TMS and rTMS for Mental Health: A Summary of Studies

We’ve gathered recent studies on Transcranial Magnetic Stimulation (TMS) and Repetitive TMS (rTMS) that have been conducted in the area of mental health such as:

• Anxiety / General Anxiety Disorder
• Depression / Major Clinical Depression / Pharmacological Treatment-Resistant Depression
• Insomnia
• Post-Traumatic Stress Disorder

Although still being researched, many findings are highly promising. In order to make this post and the information herein display in a more readable format, a summary of studies will be listed rather than displayed in tabular format.

1.Study Focus: PTSD

Study Title: Theta-Burst Transcranial Magnetic Stimulation for Post-Traumatic Stress Disorder (PTSD)

Location: USA

Year: 2019

No. of Participants: 50

Protocol: 10 days of sham-controlled iTBS, followed by 10 unblinded sessions. Analysis from both participants and clinicians were recorded.

Results / Findings: Depression decreased outside of sham treatments. Significant positive changes found within PTSD-related symptoms, depression, social and occupational function. Concluded that iTBS appears to be a promising new treatment for PTSD.

Link to Study: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02090179/full

2.Study Focus: Treatment-Resistant Major Depression

Study Title: Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans: a Randomized Clinical Trial

Location: USA

Year: 2018

No. of Participants: 164

Protocol: Double-blind, sham-controlled randomized trial over the course of 4 years. Up to 30 sessions for each participant, being allocated either a sham or genuine treatment. 81 had genuine treatment.

Results / Findings: 39% of veterans showed a remission in depressive symptoms.

Link to Study: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-01991293/full

3. Study Focus: Depression

Study Title: Effects of Repetitive Transcranial Magnetic Stimulation on Improvement of Mental Health and Clinical Parameters in Depressed Hemodialysis Patients: a Pilot Study

Location: Korea

Year: 2020

No. of Participants: 14

Protocol: Active and sham treatments over the course of 4 weeks.

Results / Findings: The TMS treatment group showed a significant improvement in the Hamilton Depression Scale when compared to the sham group. Anxiety and Somatization symptoms were also reduced in the TMS group.

Link to Study: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02140966/full

4. Study Focus: Depression

Study Title: Pain Trajectories of Dorsomedial Prefrontal Intermittent Theta Burst Stimulation Versus Sham Treatment in Depression

Location: USA

Year: 2020

No. of Participants: 36

Protocol: Randomized, blind trial with active and sham treatments.

Results / Findings: Pain reduction was found in the TMS group when compared to the sham group. This was constant throughout the trial.

Link to Study: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02196046/full

5. Study Focus: Depression

Study Title: Repetitive Transcranial Magnetic Stimulation for Depression: outcomes in a United Kingdom Clinical Practice

Location: UK

Year: 2015-2017

No. of Participants: 73

Protocol: The study was a retrospective investigation of routinely collected data on patients receiving rTMS between 2015 and 2017. Measures used were the clinician-rated Clinical Global Impression (CGI) and Hamilton Depression Rating Scale (HAM-D), and patient rated Beck Depression Inventory (BDI). The outcome data of 73 patients with TRD were analysed. The sample included patients with co-morbid psychiatric diagnosis.

Results / Findings: The NHS show a similar trend found internationally – there is a significant improvement in depression and anxiety symptoms, according to the Hamilton Depression Scale. The study concludes that the NHS could make financial savings alongside patient improvement by investing in rTMS.

Response and remission rates, respectively, were 40.4% and 25.5% for the HAM-D; 35.6% and 20.8% for the BDI; and 51.1% and 52.1% for the CGI. Effect sizes were medium (0.54, 0.52 and 0.56, respectively). The results show that a UK-based clinical service achieves similar results to those published internationally and that clinical rTMS can have significant impact on symptoms of depression in many patients with TRD. Health services are under pressure to make financial savings, investment in rTMS could reduce the long-term treatment costs associated with TRD.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/30931656

6. Study Focus: Depression

Study Title: Connectivity Guided Theta Burst Transcranial Magnetic Stimulation versus Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant moderate to severe Depression: study protocol for a randomised double-blind controlled trial (BRIGHTMIND)

Location: UK

Year: 2020

No. of Participants: 368

Protocol: double-blind trial, receiving one of two rTMS treatments.

Results / Findings: he primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks postrandomisation. Cost-effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined. Both kinds of rTMS treatment were deemed effective in treating depression. Further studies into rTMS has also been suggested.

Link to Study: https://bmjopen.bmj.com/content/10/7/e038430

7. Study Focus: PTSD

Study Title: Noohi, References in NICE Guidelines 116 for non-pharmaceutical PTSD Treatment in Adults

Location: Iran

Year: 2017

No. of Participants: 30

Protocol and Demographics: Age range (mean): 25-60 (NR) Gender (% female): 0 BME (% non-white): NR. confirmed as PTSD according to the Structured
Clinical Intrview for DSM-IV (SCID) (American Psychiatric Association 1994) criteria considering non-sleep PTSD symptoms.

Results / Findings: All 7 components of Subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication and daytime functioning were significantly higher in PTSD group comparing control.

Link to Study: Download PDF of Sleep Disturbance in War Veterans

8. Study Focus: PTSD

Study Title: Heart rate variability (HRV) and posttraumatic stress disorder (PTSD): a pilot study (on Biofeedback)

Location: USA

Year: 2011

No. of Participants: 20

Protocol: Inclusion criteria: a diagnosis of combat-related PTSD on ICD/DSM criteria

Results / Findings: A pilot study was undertaken to determine if veterans with PTSD (as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist) would show significantly different HRV prior to an intervention at baseline compared to controls; specifically, to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD. The study also aimed at assessing the feasibility, acceptability, and potential efficacy of providing HRV biofeedback as a treatment for PTSD.

The results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD. However, the TAU had no significant effect on either HRV or symptom reduction. A larger randomized control trial to validate these findings appears warranted

Link to Study: https://pubmed.ncbi.nlm.nih.gov/20680439

9. Study Focus: PTSD

Study Title: Electroconvulsive therapy with a memory reactivation intervention for post-traumatic stress disorder: A randomized controlled trial

Location: Canada

Year: 2021

No. of Participants: 28

Protocol: In the Behavioral Arm: Traumatic memory reactivation

Results / Findings: Outcomes were measured in two ways:

• Change in Modified PTSD Symptom Scale (MPSS-SR) score [ Time Frame: Baseline, after ECT treatment course (an average of 4 weeks), and at 3 month follow up ]
• Change in Clinician Administered PTSD Scale for DSM-5 (CAPS-5) score [ Time Frame: Baseline, after ECT treatment course (an average of 4 weeks), and at 3 month follow up ]

Link to Study: https://pubmed.ncbi.nlm.nih.gov/33785406 and https://clinicaltrials.gov/ct2/show/NCT04027452

10. Study Focus: PTSD

Study Title: Randomized Trial of 1 Hz Versus 10 Hz Right Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Posttraumatic Stress Disorder (PTSD)

Location: Florida, USA

Year: 2019

No. of Participants: 44

Protocol: Device: Repetitive Transcranial Magnetic Stimulation, TMS Device, Other Name: NeuroStar chair (Neuronetics, Malvern, PA). One arm was slow prefontal right side rTMS, the other arm was faster on same side, rTMS. 30 treatments over 6 weeks.

Results / Findings: No significant advantage was shown in either 1 Hz or 10 Hz arms, although both did show clear improvement in PTSD and depression symptoms.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/30641346 and https://clinicaltrials.gov/ct2/show/NCT02158663

11. Study Focus: PTSD

Study Title: Watts 2012, referenced in NICE-116

Location: USA

Year: 2012

No. of Participants: NR – 10 female

Protocol: PTSD diagnosis according to ICD/DSM including self-diagnosis.

Results / Findings: not posted in NICE review

Link to Study: No link or ID no. posted in the NICE-116 Evidence Review D: https://www.nice.org.uk/guidance/ng116/evidence

12. Study Focus: PTSD

Study Title: Electroconvulsive Therapy for Traumatic Memories

Location: Canada

Year: 2016-2020

No. of Participants: 28

Protocol: The severity of the traumatic memory related symptoms will be assessed before and after the course of ECT using the Modified PTSD Symptom Scale (MPSS-SR) and the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). Data will be analyzed by comparing the change in overall MPSS-SR scores and CAPS-5 scores pre- and post-ECT between the experimental and control groups. Physiological data will also be collected at each ECT session during the time the participant is listening to the audio recordings. Heart rate and skin conductance will be measured prior to and during listening of the traumatic or non-traumatic memory, in order to determine if there is a change associated with a stress response, and whether this response normalizes in association with reduction of PTSD symptoms with treatment.

Results / Findings: Both groups showed improvement.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/33785406 and https://clinicaltrials.gov/ct2/show/NCT04027452

13. Study Focus: PTSD

Study Title: Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial

Location: USA (?)

Year: 2017

No. of Participants: 103

Protocol: Veterans 18-60 years of age with current combat-related PTSD symptoms were randomized, using a 1:1 ratio in a parallel design, to active (rTMS+CPT) versus sham (sham+CPT) rTMS just prior to weekly CPT for 12-15 sessions. Blinded raters evaluated veterans at baseline, after the 5th and 9th treatments, and at 1, 3, and 6 months post-treatment. Clinician Administered PTSD Scale (CAPS) was the primary outcome measure with the PTSD Checklist (PCL) as a secondary outcome measure. The TMS coil (active or sham) was positioned over the right dorsolateral prefrontal cortex (110% MT, 1Hz continuously for 30min, 1800 pulses/treatment).

Results: Of the 515 individuals screened for the study, 103 participants were randomized to either active (n = 54) or sham rTMS (n = 49). Sixty-two participants (60%) completed treatment and 59 (57%) completed the 6-month assessment. The rTMS+CPT group showed greater symptom reductions from baseline on both CAPS and PCL across CPT sessions and follow-up assessments, t(df ≥ 325) ≤ -2.01, p ≤ 0.023, one-tailed and t(df ≥ 303) ≤ -2.14, p ≤ 0.017, one-tailed, respectively.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/29351885

14. Study Focus: Depression

Study Title: Repetitive transcranial magnetic stimulation (rTMS) for depression: outcomes in a United Kingdom (UK) clinical practice

Location: UK

Year: 2015-2017

No. of Participants: 73

Protocol: The study was a retrospective investigation of routinely collected data on patients receiving rTMS between 2015 and 2017. Measures used were the clinician-rated Clinical Global Impression (CGI) and Hamilton Depression Rating Scale (HAM-D), and patient rated Beck Depression Inventory (BDI). The outcome data of 73 patients with TRD were analysed. The sample included patients with co-morbid psychiatric diagnosis.

Results: Response and remission rates, respectively, were 40.4% and 25.5% for the HAM-D; 35.6% and 20.8% for the BDI; and 51.1% and 52.1% for the CGI. Effect sizes were medium (0.54, 0.52 and 0.56, respectively).

Conclusions: The results show that a UK-based clinical service achieves similar results to those published internationally and that clinical rTMS can have significant impact on symptoms of depression in many patients with TRD. Health services are under pressure to make financial savings, investment in rTMS could reduce the long-term treatment costs associated with TRD.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/30931656

15. Study Focus: Depression

Study Title: Health-related quality of life assessment in depression after low-frequency transcranial magnetic stimulation

Location: France

Year: 2014

No. of Participants: 33

Protocol: In a naturalistic trial, 33 unipolar and bipolar patients with medication-resistant depression were treated with daily low-frequency rTMS over the right dorsolateral prefrontal cortex for 4 weeks. Health-related quality of life was assessed using the SF-36 questionnaire. The SF-36 is a generic, self-administered, and worldwide-used questionnaire, consisting of 36 items describing eight health dimensions: physical functioning, social functioning, role-physical problems, role-emotional problems, mental health, vitality, bodily pain, and general health. Physical component summary and mental component summary scores were then obtained. Depression severity was assessed using the 21-item self-report Beck Depression Inventory. Anxiety severity was assessed using the State-Trait Anxiety Inventory. The SF-36, the Beck Depression Inventory and the State-Trait Anxiety Inventory were assessed before and after low-frequency rTMS. The effect of rTMS treatment on the SF-36 and the clinical outcome was evaluated for significance with the Wilcoxon two-tailed signed-rank test. The reliable change index (RCI) was calculated to determine clinically significant change in the eight dimension and composite scores of the SF-36 from pre-intervention to post-intervention, at the level of individual patients. Effect size (r) was then calculated, r values from 0.1 to 0.29, 0.3 to 0.49 and from 0.5 were considered as indicating small, medium and large effect sizes, respectively. Correlations between improvement in Health-related Quality of Life and improvement in the other rating scale scores were calculated using Spearman’s correlation test.

Findings: There were significant improvements of 37.6% in the mental health (P=0.018), 130 % in the role-emotional problem (P=0.045), 15.5% in the physical functioning (P=0.008), 110.6% in the role-physical problem (P=0.002), 22.4% in the bodily pain (P=0.013) dimensions, 6.1% in the Physical Component Score (P=0.043), and 22,5 % in the Beck Depression Inventory (P=0.002). Eighteen patients (54%) showed clinically significant improvement in one of the two composite scores after RCI calculation. Seven out of the eight SF-36 dimension scores and the two composite scores showed effect sizes ranging from 0.12 to 0.38, indicating small to moderate effect. Significant correlations were found between improvement in the Beck Depression Inventory and improvement in the Mental Component Score, the social functioning, the mental health, the general health, the vitality and the physical functioning dimensions.

Low-frequency rTMS over the right dorsolateral prefrontal cortex improves Health-related Quality of Life in unipolar and bipolar patients with medication-resistant depression. Improvement in mental health-related quality of life is significantly correlated with improvement in depressive symptoms. However, further studies with larger samples and controlled designs are needed to clarify these findings.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/24091070

16. Study Focus: Generalised Anxiety Disorder

Study Title: Impact of repetitive transcranial magnetic stimulation on generalized anxiety disorder in treatment-resistant depression

Location: USA

Year: 2016-2018

No. of Participants: 61

Protocol: As a part of routine clinical service, patients with TRD received right dorsolateral prefrontal cortex (DLPFC) inhibitory rTMS immediately prior to left DLPFC depression treatment delivered according to a US Food and Drug Administration protocol.

Methods: A retrospective investigation of routinely collected data between 2016 and 2018 was undertaken. Measures used were the clinicianrated Clinical Global Impressions-Severity (CGI-S) scale and Hamilton Depression Rating scale (HAM-D), and the patient-rated Generalized Anxiety Disorder scale-7 (GAD-7) and Patient Health Questionnaire (PHQ-9). The outcome data of 61 patients with TRD were analyzed. The sample included patients with comorbid psychiatric diagnoses.

Results: Response and remission rates, respectively, were 17.1% and 27.3% on the GAD-7; 20.7% and 12.5% on the HAM-D; 19% and 24% on the PHQ-9; and 20% and 23.5% on the CGI-S. Post-treatment scores significantly improved on the GAD-7, HAM-D, and CGI-S scales, with medium to large effect sizes (.61, .62, and .86 respectively).

Conclusions: Results indicate the potential value of rTMS in treating anxiety in patients who are referred for rTMS for TRD. Well-designed and adequately powered randomized controlled trials are required to determine clinical recommendations.

Link to Study: https://pubmed.ncbi.nlm.nih.gov/31369662

A Note on Clinical and Cost Efficacy

A study was performed analysing 960 abstracts from rTMS and TMS studies on Depression. The studies must have been published prior to January 2014. Here is the link: https://pubmed.ncbi.nlm.nih.gov/24724996

Interestingly, the conclusion was drawn that although rTMS and TMS performed better than the sham controls and was efficacious (or ‘clinically effective’), the authors posit “the clinical relevance of its efficacy is doubtful”.

Given that this was observed nearly one decade ago, it would be interesting to have another review conducted in the near future. Perhaps new findings have discovered that the area of treatment (i.e. left or right predorsal) make a significant difference in treatment efficacy.

Another meta analysis of pre-2014 published studies on rTMS / TMS for Depression was conducted by another group – who came to exactly the opposite conclusions. Here is the link: https://pubmed.ncbi.nlm.nih.gov/24922485

This analysis found that for individuals who did not benefit from two or more treatments for Depression (literally “anti-depressant treatment failures”), TMS / rTMS was clinically effective and reasonable treatment to consider.

Fast Forward One Decade

Much has changed in the nearly 10 years since these meta analyses were performed and published. More medications are prescribed in the UK and USA, for example, that come with a higher risk of contra-indications and side effects. Patients may not be able to or willing to add more medications to their health plan if it comes with greater risk of side effects.

Furthermore, technologies have become more cost effective and more widely developed. It could well be that TMS and PEMF are more cost-effective and more clinically effective, too — certainly more research is needed.