Studies
Studies
Summary of Research Findings
(compiled by Neuralia TMS)
While the information provided in the consent form references the results of numerous studies regarding the efficacy of TMS, it is important to note that summarising scientific evidence from multiple sources can be challenging.
It is important to understand that the quality, strength, and findings of individual studies vary significantly. Some studies may have limitations that affect their outcomes, and results should not be interpreted as universally applicable or conclusive. Systemic reviews and meta analyses, which aggregate data from multiple randomised controlled trials, generally represent higher-quality evidence and provide a more comprehensive view of treatment efficacy.
As such, many of the studies we reference are meta-analyses. While these provide a broad understanding of TMSoutcomes, they may still contain inherent variations due to differences in study designs, patient populations, treatment protocols, and interpretation of results. Consequently, there remains a possibility of misinterpretation or overgeneralisation of the findings. We encourage you to discuss any questions or concerns with your treating psychiatrist to ensure you have a clear understanding of what TMS may offer in your individual case.
Target Location: Left or Right Prefrontal Cortex
Length of Course: 35 sessions
Target Location: Right Prefrontal Cortex
Length of Course: 15 sessions
Target Location: Medial Prefrontal Cortex
Target Location: Right Prefrontal Cortex
Length of Course: 10 sessions
Target Location: Motor Cortex or Dorso-lateral Prefrontal Cortex
Length of Course: 10 sessions
Target Location: Medial Prefrontal Cortex
Target Location: Motor Cortex or Prefrontal Cortex
Length of Course: 10 sessions
Target Location: Auditory Cortex
Length of Course: 10 sessions
Target Location:Motor Cortex
Length of Course: 10 sessions
Target Location:Prefrontal Cortex
Length of Course: 10 sessions
Target Location:Prefrontal Cortex
Length of Course: 10 sessions
Depression
Target Location: Left or Right Prefrontal Cortex Length of Course: 35 sessions
Chronic Pain
Target Location: Motor Cortex or Dorso-lateral Prefrontal Cortex Length of Course: 10 sessions
Migraines/Headaches
Target Location: Motor Cortex or Prefrontal Cortex Length of Course: 10 sessions
Parkinson’s Disease (motor symptoms)
Target Location: Motor CortexLength of Course: 10 sessions
Depression
In the meta analysis by Vida et al in 2023 titled “Efficacy of repetitive transcranial magnetic stimulation (rTMS) adjunctive therapy for major depressive disorder (MDD) after two antidepressant treatment failures: meta-analysis of randomised sham-controlled trials” the response rate was almost two and a half times more with active rTMS treatment (RR: 2.25, NNT: 6.1) compared the sham group (those not getting TMS). This difference was even more pronounced when analysing remission rates. Based on the 9 analysed studies, nearly 36% of the TRD patients with rTMS treatment achieved remission (in the absence of Maintenance TMS). [1]
PTSD
Target Location: Right Prefrontal Cortex
Length of Course: 15 sessions
A recent meta-analysis by Harris et al in 2021 included 19 studies (376 participants) and revealed a large positive effect of TMS on PTSD symptoms: d = 1.17, 95% confidence interval (CI) = [0.89–1.45], p < 0.001.
This result comes from a review of 19 studies involving 376 people, showing that TMS treatment has a strong positive impact on reducing PTSD symptoms. The number “d = 1.17” is a way to measure how big the effect is, and anything above 0.8 is considered a large effect. So, 1.17 indicates a strong improvement in PTSD symptoms after TMS.
The “95% confidence interval (CI) = [0.89–1.45]” means that researchers are 95% confident that the real effect of TMS falls between 0.89 and 1.45, which still represents a large positive impact.
Finally, “p < 0.001” shows that the result is statistically significant, meaning there’s a very small chance (less than 0.1%) that these findings happened by random chance. In simple terms, this data strongly supports the idea that TMS is signficantly effective in reducing PTSD symptoms. [2]
OCD
Target Location: Medial Prefrontal Cortex
TMS can be used to treat OCD by targeting the Medial Prefrontal Cortex. At Neuralia, we use a specialised double cone coil that is able to act on deeper nerves than the standard superficial coil.
A meta-analysis by Rehn et al published in the Journal of Psychiatric Research in 2018 examined 18 randomised controlled trials involving TMS for OCD. The analysis found that active TMS was significantly superior to sham TMS in reducing OCD symptoms, with a moderate effect size. Notably, the study also reported that higher frequencies of stimulation and longer treatment durations were associated with better outcomes. Note that his TMS course use deep coil. [3]
Another significant study by Carmi et al, published in the American Journal of Psychiatry in 2019, evaluated the efficacy of dTMS for OCD. This multicenter, double-blind, randomized trial involved 99 patients and found that after 6 weeks of treatment, 38.1% of patients in the active dTMS group achieved a response (defined as a ≥30% reduction in Y-BOCS score), compared to just 11.1% in the sham group. [4]
PLEASE NOTE: For OCD we often use a specialised TMS coil called the double cone coil for our protocols. As per Rossi et al 2021, “Double-cone (or angled butterfly/double) coils are a larger version of figure-8 coils where the two circular windings are angled toward the subject’s head to increase the magnetic field strength in depth as well as the electrical efficiency. Consequently, the double-cone coil E-field penetrates deeper and is less focal than conventional figure-8 coils (Deng et al., 2014, 2013). Double-cone coils have been used to target various brain regions that may be difficult to reach with standard figure-8 coils, such as the leg motor area or medial prefrontal cortex, and were claimed to reach effectively the cingulate, insula, and cerebellum. In studies reviewed, no serious AEs such as seizures were reported (Ciampi de Andrade et al, 2012; Blumberger et al., 2018; Dunlop et al., 2015; Fernandez et al., 2018; Gerschlager et al., 2002; Grossheinrich et al., 2009; Huang et al., 2018; Kreuzer et al., 2015a; Kreuzer et al., 2015b; Modirrousta et al., 2015; Nauczyciel et al., 2014; Popa et al., 2010; Riehl, 2008; Ruohonen and Ilmoniemi, 2005; Sutter et al., 2015). “
ADHD
Target Location: Right Prefrontal Cortex
Length of Course: 10 sessions
The Prefrontal Cortex is the centre for executive functioning (including attention, impulse control/inhibition, working memory, planning, organisation & decision making.
In a study by Chen at al in 2023, a meta-analysis of five RCTs with 189 participants (mean age of 32.78 and 8.53 years in adult and child/adolescent populations, respectively) demonstrated that rTMS was more effective for improving sustained attention in patients with ADHD compared with the control groups (SMD = 0.54, p = 0.001). A secondary analysis also showed that rTMS was more effective for improving processing speed than the control groups (SMD = 0.59, p = 0.002) but not for enhancing memory or executive function. [5]
Sustained Attention: The analysis showed that rTMS (repetitive transcranial magnetic stimulation) was more effective than control treatments (such as sham or placebo) at improving sustained attention in people with ADHD. The effect size (SMD = 0.54) suggests a moderate improvement, and the result was statistically significant (p = 0.001), meaning it’s unlikely to be due to chance. [5]
Processing Speed: In a secondary analysis, the study found that rTMS also improved processing speed (how quickly participants could complete tasks) more than the control groups. This improvement was slightly larger (SMD = 0.59) and also statistically significant (p = 0.002).
Memory : However, rTMS did not significantly improve memory compared to control treatments.
In summary, rTMS appears to be helpful for improving sustained attention and processing speed in people with ADHD, but it doesn’t seem to have much effect on memory.
Chronic Pain
Target Location: Motor Cortex or Dorso-lateral Prefrontal Cortex
Length of Course: 10 sessions
RANZCP (Royal Australian and New Zealand College of Psychiatry) 2024 TMS guidelines, To treat Chronic Pain (with neuropathic symptoms), we target the motor cortex to modulate pathways that are sustaining the pain. This is based on the Gate Control Theory of Pain
As per the RANZCP (Royal Australian and New Zealand College of Psychiatry) 2024 TMS guidelines, “A large number of studies have explored the use of TMS in the treatment of chronic pain although these have varied substantially in the pain syndrome targeted and the type of TMS used. Benefits have been seen in studies applying stimulation to the primary motor cortex (M1), to the DLPFC and using deep TMS. The most consistent promising effects seen in clinical trials have been present when stimulation has been applied to the left M1 although it has been pro- posed that optimal treatment should involve a systematic evaluation of multiple treatment targets in an individual patient (Lefaucheur and Nguyen, 2019).
A meta-analysis conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on chronic pain identified no overall effect of TMS across chronic pain conditions, although there was a significant short-term analgesia in neuropathic pain conditions only (Che et al., 2021). Furthermore, significant analgesic effects in chronic pain were demonstrated with stimulation of the M1 site although optimal protocols have not yet been confirmed (Lefaucheur and Nguyen, 2019). ”
Based on the MDPI article titled Transcranial Magnetic Stimulation to Treat Neuropathic Pain: A Bibliometric Analysis, the response rate for TMS in treating chronic neuropathic pain ranges between 30% and 40%. This means that approximately 30-40% of patients treated with TMS experience significant pain relief compared to placebo. [6]
This response rate is considered moderate and suggests that while TMS can provide substantial pain relief for some patients, it is not universally effective. The efficacy of TMS tends to vary depending on individual factors, the type of neuropathic pain being treated, and the stimulation protocol.
This was similar to results found by the Walton Centre’s trial, which is the only NHS (National Health Service) in the UK conducting TMS specifically for chronic pain.
Fibromyalgia
Target Location: Medial Prefrontal Cortex
In a meta analysis by Su et al in 2021, Pain 16 randomised controlled trials were compared in terms of reduction of pain intensity. All comparisons underwent meta-analysis, which revealed significantly less pain in the rTMS group after treatment (SMD, −0.751, 95% CI, −0.991 to −0.511, I2 = 35.9%). [7] Here’s a breakdown of the numbers:
Pain Reduction After Treatment: The meta-analysis looked at 16 studies and found that people in the rTMS treatment group experienced significantly less pain compared to others. The standardized mean difference (SMD) was -0.751, meaning there was a moderate reduction in pain. A negative number here shows that pain decreased. The 95% confidence interval (CI) of -0.991 to -0.511 means the researchers are confident that the true reduction in pain falls within this range. The “I² = 35.9%” refers to how consistent the studies were with each other, with a lower percentage indicating less variability between studies. [7]
No Publication Bias: The funnel plot and Egger test are ways to check if the results might be skewed because only certain studies were published (called publication bias). A “p = 0.88” means there’s no evidence of publication bias, which supports the reliability of the findings. [7]
Pain Reduction Over Time:
Two Weeks to One Month Follow-Up: The studies showed that the reduction in pain was still significant after two weeks to one month, with an SMD of -0.516 (again, a moderate decrease in pain). [7]
One and a Half to Three Months Follow-Up: Even after one and a half to three months, the reduction in pain remained significant, with an SMD of -0.588. [7]
The “I²” values indicate how similar the results were across the studies. At two weeks to one month, I² was 0.0%, meaning there was almost no variation between the studies. For the longer follow-up, I² was 52.6%, indicating more variability between the studies. [7]
Overall, these findings suggest that rTMS treatment significantly reduces pain, and the effect lasts for several months after the treatment ends. There was no sign of bias in the studies, meaning the results are likely reliable.
Migraines/Headaches
Target Location: Motor Cortex or Prefrontal Cortex
Length of Course: 10 sessions
To treat Migraine (with neuropathic symptoms), we target the motor cortex/prefrontal cortex to modulate pathways that are sustaining the pain
In a 2022 study by Zhong et al, a meta-analysis combined results from 8 studies and found that rTMS, particularly when applied to the left dorsolateral prefrontal cortex (LDLPFC), significantly reduced how often people experienced migraine attacks. Random effects analysis showed an effect size of −1.13 [95% confidence interval (CI): −1.69 to −0.58] on the frequency of migraine attacks, indicating that rTMS was more effective for decreasing migraine attacks than the sham rTMS. The effect size being -1.13, meant that migraine frequency dropped signficantly in those treated with rTMS compared to those who got a fake (sham) treatment. The confidence interval (CI: -1.69 to -0.58) shows that researchers are confident the true effect is somewhere within that range. In simpler terms, the confidence interval shows that rTMS reduces migraines, and researchers are 95% sure that the true amount of reduction is somewhere between a moderate and a large effect.
Tinnitus
Target Location: Auditory Cortex
Length of Course: 10 sessions
TMS can be used to treat Tinnitus by targeting either the Left or Right Auditory Cortex. For this we use a specialised MRI guided navigation system called Neuronavigation.
The systematic review and meta-analysis of 29 randomised studies with 1,228 patients found that repetitive transcranial magnetic stimulation (rTMS) was effective in reducing symptoms of chronic tinnitus. The response rate showed significant improvements in Tinnitus Handicap Inventory (THI) scores compared to sham-rTMS at several intervals: [9]
- 1 week post-intervention: Mean difference (MD) of -7.92 (95% CI: -14.18, -1.66)
- 1 month post-intervention: MD of -8.52 (95% CI: -12.49, -4.55)
- 6 months post-intervention: MD of -6.53 (95% CI: -11.40, -1.66)
This indicates that about 40-60% of patients experienced meaningful symptom relief, with effects lasting up to six months after treatment. However, it should be noted that the response rates can vary, and the efficacy of rTMS needs further validation in larger trials to confirm safety and long-term benefits.
As per Rossi 2021 et al, “there is a risk of worsening hyperacusis by performing stimulations applied over the auditory cortex, near the ear, in patients with rTMS indicated for the treatment of tinnitus, especially when hyperacusis was already present before rTMS (Lefaucheur et al., 2012). More generally, pre-existing auditory symptoms were found to be possibly aggravated by rTMS applied over the auditory cortex in 1–2.2% of patients treated for tinnitus or auditory hallucinations. This risk can be reduced with hearing protection.
Parkinson’s Disease (motor symptoms)
Target Location: Motor Cortex
Length of Course: 10 sessions
To treat the movement symptoms of Parkinson’s Disease we target the motor cortex to modulate pathways that the nerves regulating motor movement.To measure improvements in motor symptoms, the study by Zanjani et al 2015 used scores from the Unified Parkinson’s Disease Rating Scale (UPDRS), particularly sections II (which focuses on daily activities) and III (which focuses on motor function). [10] Lower scores on these sections indicate improvement.
1. Key Findings:
- Short-term Effects: When looking at the short-term effects (up to 1 day after treatment), active rTMS (real stimulation) significantly improved motor symptoms, as shown by a 3.8-point improvement in UPDRS III scores compared to the sham group (fake treatment). The effect size (Cohen’s d of 0.27) indicates that the improvement was modest but noticeable. [10]
- Long-term Effects: One month after treatment, the difference in motor improvement between the active and sham groups was not statistically significant, but there was still a 6.3-point improvement in motor symptoms from baseline in the active rTMS group. [10]
- No Placebo Effect: The placebo effect (improvement due to belief in treatment, not the treatment itself) was not seen, as those in the sham group did not show significant improvement in motor symptoms (UPDRS III scores). [10]
2. Conclusion: While rTMS targeting the M1 showed some positive effects on motor symptoms in the short term, especially right after treatment, the long-term benefits were less clear. The researchers recommend more studies to confirm these findings and better understand the effects of rTMS in PD treatment. In summary, rTMS may help improve movement problems in Parkinson’s patients, but the improvements are more noticeable in the short term, and further research is needed to draw stronger conclusions.
Post Stroke Cognition
In a systematic review by Gao et al , a total of 8 trials was included and 336 participants provided data for meta-analyses. Large effects were found for rTMS + cognitive training on global cognition (g = 0.780, 95 % CI = 0.477-1.083), executive function (g = 0.769, 95 % CI = 0.291-1.247), working memory (g = 0.609, 95 % CI = 0.158-1.061) and medium improvement on ADL (g = 0.418, 95 % CI = 0.058-0.778) were seen. [11]. While, no effects were found on memory or attention. Subgroup analyses showed that combinations of phase of stroke onset, rTMS frequency, stimulation site and stimulation sessions were potent factors that modulate the effects of rTMS + cognitive training for cognitive function.
Here’s a breakdown of the key findings in simpler terms:
Participants and Scope: The study analysed data from 336 participants across 8 trials, all aimed at evaluating how well rTMS combined with cognitive training works to improve brain function. [11]
Large Effects: The combination of rTMS and cognitive training showed significant improvements in:
Global cognition (overall mental abilities), with a large effect size (g = 0.780), meaning it had a strong positive impact.
Executive function (skills like planning, problem-solving, and organizing), with another large effect size (g = 0.769).
Working memory (the ability to hold and use information in the short term), with a noticeable improvement (g = 0.609). [11]
Medium Improvement in Daily Living: There was a moderate improvement in activities of daily living (ADL), which means that rTMS helped participants perform everyday tasks better (g = 0.418). [11]
No Improvement in Memory or Attention: The treatment combination did not show significant improvements in memory or attention.
Subgroup Analysis: The study also found that certain factors, like the phase of stroke recovery, rTMS frequency, the part of the brain being stimulated, and the number of treatment sessions, influenced how effective the rTMS and cognitive training were for improving cognitive functions.
In summary, combining rTMS with cognitive training significantly improved general cognition, executive function, working memory, and daily activities, but had no effect on memory or attention. Additionally, certain treatment variables could influence the effectiveness of the therapy.
Nicotine Addiction
Target Location: Prefrontal Cortex
Length of Course: 10 sessions
The Prefrontal Cortex is the centre for executive functioning (including attention, impulse control/inhibition, working memory, planning, organisation & decision making. Impulse control being an important aspects to target when it comes to treating addictions.
Li et al in 2013, produced a study investigated whether high-frequency repetitive transcranial magnetic stimulation (rTMS) could reduce cigarette cravings in people who are dependent on nicotine. [12]
The results were as follows. Stimulation of the left DLFPC with real, but not sham, rTMS reduced craving significantly from baseline (64.1± 5.9 vs. 45.7±6.4, t = 2.69, p = 0.018). When compared to neutral cue craving, the effect of real TMS on cue craving was significantly greater than the effect of sham TMS (12.5 ±10.4 vs. −9.1±10.4; t = 2.07, p = 0.049). More decreases in subjective craving induced by TMS correlated positively with higher Fagerström Test for Nicotine Dependence (FTND) score (r = 0.58, p = 0.031) and more cigarettes smoked per day (r = 0.57, p = 0.035). [12]
Here’s a breakdown of the findings
Participants: Sixteen people who were nicotine-dependent but not actively seeking treatment participated in the study.
Study Design: The participants were randomly assigned to receive either:
Real rTMS: High-frequency (10 Hz) stimulation applied to the left dorsolateral prefrontal cortex (DLPFC).
Sham rTMS: A fake version of the treatment (like a placebo), where it looks and feels like rTMS but doesn’t actually stimulate the brain.
Procedure: The participants were exposed to smoking cues (things that might make them want to smoke) before and after rTMS treatment and asked to rate how much they craved a cigarette after each exposure.
ResultsReduced Cravings:
For those who received real rTMS, cravings significantly decreased after the treatment, from a baseline craving score of 64.1 to 45.7 (on a scale out of 100). This reduction was statistically significant (p = 0.018), meaning it is unlikely to have happened by chance. [12]
In contrast, the sham rTMS group did not show a significant reduction in craving.
Comparison to Neutral Cues: When comparing the real rTMS effect with neutral (non-smoking) cues, the reduction in cravings was much greater in the real rTMS group compared to the sham group.
Correlation with Nicotine Dependence: The more dependent a participant was on nicotine (measured by the Fagerström Test for Nicotine Dependence) and the more cigarettes they smoked per day, the larger the reduction in craving after real rTMS. This suggests that people with higher nicotine dependence experienced a greater benefit from the rTMS.
Conclusions
rTMS Reduced Cravings: A single session of high-frequency rTMS to the left DLPFC significantly reduced the urge to smoke when exposed to smoking cues.
Potential Smoking Cessation Aid: This suggests that rTMS could be helpful as part of a smoking cessation treatment plan, though more research is needed to confirm its effectiveness over the long term.
In summary, this study shows that rTMS may help reduce cravings in nicotine-dependent people, especially those with higher nicotine dependence. More research is needed to explore how it could be used to help people quit smoking.
Alcohol Addiction
Target Location: Prefrontal Cortex
Length of Course: 10 sessions
The Prefrontal Cortex is the centre for executive functioning (including attention, impulse control/inhibition, working memory, planning, organisation & decision making. Impulse control being an important aspects to target when it comes to treating addictions.
A a systematic review and meta analysis by Mehta et al 2024 reports on the use of repetitive transcranial magnetic stimulation (rTMS) to treat alcohol use disorder (AUD) and other substance use disorders (SUDs). [13] Here is a breakdown of the findings.