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Transcranial magnetic stimulation for the treatment of psychosocial conditions

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FOI 24/25- 0013 DOCUMENT 34

Transcranial magnetic stimulation for the treatment of psychosocial conditions

The content of this document is OFFICIAL. Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters, they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Research question: What is the efficacy of Transcranial Magnetic Stimulation for adults with Obsessive Compulsive Disorder, Bipolar Disorder and/or Depression? Is there evidence of impact on functional outcomes such as social and economic participation? Date: 23/06/2023 Requestor: Jillian redacted: s22(1)(a)(ii) - irrelevant material Endorsed by: Katrin redacted: s22(1)(a)(ii) - irrelevant Researcher: Aaron redacted: s22(1)(a)(ii) - irrelevant material Cleared by: Stephanie redacted: s22(1)(a)(ii) - irrelevant material

1. Contents

Transcranial magnetic stimulation for the treatment of psychosocial conditions …………………… 1

  1. Contents ……………………………………………………………………………………………………….. 1
  2. Summary ………………………………………………………………………………………………………. 2
  3. Transcranial Magnetic Stimulation …………………………………………………………………….. 2
  4. Guidelines ……………………………………………………………………………………………………… 3
  5. Major Depressive Disorder ………………………………………………………………………………. 4
  6. Bipolar disorder ………………………………………………………………………………………………. 5
  7. Obsessive-Compulsive Disorder ……………………………………………………………………….. 5
  8. References ……………………………………………………………………………………………………. 6

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2. Summary

Transcranial Magnetic Stimulation (TMS) is a type of non-invasive brain stimulation. There is a substantial body of literature relating to use of repetitive TMS (rTMS) to treat many psychiatric and neurological disorders. This paper focusses on Major Depressive Disorder (MDD), bipolar disorder and Obsessive-Compulsive Disorder (OCD).

Most clinical practice guidelines and systematic reviews agree that rTMS is an effective treatment for symptoms of depression, especially treatment resistant Major Depressive Disoder (MDD). There is still some debate regarding treatment protocols and effect sizes.

While there is evidence that rTMS can be effective for bipolar disorder and OCD, it is more tentative than in the case of MDD. The treatment may be offered in these cases where other treatments have not been successful. There is wide agreement in the research that heterogeneity of treatment protocols and small sample sizes in primary studies make it difficult to draw more definite conclusions.

Evidence of improvements in functional outcomes for MDD, bipolar and OCD is minimal. Some evidence exists around cognitive function. There is some evidence that rTMS can improve cognitive function in healthy people as well as people with psychosocial conditions. However, more evidence is required to establish this. No experimental evidence relating to efficacy of rTMS to improve social or economic participation was found.

3. Transcranial Magnetic Stimulation

TMS is a type of non-invasive brain stimulation, which is a variety of neuromodulation or neurostimulation. rTMS is generally safe and well-tolerated by patients and patients are conscious during treatment. TMS involves the application of a wire coil to the patient’s head which sends a pulsed magnetic field through the skull into the brain to alter brain function (RANZCP, 2018a; RANZCP, 2018b; Hyde et al, 2022; Moses et al, 2023).

Single-pulse or paired-pulse TMS involves delivering one or two pulses to the patient’s brain and is used primarily for exploratory or diagnostic purposes. Repetitive TMS is used for therapeutic purposes and involves delivering recurring pulses to a specific brain region to induce changes in brain activity. (Mann & Malhi, 2023; Klomjai et al, 2015).

Most research has focussed on rTMS for the treatment of depression but there is a substantial literature base describing its use for other psychiatric disorders, neurological and neurodevelopmental disorders, movement disorders, epilepsy, chronic pain and tinnitus (Tikka et al, 2023; Mann & Malhi, 2023; Moses et al, 2023; Hyde et al, 2022; Lefaucher et al, 2020).

Protocols for rTMS can vary by:

  • length or number of sessions frequency during a treatment block
  • frequency, intensity, duration, or pattern of stimulus
  • brain region targeted

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  • coil-type or other device parameters
  • additional or simultaneous treatments (Gutierrez et al, 2022; Klomjai et al, 2015).

Recognised varieties of rTMS include:

  • theta-burst stimulation (TBS) –uses multiple bursts of high frequency stimulation over a shorter session (Voigt et al, 2021)
  • accelerated TMS (aTMS) – treatment sessions are scheduled multiple times per day over a shorter overall treatment period (Somnez et al, 2019)
  • deep TMS (dTMS) –uses a specialised coil to deliver pulses to deeper brain regions (Gutierrez et al, 2022)
  • priming TMS (pTMS) – a sub-threshold stimulus is delivered with the intention of making the brain region more receptive to subsequent treatment (Lee et al, 2021).

4. Guidelines

Professional Practice Guidelines from the Royal Australian and New Zealand College of Psychiatrists (RANZCP) supports the use of rTMS for depression, especially treatment resistant depression and as a treatment of auditory hallucinations in schizophrenia (RANZCP, 2018a; RANZCP, 2018b).

Further evidence has emerged since the publication of the RANZCP guidelines. 2020 clinical guidelines from a European team of clinicians notes definite efficacy of rTMS for depression and probable efficacy for its use in treating PTSD, auditory hallucinations and negative symptoms of schizophrenia. These guidelines note only possible efficacy for treatment of OCD (Lefaucher et al, 2020).

A clinical practice guideline jointly published by the U.S. Department of Veterans Affairs and U.S. Department of Defense recommends TMS for treatment resistant MDD, but notes only weak evidence in its favour (McQuaid et al, 2022).

Recent clinical guidelines from the Indian Psychiatric Society offer a strong recommendation for the use of high frequency rTMS to treat acute episodes of depression. They offer moderate or low strength recommendations for the use of rTMS to treat bipolar disorder, generalised anxiety disorder, OCD, post-traumatic stress disorder, negative symptoms of schizophrenia, nicotine use disorder, Alzheimer’s disease, insomnia, migraine, fibromyalgia and tinnitus (Tikka et al, 2023).

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5. Major Depressive Disorder

Clinical practice guidelines and systematic reviews generally support TMS as a safe and effective treatment for MDD. Evidence is strongest for the efficacy of high frequency rTMS on acute depressive episodes (Tikka et al, 2023; Hyde et al, 2022; Lefaucher et al, 2020) and treatment resistant depression (McQuaid et al, 2022; RANZCP, 2018b).

Brini et al (2022) reviewed 29 systematic reviews including 15 meta-analyses of TMS efficacy for patients with MDD. They found authors of all studies agreed that TMS is effective for reducing depressive symptoms of MDD. However, the authors conclude that TMS may be less efficacious and less well tolerated than current literature suggests. After reviewing meta-analyses, Brini et al found that the effect sizes were generally smaller than reported. They also report that systematic reviews included in the study are mostly of very low quality and show high risk of bias. Primary studies included in the reviews also show a high level of heterogeneity in treatment protocols.

There is evidence of improved cognitive function after TMS in people with MDD, including executive function, set-shifting ability, visual scanning, and psychomotor speed (Xu et al 2023; Torres et al, 2023; Tateishi et al, 2022; Struckman et al, 2021; Schaffer et al, 2020; Martin et al, 2017). Begeman et al (2020) found only small improvements in working memory and attention. Tikka et al (2023) note that if a patient’s depressive symptoms respond to TMS, it is more likely they will see improvements in executive function as well.

Very few studies report on other functional outcomes of TMS treatments. A Canadian health technology assessment offers some qualitative evidence that rTMS treatment improves patient’s quality of life:

When it came to the nature of the improvement, participants often described the lifting of a weight off their shoulders and the disappearance of negative thoughts. Often activities of daily living were easier to do and could be done with greater energy. Some participants mentioned a change in sleep pattern or greater appetite (Ontario Health, 2021, p.119)

The same report conducted a systematic review of 68 studies and found only one that reported functional outcomes (Taylor et al, 2018). Another government funded Canadian review identified Taylor et al (2018) as the only study reporting functional outcomes (Pohar & Farah, 2019). This RCT assessed efficacy of rTMS on 32 people with MMD. The Work and Social Adjustment Scale (WSAS) and the Global Assessment of Function (GAF) were used as secondary outcome measures. The study found no significant effect on either WSAS or GAF scores after rTMS treatment (Taylor et al, 2018).

One large observational study of 257 people with treatment resistant MDD found a significant improvement in function following rTMS treatment using the Clinical Global Impressions survey (CGI-S). The effect was maintained at 3, 6, 9 and 12 month follow ups (Denner et al, 2014).

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6. Bipolar disorder

Mutz (2023) and Tikka et al (2023) note evidence that TMS is effective in treating bipolar disorder using high frequency stimulation of the dorsolateral prefrontal cortex. However, numerous other studies find no significant effect compared to sham controls. Researchers conclude that further research is needed to determine if TMS is effective in treating bipolar (Mutz, 2023; Hyde et al, 2022; Elsayed et al, 2022; Hett & Marhawa, 2020; Gold et al, 2019).

Mutz et al (2023) report evidence from 2 studies indicating improvement in cognitive function after TMS. An RCT assessing 52 people with bipolar disorder found improve across all cognitive measures compared to sham control. A pilot study assessing 16 people with bipolar disorder found improvements in verbal learning but no other cognitive functions. However, more studies reviewed found no significant effect (Mutz et al, 2023; Hett & Marhawa, 2020).

No other information on functional outcomes was found.

7. Obsessive-Compulsive Disorder

Recent systematic reviews note general positive results from studies investigating effects of TMS on symptoms of OCD, especially low frequency stimulation of the dorsolateral prefrontal cortex or supplementary motor area. However, reviewers also uniformly cite small sample sizes, inconsistent results and heterogeneity of treatment protocols as factors reducing confidence in any positive recommendations (Tikka et al, 2023; Hyde et al, 2022; Fitzimmons et al, 2022; Pellegrini et al, 2022; Yu et al, 2022; Liang et al, 2021; Lefaucher et al, 2020; Rapinesi et al, 2019). Liang et al (2021) observe that despite evidence of efficacy, research into the effect of TMS on OCD still requires adequately sized and controlled studies.

Rapinesi et al suggest rTMS may be a suitable treatment for patients who do not respond to pharmacological treatment. This is echoed in the 2017 OCD clinical practice guidelines from the Indian Psychiatric Society, which suggests TMS only after multiple unsuccessful medication trials (Janardhan Reddy et al, 2017). In contrast, Pellegrini et al (2022) find that rTMS is most effective in patients not resistant to medication or who have had only one unsuccessful medication trial. They therefore recommend TMS earlier rather than later in the treatment pathway.

Fitzimmons et al (2022) and Yu et al (2022) note large and significant improvements in CGI-S after rTMS, indicating likelihood of some functional improvement in patients. No other information on functional outcomes was found.

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8. References

Begemann, M. J., Brand, B. A., Ćurčić-Blake, B., Aleman, A., & Sommer, I. E. (2020). Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis. Psychological medicine, 50(15), 2465–2486. https://doi.org/10.1017/S0033291720003670

Dunner, D. L., Aaronson, S. T., Sackeim, H. A., Janicak, P. G., Carpenter, L. L., Boyadjis, T., Brock, D. G., Bonneh-Barkay, D., Cook, I. A., Lanocha, K., Solvason, H. B., & Demitrack, M. A. (2014). A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period. The Journal of clinical psychiatry, 75(12), 1394–1401. https://doi.org/10.4088/JCP.13m08977

Elsayed, O. H., Ercis, M., Pahwa, M., & Singh, B. (2022). Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions. Neuropsychiatric disease and treatment, 18, 2927–2943. https://doi.org/10.2147/NDT.S273503

Fitzsimmons, S. M. D. D., van der Werf, Y. D., van Campen, A. D., Arns, M., Sack, A. T., Hoogendoorn, A. W., other members of the TETRO Consortium, & van den Heuvel, O. A. (2022). Repetitive transcranial magnetic stimulation for obsessive-compulsive disorder: A systematic review and pairwise/network meta-analysis. Journal of affective disorders, 302, 302–312. https://doi.org/10.1016/j.jad.2022.01.048

Hett, D., & Marwaha, S. (2020). Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder. Therapeutic advances in psychopharmacology, 10, 2045125320973790. https://doi.org/10.1177/2045125320973790

Hyde, J., Carr, H., Kelley, N., Seneviratne, R., Reed, C., Parlatini, V., Garner, M., Solmi, M., Rosson, S., Cortese, S., & Brandt, V. (2022). Efficacy of neurostimulation across mental disorders: systematic review and meta-analysis of 208 randomized controlled trials. Molecular psychiatry, 27(6), 2709–2719. https://doi.org/10.1038/s41380-022-01524-8

Gold, A. K., Ornelas, A. C., Cirillo, P., Caldieraro, M. A., Nardi, A. E., Nierenberg, A. A., & Kinrys, G. (2019). Clinical applications of transcranial magnetic stimulation in bipolar disorder. Brain and behavior, 9(10), e01419. https://doi.org/10.1002/brb3.1419

Gutierrez, M. I., Poblete-Naredo, I., Mercado-Gutierrez, J. A., Toledo-Peral, C. L., Quinzaños-Fresnedo, J., Yanez-Suarez, O., & Gutierrez-Martinez, J. (2022). Devices and Technology in Transcranial Magnetic Stimulation: A Systematic Review. Brain sciences, 12(9), 1218. https://doi.org/10.3390/brainsci12091218

Janardhan Reddy, Y. C., Sundar, A. S., Narayanaswamy, J. C., & Math, S. B. (2017). Clinical practice guidelines for Obsessive-Compulsive Disorder. Indian journal of psychiatry, 59(Suppl 1), S74–S90. https://doi.org/10.4103/0019-5545.196976

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Klomjai, W., Katz, R., & Lackmy-Vallée, A. (2015). Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS). Annals of physical and rehabilitation medicine, 58(4), 208–213. https://doi.org/10.1016/j.rehab.2015.05.005

Lee, J. C., Corlier, J., Wilson, A. C., Tadayonnejad, R., Marder, K. G., Ngo, D., Krantz, D. E., Wilke, S. A., Levitt, J. G., Ginder, N. D., & Leuchter, A. F. (2021). Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Brain stimulation, 14(4), 1015–1021. https://doi.org/10.1016/j.brs.2021.06.008

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Martin, DM, McClintock, SM, Forster, J, Lo, TY, Loo, CK. (2017). Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects. Depression and Anxiety. 34: 1029–1039. https://doi.org/10.1002/da.22658

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