antidepressants, 15 patients (30%) SSRI, 15 patients (30%) venlafaxine, two patients (4%) atypical antidepressants (trazodone, nefazodone), one patient (2%) mirtazapine, another patient (2%) tranylcypromine and two patients (4%) antidepressant combination therapies (trimipramine plus paroxetine; amitriptyline plus tranylcypromine).
That brings us immediately to the limitations of this study. The heterogeneity of the preceding antidepressant treatment and the short duration of antidepressant pretreatment. This short duration might not be sufficient to declare nonresponse to an antidepressive trial.
So next time a more homogenous patient sample with evident and clear definition of treatment resistant depression.
In the Cox regression survival analysis, three factors remained as contributors to remission during the observation period: the 5-HTTLPR genotype, the diagnosis of a unipolar/bipolar depression and the existence of psychotic features, but only the 5-HTTLPR genotype reached statistical significance.
The gene coding for the serotonin transporter (5-HTT) has been located on chromosome 17q11.2. A polymorphic region (5-HTTLPR) has been identified upstream of the transcription starting point. It generally consists of either 14 or 16 repeated elements generating a long (l) or a short (s) allele. The s-allele is associated with lower gene expression activity in vitro. This genotype has been connected with the pathogenesis of affective disorders and suicidal behaviour and might be an interesting model for a genotype–environment relationship.
Besides these finding on the serotonin transporter gene,patients with a TRD had a larger number of risk genotypes than treatment responders, who in turn had a greater number of risk genotypes than the healthy controls. This finding supports a model in which the additive small effects of multile risk genes explain depression and treatment resistance