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Amrish Gupta

TMS: Research




Introduction


Since the creation of the first transcranial magnetic stimulation (TMS) machine in 1985, the field of TMS research has grown exponentially. As more studies are published, the potentially life-changing benefits to patients with treatment-resistant psychiatric conditions, and the relatively rare side effects have become indisputable. In this article, I will discuss commonly prescribed treatments, outline what the research shows about the safety and efficacy of this TMS, and compare its benefits with those of different medications and therapies, as well as the different TMS systems available to patients today.


Common Psychiatric Treatments


Psychiatric disorders such as depression and anxiety are a major issue in our society, with some research suggesting that as many as 25% of adults in the UK will experience a mental health condition every year [1]. Even more alarmingly, these figures are believed to be growing, as shown by the 22% increase in mental health referrals in England since 2019 [2]. Many of these referrals will lead patients to different forms of therapy and medication, which certainly have the potential to bring relief to people suffering from a wide range of psychiatric conditions. However, these two common forms of treatment both have significant downsides. While traditional forms of talk therapy have been shown to be effective at reducing symptoms and teaching patients coping skills to deal with daily stressors [3], it can often be a long, arduous, and expensive process. Medications, on the other hand, have the potential to bring relatively quick results. Despite this, commonly prescribed medications also have a long list of potential side effects, many of which can be worse than the diagnosed condition. For example, selective serotonin reuptake inhibitors (SSRIs) such as citalopram and sertraline are the most commonly prescribed antidepressants in England [4]. The most common side effects of these medications include, but are not limited to: fatigue, nausea, sleep disturbance, loss of libido, weight-gain, and addiction. Furthermore, recent research has found that 20-60% of psychiatric patients are treatment resistant, meaning that their prescribed medication will have little-to-no effect and may require alternative treatments [5]. Luckily, many of these issues can be addressed by TMS.


TMS: Overview


TMS is a noninvasive treatment that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of several psychiatric disorders. It works by delivering electromagnetic pulses to specific areas of the brain, which can adjust brain activity and improve symptoms associated with conditions such as depression, anxiety, and OCD to name a few. One of the benefits that TMS has over traditional talk therapy is that patients often report symptom reduction within a few weeks of their first session, with others reporting improvements after just a few days [6]. When compared with traditional medication, TMS also has significantly fewer, and less frequent side effects [7]. Furthemore, TMS has been shown to be clinically effective at treating patients who have not responded to therapy and medications [8]. So, with such promising findings, let’s explore in depth what the wider literature has to say about the efficacy of this treatment.


TMS vs. Placebo


The best way to analyse the efficacy of a treatment is to test it against a placebo or sham treatment. For example, if researchers wanted to study the efficacy of a new blood pressure medication, they would split their study participants into 2 groups, one of which would receive the real medication and the other would receive an inert placebo drug with no active ingredients. This can tell researchers whether the treatment is genuinely effective, or if it just produces a placebo effect in which patients temporarily respond to treatment because of their belief that they are receiving a real medication. In the case of TMS, this involves researchers delivering subclinical stimulation, which is too weak to have any measurable effect on a patient’s symptoms.


One meta-analysis of 8 clinical trials found that patients with depression were over 3 times more likely to respond and almost 5 times more likely to achieve remission than patients in the placebo group [9]. These findings are supported by a more recent meta-analysis of 56 studies, which found that patients with depression were approximately 3.75 times more likely to respond to high-frequency TMS than to sham treatment [10]. Similar findings have been found for OCD patients, with TMS being shown to be significantly more effective than placebo in a meta-analysis of 26 studies [11]. Other analyses have found TMS to be almost 3 times more effective at reducing OCD symptoms than sham [12]. TMS has also been shown to be between 2 and 3 times more effective than placebo at reducing symptoms of bi-polar disorder [13,14]. From these findings we can conclude that TMS is significantly more effective at reducing symptoms of several psychiatric disorders than placebo or sham treatments.


TMS vs. Therapy


It can be difficult to compare the efficacy of TMS vs. traditional forms of psychotherapy such as CBT. There are not many studies in the wider literature that compare the 2 treatments as separate approaches. However, there are several studies that look at the response and remission rates in patients who receive clinical TMS treatment combined with psychotherapy, rather than psychotherapy alone. For example, a recent meta-analysis of 27 found that TMS combined with psychological interventions such as CBT and mindfulness, was significantly more effective at reducing psychiatric symptoms than psychological interventions alone [15]. These findings are supported by another recent analysis, which also highlighted the faster response rates of patients treated with TMS combined with psychotherapy than of those treated with psychotherapy alone [16]. These findings suggest that, when combined with TMS, the response and remission rates of psychological interventions such as CBT can be improved upon and even accelerated.


TMS vs. Medication


There have been several studies in recent years comparing the efficacy of TMS combined with medication vs. medication alone. For example, one study assessed the remission rates of depressed patients treated with a combination of high-frequency TMS and low-dose SSRIs against those treated with sham TMS and low-dose SSRIs. The findings showed that 35.3% of patients treated with active TMS and SSRIs achieved clinical remission, compared with 0% in the sham group [17]. These findings are supported by a meta-analysis of 29 studies, showing that a combination of TMS and medication to be more effective than medication alone at reducing symptoms of depression. Another recent study also found TMS treatment to be more cost-effective for patients than prescribed medication [18]. This research shows that not only is a combination of TMS and medication more effective at reducing negative symptoms than medication alone, but that TMS is also more cost-effective than prescribed medications.


H-Coil vs. F8-Coil


While the studies presented in this article highlight the safety and efficacy of TMS when compared with more common treatments such as psychotherapy and medication, there are also comparisons to be made between the different forms of TMS treatment. There are a number of different TMS systems available to patients, which use different treatment protocols and magnetic coils to provide stimulation. The most commonly used coil is known as the Figure-8 (F8) coil, which most TMS manufacturers use. However, there is a more advanced coil called the Hesed-coil (H-coil). The H-coil was patented by Brainsway and is used exclusively in Brainsway machines. The difference between these 2 coils is that the H-coil is able to stimulate deeper regions of the brain than the F8 coil, which is why H-coil TMS is often referred to as Deep TMS (dTMS). A recent meta-analysis and review of 19 studies found that H-coil TMS produced larger response and remission rates in patients with clinical depression than F8-coil TMS, with comparable rates of side effects [19]. These findings are corroborated by an indepent study showing that H-coil treatment reduced symptoms of depression in 59% of patients compared with 41% for F8-coil treatment. We can conclude from this research that while both forms of TMS are effective at treating clinical depression, the H-coil produces more significant benefits.


Conclusion


In summary, transcranial magnetic stimulation (TMS) emerges as a promising alternative for individuals grappling with treatment-resistant psychiatric conditions such as depression, anxiety, and OCD. Compared to traditional therapy and medication, TMS offers superior efficacy with fewer side effects. Meta-analyses consistently demonstrate TMS's superiority over placebo or sham treatments, affirming its genuine therapeutic impact. Moreover, when combined with psychotherapy or medication, TMS enhances treatment outcomes, suggesting its potential as an adjunctive therapy. Comparisons between TMS systems, particularly the F8-coil and the H-coil, indicate that the latter may offer superior benefits, especially in treating clinical depression. However, both forms of TMS exhibit efficacy, emphasising TMS's versatility and effectiveness in psychiatric treatment.




References


1. How common are mental health problems? (2020) Mental Health Facts and Statistics. Available at: https://www.mind.org.uk/information-support/types-of-mental-health-problems/statistics-and-facts-about-mental-health/how-common-are-mental-health-problems/ (Accessed: 08 February 2024). 


2. An NHS under Pressure - British Medical Association (2023) Mental Health Pressures in England. Available at: https://www.bma.org.uk/advice-and-support/nhs-delivery-and-workforce/pressures/an-nhs-under-pressure (Accessed: 08 February 2024). 


3. Cuijpers, P., Stingaris, A. and Wolpert, M. (2020) Treatment outcomes for depression: Challenges and opportunities, The Lancet Psychiatry. Available at: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30036-5/fulltext (Accessed: 08 February 2024). 


4. Lalji, H.M., McGrogan, A. and Bailey, S.J. (2021) An analysis of antidepressant prescribing trends in England 2015-2019, Journal of Affective Disorders Reports. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684293/ (Accessed: 09 February 2024). 


5. Howes, O.D., Thase, M.E. and Pillinger, T. (2021) Treatment resistance in psychiatry: State of the art and New Directions, Molecular Psychiatry. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960394/ (Accessed: 09 February 2024). 


6. Andre R. Brunoni, M. (2017) Repetitive transcranial magnetic stimulation for treatment of major depressive episodes, JAMA Psychiatry. Available at: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2594387 (Accessed: 09 February 2024). 


7. Chail, A. et al. (2018) Transcranial magnetic stimulation: A review of its evolution and current applications, Industrial psychiatry journal. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592198/ (Accessed: 09 February 2024). 


8. Gaynes, B.N. et al. (2021) Repetitive transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis, Psychiatrist.com. Available at: https://www.psychiatrist.com/jcp/repetitive-transcranial-magnetic-stimulation-treatment-2/ (Accessed: 09 February 2024). 


9. Berlim, M.T., Van den Eynde, F. and Jeff Daskalakis, Z. (2012) Clinically meaningful efficacy and acceptability of low-frequency repetitive transcranial magnetic stimulation (rtms) for treating primary major depression: A meta-analysis of randomized, double-blind and sham-controlled trials, Nature News. Available at: https://www.nature.com/articles/npp2012237 (Accessed: 09 February 2024). 


10. Barker, A.T. et al. (2018) Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and Bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials, Neuroscience & Biobehavioral Reviews. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0149763417309557 (Accessed: 09 February 2024). 


11. Öst, L.G. et al. (2021) Repetitive transcranial magnetic stimulation for obsessive-compulsive disorder: A meta-analysis of randomized, Sham-controlled trials, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. Available at: https://www.sciencedirect.com/science/article/abs/pii/S2451902221000872 (Accessed: 09 February 2024). 


12. Arns, M. et al. (2013) Repetitive transcranial magnetic stimulation (rtms) for obsessive–compulsive disorder (OCD): An exploratory meta-analysis of randomized and Sham-controlled trials, Journal of Psychiatric Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0022395613001192 (Accessed: 09 February 2024). 


13. Tee, M.M.K. and Au, C.H. (2020) A systematic review and meta-analysis of randomized sham-controlled trials of repetitive transcranial magnetic stimulation for bipolar disorder - psychiatric quarterly, SpringerLink. Available at: https://link.springer.com/article/10.1007/s11126-020-09822-6 (Accessed: 09 February 2024). 


14. Tavares, D.F. et al. (2017) Treatment of bipolar depression with deep TMS: Results from a double-blind, randomized, parallel group, Sham-controlled clinical trial, Nature News. Available at: https://www.nature.com/articles/npp201726 (Accessed: 09 February 2024). 


15. Xu, X. et al. (2023) Efficacy of repetitive transcranial magnetic stimulation (RTMS) combined with psychological interventions: A systematic review and meta-analysis of randomized controlled trials, MDPI. Available at: https://www.mdpi.com/2076-3425/13/12/1665 (Accessed: 09 February 2024). 


16. Adams, T.G.J. et al. (2022) Boosting psychological change: Combining non-invasive brain stimulation with psychotherapy, Neuroscience & Biobehavioral Reviews. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0149763422003566 (Accessed: 09 February 2024). 


17. Blumberger, D.M. et al. (2018) Alternate day DTMS combined with ssris for chronic treatment resistant depression: A prospective Multicenter Study, Journal of Affective Disorders. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0165032717324564 (Accessed: 09 February 2024). 


18. Blumberger, D.M. et al. (2023) Cost-effectiveness analysis comparing repetitive transcranial magnetic stimulation therapy with antidepressant treatment in patients with treatment-resistant depression in Japan, Psychiatry Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0165178123005231#:~:text=Previous%20cost%2Deffectiveness%20analyses%20of,and%20even%20reduces%20medical%20costs. (Accessed: 09 February 2024). 


19. Gellersen, H.M. and Kedzior, K.K. (2019) Antidepressant outcomes of high-frequency repetitive transcranial magnetic stimulation (rtms) with f8-coil and deep transcranial magnetic stimulation (dtms) with H1-coil in Major Depression: A systematic review and meta-analysis - BMC Psychiatry, SpringerLink. Available at: https://link.springer.com/article/10.1186/s12888-019-2106-7 (Accessed: 09 February 2024). 


20. Carlo, V.D. et al. (2019) Efficacy of repetitive transcranial magnetic stimulation using a figure-8-coil or an H1-coil in treatment of major depressive disorder; a randomized clinical trial, Journal of Psychiatric Research. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0022395619300081 (Accessed: 09 February 2024).


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