Depression is a common problem among older adults and is further exacerbated by poor treatment response. The vascular depression hypothesis suggests that white matter hyperintensities (WMH) and executive dysfunction are main contributors to treatment non-response in older adults. While a previous meta-analysis has demonstrated the effects of executive dysfunction on treatment response, similar techniques have not been used to address the relationship between WMH and treatment response. Multiple commonly-cited studies demonstrate a relationship between WMH and treatment response, however, the literature on the predictive nature of the relationship is quite inconsistent. Additionally, many studies supporting this relationship are not randomized controlled studies. Critically examining data of well-controlled treatment response outcome studies using meta-analytic methods will allow for an aggregate evaluation of the relationship between WMH burden and treatment response.

A MEDLINE search was conducted to identify regimented antidepressant treatment trials contrasting white matter hyperintensity burden between remitters and non-remitters. Only regimented treatment trials for depressed outpatients aged 50 and older that had a pre-treatment measure of WMH burden and remitter/non-remitter comparison were included. Hedge’s g was calculated for each trial’s treatment effect. A Bayesian meta-analysis was used to estimate an aggregate effect size.

Eight studies met inclusion criteria. The log odds ratios average was significantly less than zero (.25, SE=.12, p=.019), suggesting that there is a significant effect of WMH hyperintensity burden on antidepressant remission status.

The purpose of this meta-analysis was to rigorously evaluate randomized controlled trials to determine the relationship between WMH burden and antidepressant treatment response. Findings revealed that WMH burden predicted antidepressant remission, that is, individuals with high WMH burden are less likely to meet remission criteria compared to individuals with low WMH burden. Results suggest that it may be important to consider vascular depression as a distinct treatment target of alternate interventions.