White matter hyperintensities (WMHs) have been shown to be associated with the development of late-life depression (LLD) and eventual treatment outcomes. This study sought to investigate longitudinal WMH changes in patients with LLD during a 12-week antidepressant treatment course. Forty-seven depressed elderly patients were included in this analysis. All depressed subjects started pharmacological treatment for depression shortly after a baseline magnetic resonance imaging (MRI) scan. At 12 weeks, patients underwent a follow-up MRI scan, and were categorized as either treatment remitters (n=23) or non-remitters (n=24). Among all patients, there was as a significant increase in WMHs over 12 weeks (t(46)=2.36, P=0.02). When patients were stratified by remission status, non-remitters demonstrated a significant increase in WMHs (t(23)=2.17, P=0.04), but this was not observed in remitters (t(22)=1.09, P=0.29). Other markers of brain integrity were also investigated including whole brain gray matter volume, hippocampal volume, and fractional anisotropy. No significant differences were observed in any of these markers during treatment, including when patients were stratified based on remission status. These results add to existing literature showing the association between WMH accumulation and LLD treatment outcomes. Moreover, this is the first study to demonstrate similar findings over a short interval (ie 12 weeks), which corresponds to the typical length of an antidepressant trial. These findings serve to highlight the acute interplay of cerebrovascular ischemic disease and LLD.