Treatment Response to Bupropion: An Investigation of Changes in Resting-State Functional Connectivity in Patients with Major Depressive Disorder

Rationale: Bupropion’s unique pharmacology as a dopaminergic and noradrenergic reuptake inhibitor distinguishes it from other antidepressants. Studies on a number of other antidepressants have demonstrated modulation of resting-state functional connectivity (rsFC). However, how bupropion affects rsFC in patients with major depressive disorder (MDD) remains unknown. Objectives To identify rsFC changes in MDD patients receiving bupropion treatment relative to a sample of controls. Method Thirty-nine MDD patients received 300mg (titrated from 150mg) Bupropion daily for 6 weeks. 40 controls received no treatment. All participants underwent MRI scans at baseline and after 2 weeks. Mood and symptom severity were assessed at baseline, week 2, and week 6. Comparisons of rsFC were made at baseline and for changes from baseline to the 2-week follow-up. Correlations between symptoms and rsFC were also assessed. Results No significant baseline differences were found between patients and controls. Crossover interaction effects between groups and time were observed. Network analysis identified changed rsFC between the cerebellar network and left superior and middle temporal gyrus. Seed analysis showed changed rsFC between the insula and areas in the sensorimotor and occipital cortex as well as precuneus. No relationships were found between changes in symptoms at week 6 and rsFC changes at week 2. Conclusions This study is the first to examine bupropion’s effects on rsFC in MDD patients, revealing rsFC changes that may be important for bupropion’s mode of action. It provides a foundation for further investigation into bupropion and its underlying mechanisms, which may have important implications for depression treatment.