Effects of monoclonal antibody therapies on depression in Parkinson's disease and Alzheimer's disease: Systematic review and meta-analysis

BackgroundDepression in Alzheimer's disease (AD) and Parkinson's disease (PD) is common, disabling and difficult to treat. Pathological protein deposition in PD and AD has been associated with late-life depression, and inflammatory and vascular changes have been proposed as key mechanisms underlying depression in neurodegenerative disorders. Monoclonal antibody therapies (mAbs) effectively clear pathological protein aggregates in PD and AD but are associated with cerebral inflammation and microvascular damage.ObjectiveWe conducted a systematic review and meta-analysis to determine whether mAb treatment influences the risk or severity of depression in AD and PD.MethodsCochrane, Ovid MEDLINE/PubMed, PsycINFO and Embase databases were searched for articles published from inception to 8 April 2025. Randomized controlled trials of mAbs for PD or AD reporting a validated measure of depressive symptoms, or depression incidence were included and meta-analyzed.ResultsWe identified 13 studies including 8603 participants (treatment arm: n = 4690, placebo arm: n = 3913). All studies reported depression incidence as an adverse event, but none assessed changes in depressive symptom severity using standardized mood scales. Meta-analysis revealed no significant difference in the incidence of depression with mAb therapy (log risk ratio: -0.24, 95% CI (-0.52, 0.04), p = 0.09).ConclusionsWe observed no significant association between mAb therapy and risk of depression in PD or AD. However, the absence of validated symptom assessments in these trials represents a critical gap in outcome reporting. Future trials should incorporate standardized depressive symptom measures as outcomes to evaluate the potential neuropsychiatric risks of these therapies.