The depression-executive dysfunction (DED) syndrome and response to antidepressants: a meta-analytic review

The depression-executive dysfunction (DED) model predicts that cognitive impairment, particularly executive dysfunction, is associated with poor response to antidepressant medication. A meta-analysis was undertaken to assess the evidence for this hypothesis.

The PsycInfo and PubMed databases were searched to identify studies that examined response to antidepressant treatment in relation to pre-treatment cognitive performance. Systematic screening yielded 17 eligible publications, providing data for 1269 individuals. Ninety cognitive tests and subtests were used by these studies; 30 were used by more than one study. Weighted mean Cohen's d effect sizes, 95% confidence intervals and Fail Safe Ns were calculated for these 30 tests.

Five cognitive tests provided good discrimination (d(w) > 0.5) between patients who ultimately responded to antidepressant medication and those who failed to respond. One was a test of executive function but the remainder assessed other cognitive domains. Due to the small number of studies the influence of methodological factors, such as participant age and treatment duration, could not be statistically examined. However, a supplementary analysis restricted to nine studies where SSRIs were the only class of antidepressant revealed a similar pattern of results.

Performance on selected tests of executive function and non-executive cognitive functions is associated with response to anti-depressant medication in some populations. The available evidence does not provide strong support for the DED model.