Early improvement of executive test performance during antidepressant treatment predicts treatment outcome in patients with Major Depressive Disorder

Executive dysfunctions frequently occur in patients with Major Depressive Disorder and have been shown to improve during effective antidepressant treatment. However, the time course of improvement and its relationship to treatment outcome is unknown. The aim of the study was to assess the test performance and clinical outcome by repetitive assessments of executive test procedures during antidepressant treatment. Executive test performance was assessed in 209 patients with Major Depressive Disorder (mean age 39.3 +/- 11.4 years) and 84 healthy controls five times in biweekly intervals from baseline to week 8. Patients were treated by a defined treatment algorithm within the early medication change study (EMC trial; ClinicalTrials.gov NCT00974155), controls did not receive any intervention. Cognitive domains were processing speed, cognitive flexibility, phonemic and semantic verbal fluency. Intelligence was assessed at baseline. Depression severity was tested once a week by the Hamilton Depression Rating Scale (HAMD(17)). 130 patients (62%) showed executive dysfunctions in at least one of four tests at baseline. Linear mixed regression models revealed that the course of depression severity was associated to the course of cognitive flexibility (p = 0.004) and semantic verbal fluency (p = 0.020). Cognitive flexibility and semantic verbal fluency may be candidates easily to apply for therapy response prediction in clinical routine, which should be tested in further prospective studies.