Abstract

Background: Depression remains a global health challenge, with many patients failing to achieve sustained remission using conventional treatments. This randomized, double-blind, placebo-controlled trial compared the efficacy of repetitive transcranial magnetic stimulation (rTMS) and Fluoxetine (an SSRI) in treating major depressive disorder (MDD).
Objective: This study compared the efficacy of rTMS to Selective Serotonin Reuptake Inhibitors (SSRIs) in treating depression.
Methods: Forty adults with MDD were randomized to receive either rTMS (twice weekly for 6 weeks; n = 20) or Fluoxetine (20 mg/day for 6 months; n= 20). Sham procedures controlled for placebo effects. Depression severity was measured using the Hamilton Depression Rating Scale (HAM-D) at baseline, 6 weeks, 6 months, and 12 months. Data were analyzed via mixed-design ANOVA.
Results: Both treatments significantly reduced HAM-D scores over time (p < .001, η² = 0.997). While no main effect of treatment was observed (p =.15, η² = 0.054), rTMS showed superior long-term efficacy. At 6 months, rTMS achieved near-remission (mean HAM-D = 0.20 vs. 1.10 for Fluoxetine; p < .001, 95% CI [−1.12, −0.68]). At 12 months, rTMS maintained a lower symptom burden (mean HAM-D = 7.30 vs. 9.30; p = .017, 95% CI [−3.92, −0.08]) The time × treatment interaction was significant (p = .017, η² = 0.243), indicating rTMS’s sustained benefit.
Conclusion: rTMS may offer more durable antidepressant effects than Fluoxetine, particularly beyond 6 months. These findings support rTMS as a first-line intervention for MDD, though larger trials are needed to confirm its long-term advantage.

Key words: Depression, Fluoxetine, Neuromodulation, Randomized Controlled Trial, rTMS