Some studies have suggested that noradrenaline reuptake inhibitors (NARIs) are more effective in the more severe depressions. The GENetic and clinical Predictors Of treatment response in Depression (GENPOD) study was designed to test two primary hypotheses:

1. those with the ‘l/l’ genotype of 5-HTTLPR would respond better to an SSRI than a NARI

2. those with more severe depression would show better response to a NARI than a selective serotonin reuptake inhibitor (SSRI).

The current paper reports the findings for the clinical predictor. The study recruited 601 individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory (BDI). They were randomised to either citalopram 20mg daily or reboxetine 4mg twice daily. The main outcome was depressive symptoms measured by the BDI total score 6 weeks after randomisation. Overall, 91% of patients were followed up at 6 weeks (citalopram: n = 274, reboxetine: n = 272).

The study found little evidence to support an interaction between treatment and severity of depression (interaction term: 0.02, 95% CI, 70.59 to 0.62, p = 0.96).  The findings did not change after adjustment for potential confounders: age, gender, employment status, history of depression, number of life events and social support (interaction term: 0.06, 95% CI 70.54 to 0.66, p = 0.85).

The researchers conclude that treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care. They note however that “given the multifaceted nature of depressive illness, perhaps it is not surprising that a single factor in isolation is not predictive of treatment response. More consideration of the wider picture in terms of biological, psychological and social factors may be required in order to move towards the goal of tailoring treatment. Furthermore, it may be useful to focus on examining different patterns of symptoms that may have greater value in discriminating outcomes.”