Treatments for vascular depression in older adults: A systematic review

BACKGROUND: Vascular depression (VaD) is a subtype of late-life depression (LLD) associated with cerebrovascular disease, cognitive impairment, and poor response to standard antidepressants. Despite its clinical relevance and association with increased risk of dementia, no specific treatment guidelines currently exist. OBJECTIVES: To systematically review randomised controlled trials (RCTs) on the clinical efficacy of pharmacological and non-pharmacological interventions for VaD in older adults. METHODS: A systematic search of MEDLINE, EMBASE, Web of Science and ClinicalTrials.gov registry identified 7994 records, of which 8 RCTs met inclusion criteria. Studies included participants with late-life VaD. Interventions comprised pharmacological treatments (augmentation with tandospirone and nimodipine) and neuromodulation techniques (rTMS and tDCS). Outcomes included treatment response and remission, change in depressive symptoms, and other clinical outcomes. RESULTS: Augmentation with tandospirone was associated with faster early symptom improvement in three of four trials. Nimodipine improved remission at 2 months and reduced recurrence in one of two trials. Neuromodulation interventions showed promising antidepressant effects and cognitive benefits (based on two trials). Treatments were generally well tolerated. However, study heterogeneity, small sample sizes, and short follow-up durations limited comparability and precluded meta-analysis. The overall certainty of evidence was low to very low. CONCLUSIONS: Evidence on treatment for VaD remains limited, highlighting the need for large, well-designed RCTs and integrated approaches combining vascular risk management with targeted therapies.