We are often asked about rTMS for depression, particularly whether it is available on the NHS for patients in Scotland. Below, we explore the evidence to support the use of rTMS for depression and look at how patients might access rTMS in Scotland.

Introduction

This is not intended to be a comprehensive review of rTMS. It is a summary of some of the key findings, outcomes, and reports which have influenced our recommendations about this form of treatment.

What is repetitive Transcranial Magnetic Stimulation (rTMS)

Basic principles

rTMS (commonly referred to as TMS) is a non-invasive neuromodulation treatment for depression. It is based on the principle that an external pulsed magnetic field can, by the principle of induction, change the excitability of cortical neurones. This is an extension of Faraday’s law, which explains how bicycle dynamos and electric motors work.

History of rTMS

• 2008: The first system for rTMS for major depressive disorder was approved by the Food and Drug Administration (FDA) in the USA.
• 2013: Approval is given for rTMS devices for treating migraines with aura.
• 2018: The FDA approves rTMS for treating OCD.
• 2020: FDA approval of 'deep TMS' devices for smoking cessation.
• 2021: rTMS is approved for treating anxiety comorbid with depression.

What does treatment involve?

No anaesthetic is required, and patients will sit very still in a chair whilst the 'coil' is positioned over the head. One of the most common targets for stimulation is the dorsolateral prefrontal cortex, which is in the frontal part of the brain. Most people will typically have daily treatment (20-30 minutes) for 2-4 weeks, with treatment programmes consisting of 15-20 treatment sessions. Some treatment regimes can involve delivering treatment twice a day for two weeks.

There are very few side effects. Whilst the treatment is noisy (the machine makes a loud 'clicking' noise), most people only experience some minor tingling/ unpleasant skin sensations.

Is there evidence to support its use?

The National Institute for Health and Care Excellence (NICE) state:

"The evidence on repetitive transcranial magnetic stimulation for depression shows no major safety concerns. The evidence on its efficacy in the short-term is adequate, although the clinical response is variable. Repetitive transcranial magnetic stimulation for depression may be used with normal arrangements for clinical governance and audit." (NICE, 2015)

The Royal College of Psychiatrists report that:

"The international scientific community has evaluated the available evidence in administration of rTMS in both clinical and research setting and has developed a standard safety protocol…International studies have reported rTMS as generally a safe treatment modality." (RCPsych, 2017)

Systematic review of rTMS

There are over 20 systematic reviews and meta-analyses of rTMS. Because it is possible to do blinded trials (patients don't automatically know if they are getting active treatment or 'sham' treatment), there are lots of randomised controlled trials (RCTs) of rTMS. Patient populations in clinical trials are broadly similar:

• About 70% of patients have failed to respond to ≥ 2 antidepressant treatment trials (Christmas & Matthews, 2020). This means that they are not very unresponsive to treatment, but will probably be similar to many patients being referred by GPs to mental health services for more specialist treatment of their depression.
• In just under one-third of studies, patients have failed to respond to only one previous treatment.
• Only about 45-50% of patients have 'severe' depression on HRSD-17. Most patients have symptom scores in the 'moderate' range.

The overall effect size (against sham-TMS) is 0.33 (Health Quality Ontario, 2016). The effect size is a measure of the size of the different between two group, with larger numbers indicating a greater difference between two treatment groups. An effect size of 0.33 is very similar to that of antidepressant drugs vs placebo.

rTMS vs ECT

All reviews that have compared rTMS to ECT have concluded that ECT is more effective than rTMS (Berlim et al, 2013; Ren et al, 2014). The size of this difference is notable and is about six points on the Hamilton Rating Scale for Depression (HRSD). The difference between most antidepressants and placebo is about 3-4 points.

Limitations of the evidence

Many clinical trials are relatively short and will report outcomes after 2-6 weeks. This means that we know much less about whether the effects of rTMS are long-lasting. There are few long-term follow-up studies, but many people will talk about recurrence after rTMS being somewhat similar to relapse/ recurrence after a course of ECT.

Also, most patients (approximately 80%) haven't had ≥3 failed treatment trials (e.g. Kedzior et al, 2015). So we don't know if rTMS is effective for patients who have failed to respond to lots of previous treatments.

Target population

It is likely that certain patient groups may benefit most from rTMS. These suggestions should not be seen as an endorsement for rTMS in any particular case.

rTMS may be a reasonable option for:

• Those with perinatal depression & OCD, where antidepressants may be contra-indicated or there is a strong patient preference to avoid medication. A study of rTMS in 30 pregnant women found no significant adverse effects (Hizli Sayar et al, 2014);
• People who cannot tolerate standard doses of antidepressants, and where all attempts have been made to improve tolerability (e.g. careful dose titration and close monitoring);
• Intolerance to ECT (e.g. marked cognitive adverse effects). However, as indicated above ECT is undoubtedly more effective than rTMS. These differences are likely to be greater for more severe depression and chronic depression.
• Contraindication to repeated anaesthetics.

It is not possible to state that a strong patient preference for rTMS is sufficient to warrant its use, since a range of factors should influence the decision. In many cases, there are likely to be other treatments that are just as likely to be beneficial (for example, lithium augmentation or psychological therapies).

rTMS may be less suitable for:

• Severe forms of depression. In cases where a rapid response is needed, and symptoms are severe, then ECT has much better evidence for effectiveness.
• Those who have tried (and failed to respond) to many different trials of treatment. Most people in rTMS studies are at the lower end of the range of failed treatments (typically 2-3), and we know less about whether it might be effective for those that have have had more than 4-5 treatments.
• Patients with cochlear implants. Although this isn't an absolute contra-indication, we lack sufficient data on safety.

Accessing rTMS in Scotland

At the time of writing, rTMS is not currently available on the NHS in Scotland. Anecdotally, some NHS Boards have successfully referred patients to England to receive rTMS but it is likely that most NHS Boards would be resistant to supporting this unless there are mitigating circumstances and there is a strong case that all other reasonable treatments have been tried.

The only way to access rTMS in Scotland is via private providers. The SmartTMS service in Edinburgh is provided by a company which has TMS clinics throughout other parts of the UK. Patients will need to pay for any treatment, or they may be able to access it via health insurance.

References

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE. Repetitive transcranial magnetic stimulation for depression (IPG 542). London: National Collaborating Centre for Mental Health. http://nice.org.uk/guidance/ipg542

RCPSYCH COMMITTEE ON ECT AND RELATED TREATMENTS. Statement on Repetitive Transcranial Magnetic Stimulation for Depression (Position statement CERT03/17). London: Royal College of Psychiatrists. https://www.rcpsych.ac.uk/docs/default-source/about-us/who-we-are/ectcommittee-repetative-transcranial-magnetic-stimulation-statement-may18.pdf

HEALTH QUALITY ONTARIO. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Ontario Health Technology Assessment Series. 2016; 16(5): 1-66. https://www.ncbi.nlm.nih.gov/pubmed/27099642

EUNETHTA. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depression. Project ID: WP4-ACB-CA-5. Diemen, Netherlands: European Network for Health Technology Assessment. http://www.eunethta.eu/sites/default/files/Assessment_rTMS_final_0.pdf

BERLIM MT, VAN DEN EYNDE F, DASKALAKIS ZJ. Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials. Depression and Anxiety. 2013; 30(7): 614-623. http://doi.org/10.1002/da.22060

REN J, LI H, PALANIYAPPAN L, LIU H, WANG J, LI C, ROSSINI PM. Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014; 51: 181-189. http://doi.org/10.1016/j.pnpbp.2014.02.004

KEDZIOR KARINA K, GELLERSEN HELENA M, BRACHETTI ANNA K, BERLIM MT. Deep transcranial magnetic stimulation (DTMS) in the treatment of major depression: An exploratory systematic review and meta-analysis. Journal of Affective Disorders. 2015; 187: 73-83. http://doi.org/10.1016/j.jad.2015.08.033

CHRISTMAS DMB, MATTHEWS K. Electroconvulsive Therapy and Neuromodulation Therapies. In: Haddad PM, Nutt DJ, editors. Seminars in Clinical Psychopharmacology. 3rd ed. Cambridge: Cambridge University Press; 2020. p. 500-528. https://doi.org/10.1017/9781911623465.018

HıZLı SAYAR G, OZTEN E, TUFAN E, CERIT C, KAĞAN G, DILBAZ N, TARHAN N. Transcranial magnetic stimulation during pregnancy. Archives of Women's Mental Health. 2014; 17(4): 311-315. http://dx.doi.org/10.1007/s00737-013-0397-0