359 Associations between baseline anhedonia severity and clinical response to transcranial magnetic stimulation in adolescents with major depressive disorder

Objectives/Goals: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation therapy FDA-cleared for adjunct treatment of major depressive disorder (MDD) in adolescents. Here, we describe a double-blind, randomized study that explores the use of anhedonia severity as a predictor of treatment response. Methods/Study Population: This study included 41 participants (25 females) aged 12–18 years who had a Children’s Depressed Rating Scale-Revised (CDRS-R) score greater or equal to 40. Participants underwent daily rTMS at either 1 Hz or 10 Hz (randomly assigned) 5 days/week, for 6 weeks. Anhedonia was measured via a composite score using certain items from the CDRS-R and Beck Depression Inventory (BDI)-II. Treatment response was assessed via the Clinical Global Impressions – Improvement (CGI-I) scale. A logistic regression approach was used to estimate the likelihood of clinical improvement from baseline. A linear mixed model of repeated measures was used to assess changes in anhedonia scores over the study duration, across both frequency groups. Results/Anticipated Results: A significant improvement in anhedonia scores was observed across both 1 Hz (p< 0.0001, d=0.8536) and 10 Hz (p<0.0001, d=0.9032) groups. However, no significant group differences (p=0.2559) were observed for 1 Hz (m=5.121, SE=0.450) versus 10 Hz (m=5.894, SE=0.486). Notably, our analysis revealed a significant inverse relationship between changes in anhedonia symptom severity and CGI-I response for both 1Hz (d= -1.1017, SE=0.5003, p=0.0277) and 10 Hz (d= -0.8581, SE=0.3371, p=0.0109) groups. No significant interaction between TMS treatment group and changes in anhedonia or CGI-I scores were observed (p=0.3204). TMS stimulation frequency (1 Hz vs 10 Hz) did not have specific effects on the change in anhedonia scores or CGI-I response. Discussion/Significance of Impact: This study shows that TMS (1 Hz or 10 Hz) can help with specific symptomology in depression via significant decreases in anhedonia and how anhedonia may moderate overall TMS response. Future research should further elucidate predictors or moderators of TMS treatment response to inform clinical decision-making and care for adolescents with MDD.