Neurocognitive Effects of Theta Burst Stimulation for Treatment-Resistant Depression in Adults: A Systematic Review and Recommendations for Future Research

Repetitive transcranial magnetic stimulation (rTMS) was cleared by the U.S. Food and Drug Administration (FDA) in 2008 as a treatment for major depressive disorder (MDD). Since then, theta burst stimulation (TBS), a variant of rTMS, has been cleared for the same indication and is becoming more widely used in clinical practice given that it is a relatively more accessible form of neuromodulation for treatment-resistant depression (TRD). Evidence has demonstrated that TBS produces similar antidepressant effects to other forms of neuromodulation therapies including rTMS; however, the neurocognitive effects of TBS are less well understood. Given that neurocognitive impairment is a common feature of MDD that is associated with overall functioning and that few treatments exist to address neurocognitive impairment in TRD, it is crucial to understand the TBS-associated neurocognitive effects. To address this gap in knowledge, a systematic review was conducted to delineate the known neurocognitive effects of TBS for TRD in adults. A total of eight articles and one abstract published between 2005 and 2024 met inclusion criteria. Results suggested that TBS for TRD may produce neurocognitive enhancement across specific neurocognitive domains including executive functioning, attention, working memory, and verbal learning. However, evidence was inconsistent and limited by a small number of studies and significant methodologic issues including small sample sizes, mixed study populations, and heterogeneity of neurocognitive measurement and domains examined. Nonetheless, the available evidence suggested that TBS may be a neurocognitively safe antidepressant treatment with potential neurocognitive enhancing effects. Additional research is warranted to optimize TBS and would benefit from advanced methodologic designs inclusive of comprehensive neurocognitive assessment.