Stressful life events, cognitive symptoms of depression and response to antidepressants in GENDEP

Background: The occurrence of stressful life events (SLEs) has been shown to predict response to antidepressants; however, results are inconsistent. There is some evidence to suggest that SLEs prior to treatment are associated with greater cognitive symptoms at baseline and may therefore predict changes in these symptoms specifically. Methods: GENDEP, a prospective part-randomised pharmacogenomics trial, collected longitudinal data on the symptoms of patients with major depression treated with either a selective serotonin reuptake inhibitor (SSRI, escitalopram) or a tricyclic antidepressant (TCA, nortriptyline). Data on life events experienced in the 6 months preceding treatment measured using the List of Threatening Experiences Questionnaire (LTE-Q) were available for 728 participants. Results: Both the occurrence and number of SLEs were associated with greater cognitive but not mood or neurovegetative symptoms prior to treatment. Those who reported SLEs also experienced a greater decline in cognitive symptoms during treatment with escitalopram, but not with nortriptyline. Limitations: Life events were measured retrospectively using a self-report checklist and are therefore subject to a number of biases especially in the context of depressive illness. Conclusions: These findings are in line with cognitive theories of depression and suggest that symptomatic heterogeneity may have contributed to inconsistencies in studies reported to date. Our results also tentatively suggest a clinically relevant drug specific effect of SLEs. Specifically, those reporting stress may benefit more from treatment with SSRIs than TCAs.