Major depressive disorder (MDD) is one of the most prevalent mental illnesses and, despite the availability of multiple treatment options, remains difficult to treat for a substantial proportion of patients. Repetitive transcranial magnetic stimulation (rTMS) is an important therapeutic approach for depression, modulating brain activity through targeted magnetic pulses in a non-invasive manner. This review examined scientific evidence from clinical trials, large-scale analyses, and laboratory investigations regarding the effectiveness and safety of rTMS, as well as its role within contemporary therapeutic strategies for depression. In addition to conventional rTMS, the review addresses theta-burst stimulation (TBS), deep TMS, and various approaches aimed at enhancing treatment efficacy or accelerating clinical response, while also discussing the practical utility of different stimulation devices. rTMS applied to specific regions of the prefrontal cortex has demonstrated significant antidepressant effects, and intermittent theta-burst stimulation (iTBS) appears to achieve comparable outcomes within a shorter time frame. Research further indicates that rTMS is associated with neurobiological changes in brain connectivity, modulation of neurotransmitter systems, and the promotion of neuroplasticity. Across studies, rTMS is generally considered safe, with reported adverse effects being mild and transient. However, further research is needed to optimize stimulation protocols, clarify medium and long-term effects, individualize treatment approaches, and determine the durability of therapeutic benefits.

Background: Intermittent theta burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS), has gained increasing attention as a time-efficient neuromodulation protocol for major depressive disorder (MDD). However, its clinical effectiveness in individuals with co-occurring depression and anxiety remains insufficiently characterized. This systematic review aimed to evaluate clinical outcomes, including depressive and anxiety symptom severity, response, and remission, following rTMS in individuals with major depressive disorder and elevated anxiety symptoms. The primary outcome was the reduction of depressive and anxiety symptoms, while secondary outcomes included response and remission rates, adverse events, and potential predictors of treatment response. Methods: A systematic search was performed following the PRISMA guidelines in the following databases: PubMed, Scopus, Embase, PsycInfo, Web of Science, Elsevier, Google Scholar. The protocol was registered in PROSPERO (CRD420251117784). Six studies that met the inclusion criteria were selected as eligible; these included one randomized controlled trial, one controlled clinical trial, three open-label studies, and one retrospective study on iTBS alone or compared to conventional 10 Hz rTMS or pharmacotherapy. iTBS has demonstrated safety and efficacy in reducing depressive and anxiety symptoms. The response rate ranged between 30 and 60%, and the remission rate between 10 and 40%. Regarding comparative findings, the results are mixed, with some studies showing superior or comparable improvements to 10 Hz rTMS and others reporting no significant differences. Reported treatment outcomes were largely influenced by age, baseline severity, medication status, and comorbid anxiety. Antipsychotics, anticonvulsants, and benzodiazepines were associated with attenuated clinical benefit, and bupropion use was associated with increased response. Conclusions: Current evidence supports iTBS as an effective, well-tolerated, and time-efficient intervention for adults with depression and comorbid anxiety. However, variability in treatment outcomes and limited mechanistic data highlight the need for larger, harmonized, and mechanistically informed randomized trials to refine stimulation parameters, improve patient stratification, and clarify the neurobiological substrates of treatment response.