Tourette Syndrome (TS) is a neurological disorder characterized by a spectrum of motor and vocal tics - involuntary, repetitive movements or vocalizations (1). The onset of these symptoms generally surfaces between the ages of three and nine (2). The severity of the symptoms is commonly measured using the Yale Global Tic Severity Scale (YGTSS). YGTSS is a widely used assessment tool designed to measure the severity and impact of tics in individuals diagnosed with TS, as recommended by the American Academy of Neurology guideline (3). It comprises several domains, including frequency, intensity, complexity, and impairment related to both motor and vocal tics. Despite significant advancements in neuroscience, the etiology of TS remains vague, with hypotheses revolving around abnormalities in certain brain regions (including the basal ganglia, frontal lobes, and cortex), and the neurotransmitters (dopamine, serotonin, and norepinephrine) that mediate nerve cell communication (4).

The intricate pathology of TS is believed to be multifactorial, involving both genetic predispositions and potential environmental influences (5). Adding layers of complexity to the clinical manifestation and management of the condition, TS is often comorbid with other behavioral disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) (6), which is assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS). YBOCS is a standardized assessment tool utilized to measure the severity of OCD symptoms (7, 8). It evaluates the presence and intensity of obsessions and compulsions across several domains, including time spent, distress caused, and interference with daily functioning.

While there is no definitive cure for TS, a multitude of treatment strategies have been adopted to manage the symptoms and improve the quality of life for those affected. These strategies encompass cognitive-behavioral therapy (CBT), pharmacological interventions, deep brain stimulation (DBS), and repetitive transcranial magnetic stimulation (rTMS) (9, 10). Currently the management of Tourette patients consists of the following stages: first, psychological education and social support for mild conditions; second, pharmacological therapy and behavioral intervention; and third, invasive or non-invasive neuromodulation such as DBS or rTMS in severe or refractory cases (11).

Studies that compare the efficacy of DBS and rTMS in TS patients are scarce, mostly due to methodological limitations. Published studies are often conflicting (12–19), thus the development of evidence-based guidance to direct clinical decision-making in the selection of therapeutic regimen for severe or refractory TS is important. Therefore, we aimed to compare the efficacy of DBS and rTMS in TS patients. Our primary objective was to examine change in YGTSS in patients with TS before and after each intervention, and our secondary objectives were to investigate the effect of DBS on different brain areas, and the effect of brain stimulation on OCD symptoms by analyzing the change in YBOCS.

The present study examined the therapeutic efficacy of rTMS and DBS in the treatment of TS and OCD. The results indicate that both rTMS and DBS exhibited effectiveness in improving symptoms in both diseases. Notably, rTMS demonstrated greater efficacy in improving OCD symptoms, while DBS was found to be more effective in TS, as rTMS failed to show effectiveness in the analysis of RCTs.

It is worth noting that few studies have directly compared the efficacy of DBS and rTMS, with most previous investigations primarily focusing on exploring the therapeutic potential of either intervention. Our findings also closely align with the previous meta-analysis by Xiaofeng Lin et al. (25). However, it is important to acknowledge that their study did not include an analysis of sham studies, and subsequent articles incorporating new evidence have been published since then.

Prior studies evaluating the YGTSS have yielded mixed results regarding the effectiveness of rTMS (17–19, 34–38). In our investigation, the YGTSS from RCTs showed no significant difference between the rTMS group and baseline ( Figure 2A ). However, when non-RCTs were included in the analysis, the rTMS group exhibited a significant decrease in YGTSS compared to the baseline ( Figure 2B ). This suggests a potential methodological limitation that has not been previously acknowledged in the literature. Furthermore, our analysis of sham rTMS studies demonstrated a marginally significant difference in YGTSS compared to the baseline, which suggests that the effectiveness seen in non-RCTs is possibly due to a placebo effect.

Conversely, DBS demonstrated a significant decrease in YGTSS compared to baseline, with this decrease observed in both RCTs and non-RCTs. Moreover, the analysis of sham DBS studies indicated no significant difference in YGTSS compared to the baseline, providing further evidence that the symptom reduction associated with DBS is attributable to the stimulation rather than the surgical procedure or a placebo effect. Additionally, DBS exhibited a more pronounced decrease in YGTSS in the thalamic ventrooral region compared to the Gpi, although the number of ventrooral studies that we were able to include in the analysis was limited, so this result should be considered with caution.

Furthermore, the YBOCS was assessed following rTMS and DBS interventions, revealing a significant decrease in compared to the baseline. The analysis of sham rTMS and sham DBS studies demonstrated no significant difference in YBOCS compared to the baseline, this also suggests the effectiveness of rTMS and DBS in these patients was not due to a placebo effect.

While both DBS and rTMS have demonstrated efficacy in patients with TS and OCD, it is important to consider the potential side effects associated with these interventions. In several articles, DBS was associated with more severe side effects, including infections, headaches, dizziness, infection, and an increase in tic severity, as indicated in Supplementary Table S2 .

There are several limitations to consider in our study. Firstly, none of the included studies directly compared DBS and rTMS, which introduces a significant gap in our understanding of their relative efficacy. The lack of direct comparison is primarily attributed to the limited number of studies available on this topic. Furthermore, the heterogeneity in the frequency and location of stimulation between the studies further complicates the comparison of these interventions. Secondly, while our study includes findings from various trials, it is essential to acknowledge the limited number of high-quality randomized controlled trials (RCTs) available on this subject. The scarcity of such trials restricts the strength of evidence supporting our conclusions. Additionally, the potential for publication bias should be considered, as studies with negative or inconclusive results may be less likely to be published, potentially skewing the available evidence base. Thirdly, it is important to acknowledge that not all studies reported adverse effects associated with the therapies under investigation. This missing data regarding adverse effects introduces a potential bias and limits our comprehensive understanding of the safety profiles of DBS and rTMS. Therefore, caution should be exercised in interpreting the adverse effect data presented in our study. Lastly, the large heterogeneity observed across the included studies can be attributed to various factors. One major contributing factor is the diverse patient characteristics within the study populations. Patients differed significantly in terms of age, comorbidities, and medications used, among other factors. The lack of standardized patient selection criteria and control of confounding variables may have influenced the observed heterogeneity and introduced variability in the treatment outcomes.

It is essential to consider these limitations when interpreting the findings of our study, as they highlight areas for further investigation and underscore the need for more rigorous research to establish the comparative efficacy and safety of DBS and rTMS. Future studies should focus on directly comparing DBS and rTMS in randomized controlled trials to provide robust evidence regarding their relative efficacy and safety. Such research should aim to standardize stimulation protocols, patient selection criteria, and outcome measures to minimize heterogeneity and enhance the comparability of findings. Subgroup analysis including demographic variables should be considered in future studies as they might generate different risk ratios. Additionally, efforts should be made to report adverse effects comprehensively to establish a clearer understanding of the safety profiles of these interventions. Addressing these gaps will contribute significantly to optimizing treatment strategies for tic symptoms and obsessional symptoms.

Our study provides valuable insights into the management of TS and OCD, overall showing the effectiveness of rTMS and DBS in treating both diseases, especially in advanced disease. However, the analysis of rTMS effect on TS showed conflicting results in RCTs vs non-RCTs, likely due to the limited number of RCTs or a placebo effect. It is crucial to consider the limitations of the current literature and the lack of direct comparisons between DBS and rTMS. Further randomized controlled trials comparing both modalities directly are needed.