Trajectories of Response to Bilateral rTMS in Late-life Depression

BackgroundLate-life depression is often resistant to standard treatment (LL-TRD) and presents unique clinical challenges due to comorbidities and cognitive decline. Repetitive transcranial magnetic stimulation (rTMS) is a promising option, yet responses are variable. Identifying trajectories of symptom change in LL-TRD in response to rTMS may clarify this heterogeneity and guide more personalized interventions. MethodsThis secondary analysis of a randomized rTMS trial in late-life depression used group-based trajectory modeling to identify depressive symptom response patterns. Participants aged 60+ were randomly assigned to one of two protocols: (1) bilateral rTMS, with low-frequency stimulation applied to the right dorsolateral prefrontal cortex (DLPFC) and high-frequency stimulation to the left; or (2) bilateral theta burst stimulation, with continuous TBS on the right DLPFC and intermittent TBS on the left. Multinomial regression identified baseline characteristics associated with trajectory membership. ResultsFour symptom trajectories were identified: Nonresponse, Slow Linear Response, Moderate Linear Response and Rapid Response. Higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores were associated with lower odds of Rapid (OR=0.79, 95%CI:0.69–0.90) and Moderate Linear Response (OR=0.87, 95%CI:0.78–0.97), and higher odds of Nonresponse (OR=1.33, 95%CI:1.16–1.52). Benzodiazepine use was associated with lower odds of Moderate Linear Response (OR=0.22, 95%CI:0.08–0.56), while higher baseline anxiety was associated with higher odds of Nonresponse (OR=1.13, 95%CI:1.01–1.26). ConclusionThis study identified four distinct rTMS response trajectories in LL-TRD and found that greater baseline depression severity and anxiety were associated with worse trajectories. These results support early clinical profiling to identify individuals at risk for nonresponse.